Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biochem - YEAR 2 > Semester 1 > Flashcards

Semester 1 Flashcards

1
Q

What contains 2 fatty acids, a glycerol and a phosphdiester bond?

A

Phosphatidyl Serine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is NOT a key feature of cholesterol?

A

It is responsible for determination of ABO blood groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the key features of cholesterol?

A

It is utilised to synthesise bile acids involved in digestion
It contains a steroid ring
It anchors proteins within plasma membrane (lipid raft)
It is a precursor for steroid hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What explains why cholesterol controls the fluidity of the plasma membrane?

A

Separates hydrocarbon chains of phospholipids in the plasma membrane so that they cannot interact and become more rigid.
Rigid structure works like bookends

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which part of cholesterol might enable it to be considered as amphipathic?

A

Hydroxyl group

This group has unequal sharing of electrons so generates a slight + / - end to covalent bond leading to interaction with H20 molecules = soluble in water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What effect does increasing cholesterol concentration within cell membrane have on membrane fluidity?

A

Increase in fluidity!

Because it immobilises the first 1/3 of phospholipid molecule due to interaction between FA tails and steroid ring structure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are components of a cell membrane?

A

Phosphatidyl ethanolamine
Glycolipids
Glycoproteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the role of the plasma membrane?

A

Create a semi permeable and dynamic barrier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What explains the meaning of ‘Cholesterol is amphipathic’?

A

Polar head and rings interact with similar phospholipid regions

OH group interacts with phospholipid heads and the rest of the molecule with fatty acid tails

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

HMG CoA reductase is the rate limiting enzyme in cholesterol synthesis.
What affects its action?

A

High cellular cholesterol levels due to uptake of LDL from blood.

Cellular levels of LDL ^ after uptake by endocytosis leads to ^ HMG CoA reductase degradation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is correct about lipid rafts?

A

They keep protein subunits together

Can also keep them apart to avoid overactivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Under what circumstances might something need to cross the cell membrane by diffusion?

A

Something produced in cell e.g steroid hormones and fat soluble vitamins

To get rid of waste products

If cell is infected by a pathogen / cancerous - need to get a drug across the membrane! (Needs to be lipophilic therefore, quickest method is diffusion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What principles govern free movement across the membrane?

A

Molecular weight - less than 500 Da
Needs to be lipid if moving by diffusion, if not lipid based then it needs a carrier or channel protein
High concentration outside and low concentration inside membrane for diffusion
No more than 5 hydrogen bond donors and no more than 10 acceptors
Low overall charge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why do bacteria such as E Coli do NOT have cholesterol in their cell membrane?

A

Because they have a cell wall! It is the first like of defence
It acts like a cell membrane does in mammalian cells - they need cholesterol for fluidity and rigidity otherwise membrane would be disrupted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is an antibody and what are the parts of it?

Which part of the antibody binds to Specific sequence?

A

A Y-shaped protein produced by B cells / B lymphocytes. The mature B lymphocytes called plasma cells.

The variable regions (heavy or light) are specific to the antigen -in every case will recognise a different protein.

Fab regions are specific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is fluorescence?

How do we detect fluorescence?

A

It’s a type of electromagnetic radiation usually in form of light that’s caused by exciting a source. You give it energy and it emits light at a slightly different frequency.
Needs a constant stimulation / energy.

Use detector at specific wavelength

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do we visualise the binding of antibodies to their target?

A

Have spectrum from purple - red of visible light.
Dyes are used attached to end of antibody and are excited by specific wavelength
E.g Alexa 568 is excited at 568nm BUT it emits light closer to 580nm so detector will need to detect 580nm.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does amphipathic mean?

A

Part of the molecule is hydrophilic and another part is hydrophobic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does conjugation mean?

A

Formation of a link between an amino acid and a waste or toxic product

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does emulsification mean?

A

The mixing of 2 liquids that are usually unmixable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does hydrophilic mean?

A

Attracted to Aqueous substances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does hydrophobic mean?

A

Attracted to fats

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What does hydrogen bond mean?

A

Intermolecular force that forms dipole dipole attraction when hydrogen atom bonded to strongly electronegative atom exists in vicinity of another electronegative atom with lone pair of electrons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does cholestasis mean?

A

Decreased flow of bile due to impaired secretion by hepatocytes or obstruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What does polar mean?

A

A molecule where the distribution of electrons between covalently bonded atoms is NOT even causing a slight negative and positive charge to that atom

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is a steroid?

A

Lipid containing a 4 ringed ridged structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is a disulphide bridge / bond?

A

A reaction between sulfhydryl side chains of 2 cysteine residues
One S anion acts as a nucleophile attacking the side chain of a 2nd cysteine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is a lipoprotein?

A

Any group of soluble proteins that combine with and transport fat or other lipids in the blood plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the log P value?

A

A measure of the preference of a compound to dissolve in either water or an organic solvent (such as Octanol) when uncharged

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is a ligand?

A

A molecule or ion that binds to another (usually larger) molecule causing a change in function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does de novo mean?

A

Newly generated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is a lipid raft?

A

Dynamic assemblies of proteins and lipids that float freely within the bilayer of the plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is a Michelle?

A

Roughly spherically shaped grouping of amphiphillic molecules contained in a liquid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How does cholesterol effect fluidity for saturated and unsaturated fatty acids?

A

Saturated - cholesterol decreases fluidity

Unsaturated - cholesterol increases fluidity, pushes FA apart because of 30 degree kink in tail

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What type of secondary structure of protein are necessary for the generation of large channel proteins?

A

Beta pleated sheets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Membrane proteins can be attached to the phospholipid bilayer by a fatty acid chain.
What is the reason for this?

A

Maintain the presence of the protein close to a transmembrane protein within a lipid raft.
This can enhance cellular signalling and the protein may be present on either side of the membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What properties does transmembrane proteins possess?

A

N- or C- terminal ends of the protein contain amino acids that mediate protein protein interactions that will allow the accessory protein to support ligand binding.

Protein protein interactions will enable shape stabilisation or a change that enables ligand binding. Accessory proteins are usually tethered to the membrane by carbohydrate linkers.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is essential for the interaction with the extracellular matrix.

A

Glycoprotein

E.g. proteoglycans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Lipoproteins are a … molecule with a layer of phospholipids around the … also containing …
In the centre you’ve got cholesterol esters and …
In the outer membrane you’ve got an … which is essential for … to work.

A

Spherical
Outside
Cholesterol
Triglycerides
Apolipoprotein
Lipases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

One of Lipinski’s rule of 5 is High lipophicility (expressed as p value less than 5)
What is this an estimate of?

A

Used as an estimation of the molecules ability to passively diffuse across the lipid membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What causes the ‘kink’ in unsaturated fatty acids?

A

The carbon carbon double bond induces a 30 degree bend which is known as the kink.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are liver cells called?

What organelles are important for metabolic activity?

What organelles are important for removing waste products?

A

Hepatocytes

Mitochondria

Smooth ER - contains enzymes required for detoxification.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

The plasma membrane has a high fluidity and few van der waals forces, but why is it thin?

A

Saturated long chain fatty acid tails extend longer than unsaturated with the 30 degree kink, and therefore membrane is thinner.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

The … synthesis of cholesterol takes place in the … using acetyl CoA together with the enzyme … which serves as the rate limiting step

A

De novo
Liver
HMG CoA reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Bile acids are integral to the metabolism of …
Due to their … nature they can solubilise hydrophobic fats by forming small fat droplets known as …
This is known as … and significantly increases the surface area that … can work on.

A

Dietary fats
Amphiphilic
Micelles
Emulsification
Intestinal lipases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What are the differences between flow cytometry and confocal microscopy?

A

Cells going in the flow cytometer can be in a suspension WHEREAS those on the microscope slide need to be attached or squashed on to the microscope slide.

Means blood cells are perfectly suited to analysis by flow cytometry: erythrocytes, leukocytes, lymphocytes. They are already in a suspension!

Confocal microscope: much more detailed, can actually see the structures. But it is only qualitative.

Confocal microscope can tell if target is on top, bottom, inside or outside cell. Can’t tell that with cytometer.

In common: both need lasers and detectors

Analysis of cells: slow process in microscope. With cytometer takes a few seconds to analyse a thousand cells! Much faster.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How does the membrane change during apoptosis? And it’s integrity ad a result of this?
Apoptosis = programmed cell death

A

Membrane blebbing - tiny accidental pinching off of the membrane (loss). Cytosol is in there too as well as some nuclear content maybe if nucleus isn’t functioning.

Shrinking of the nucleus and organelles

Phosphatidylserine on outside - would change charge of cell membrane

Condensation of chromatin, nucleus

Vast amount of calcium in cytoplasm, KEY as it turns on scramblase which allows phos. Serine to be on outside of cell. Scramblase only enzyme active at this point!

Loss of integrity = disintegration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is flow cytometry?

A

A multi parametric analysis tool, uses lasers and detectors. Signals are converted into electrical signals. Computer analysis

Uses a cell suspension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are the advantages / disadvantages of flow cytometry vs confocal microscopy?

A

Provides faster analysis, accurate (as long as it is a single cell at a time), quantitative, less human error

Expensive, less detailed, prone to technical problems, can’t see qualitative picture of cell, needs specialised operator

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Examples of signalling pathways

A

Caspases cascade (proteolytic cascade)

Any homeostatic mechanism - anything with a feedback mechanism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How can we ensure transmission is effective for cell signalling?

A

Lipid raft to keep things close together and parts that are not needed separate

Support around receptor to receive signalling:
Scaffolding
Complex formation
Docking sites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What are the 4 common intracellular secondary messengers?

A

Cyclic AMP - activates protein kinase A

Cyclic GMP - activates protein kinase G and opens cation channels in rod cells

DAG - activates protein kinase C

IP3 - opens Ca2+ channels in ER > Ca2+ levels increase > nearby proteins activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

To respond to a signal, a cell must have a… molecule that can defect the signal

A

Receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

A molecule that binds to the particular 3D structure of a receptor is known as what?

A

Ligand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

When a protein, amino acid or peptide ligand binds to its specific receptor…

A

A second messenger molecule is activated

Intracellular proteins form a cascade of events that lead to generation of secondary messengers cAMP, cGMP, IP3 or DAG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

When are G proteins active?

A

When GTP is bound

When GTP is bound there is a change in shape that enables the breakup of a, b and y subunits to disassemble from one another and be present in an active form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is FALSE about plasma membrane G protein receptor signalling?

A

G protein alpha subunit Ga is inactive when bound to GTP

the binding of GTP to the a subunit needs to happen for it to become activated!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Why do some ligands trigger a second message?

A

The first messenger cannot cross the membrane!

For the message to be passed on there is a need for participants of the cascade on both sides of the membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What type of receptor catalyses phosphorylation of target protein?

A

Kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

ALL cell signalling involves which of the following?

A

A change in receptor shape

Shape change happens regardless of ligand, receptor type or otherwise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Steroid hormones activate a cell by what mechanism?

A

Binding to a receptor within the cell CYTOPLASM

Steroid hormones are synthesised from cholesterol, containing the ridged sterol ring structure
So are able to move across the cell membrane WITHOUT needing to be transported by a protein or move through a channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Ligand gated ion channels are specific for which of the following?

A

The ligand and the ion type

The ligand must bind specifically to the receptor and the channel will only allow specific ions through depending on the selectivity filter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Not all cells respond to a given endocrine signal because…

A

They do not have a specific receptor for the signal

The receptor as a detector is required otherwise the cell does not know what the signal means!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Hormones cause multiple responses by…

A

Using multiple receptors

Causing different cellular responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What hormone is NOT derived from cholesterol?

A

Adrenaline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What is a primary bile acid example?

A

Cholic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is required for the movement of phospholipids between inner and outer leaflet of plasma membrane?

A

ATP

Flippase and floppase use ATP to move phospholipids between leaflets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What does Annexin V bind to?

A

Phosphatidyl serine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Flow cytometry graph: cells in the lower right quadrant are in early apoptosis
What does this tell you?

A

Annexin V staining indicates phosphatidyl serine is present on surface but ATP is still being generated so propidium iodide is still being exported from cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What is the role of Scramblase in programmed cell death known as apoptosis?

A

It is activated by Ca2+ and exports phosphatidyl serine to outer leaflet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Which of the coloured coat proteins represents Clathrin?

A

Green

Clathrin is used for bud formation from the Golgi moving to early endosome and lysosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What is the role of scramblase at the plasma membrane?

A

It moves phospholipids between the inner and outer leaflet of a phospholipid bilayer in an indiscriminate manner

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Propidium iodide is a vital step detected by fluorescence flow cytometry
In live cells…

A

It is excluded in an ATP dependant manner by intact membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What is cleavage?

A

The splitting or severing of something

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What are GTPases?

A

Enzymes that catalyse the hydrolysis of GTP guanosine triphosphate to GDP guanosine diphosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What is a kinase?

A

Proteins that generally add a phosphate (PO42 also known as phosphoryl groups) to proteins at specific amino acids

Eg. Serine kinases add phosphate groups at serine amino acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What are phosphatases?

A

An enzyme that removes a phosphate group from a protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What is phosphorylation?

A

The addition of a phosphate PO42- to molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

What is a receptor?

A

A molecule in the cell membrane which responds specifically to a particular signal (ligand)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What is a structural motif?

A

Short segments of protein 3D structure which are spatially close but not necessarily adjacent in the sequence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What methods could we use to fura 2 dye with?

A

Flow cytometry
Fluorescence
Confocal microscopy
Spectrophotometry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

The liver has got large volumes of… not only because the ER is the place where you generate … but also because it is the house for all those metabolic enzymes that are going to start … components which is a key … of the liver

A

Endoplasmic reticulum
Lipids
Detoxifying
Function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Erythrocytes needs to be able to move around the body at high speeds, therefore they need strength in their …
They have an ankyrin and spectrin … behind them and large volumes of … because they need to have lipid rafts for the mesh to … through those band 3 proteins into the membrane.

Hepatocytes do not have large volumes of cholesterol in them because they need a nice … membrane as they don’t need to move fast around body. They require a lot more … in the membrane I.e. protein channels with a selectivity filter. Needs things in membrane that regulate …

A

Membrane
Mesh
Cholesterol
Attach
Fluid
Proteins
Movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Foregut metabolisers (eg cows) have bacteria in the foregut that convert glucose into volatile fatty acids.
What are the potential advantages?

A

The bacteria produce vitamins and amino acids that the cow can utilise

The cows foregut contains bacteria that secret Cellulase

The bacteria can remove toxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What tissue stores Glycogen and uses it to maintain normal blood glucose levels in the fasting phase?

A

Liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Foregut metabolisers (eg cows) have bacteria in the foregut that metabolise cellulose and glucose. What is the main DISadvantage for the cow?

A

The cows have to convert the volatile fatty acid (products of the bacterial glucose metabolism) into glucose via gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

The erythrocytes produce lactate. Why?

A

They lack mitochondria, therefore cannot undertake aerobic glycolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

The monosaccharide Sorbitol is converted into Fructose by the enzyme…

A

Sorbitol dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What compounds contain alpha 1-6 glycosidic bonds?

A

Glycogen

Amylopectin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What is an example of an Antiport System?

A

Na+ K+ ATPase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

What glucose transporter is reversible?

A

GLUT 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Anaerobic metabolism of glucose is important under what conditions?

A

Anaerobic bacteria

Exercising muscle (oxygen limitation)

Hypoxia (humna, eg heart attack)

Ethanol metabolism (yeast)

Some cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Uptake of glucose from the intestinal lumen (under conditions where glucose concentrations in the lumen are low) requires energy.
What drives this process?

A

Electrical potential

Na+ K+ ATPase

Chemical potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What glucose transporter is found in the endoplasmic reticulum?

A

GLUT 7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

What glucose transporter is activated by Insulin action?

A

GLUT 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

Humans CANNOT digest cellulose because…

A

The intra molecular hydrogen bonds in cellulose make it water insoluble

Cellulose contains Beta 1-4 glycosidic bonds

They lack Cellulase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

What tissues can store glycogen?

A

Liver

Skeletal muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

The enzyme pyruvate kinase is the FINAL control point in glycolysis. Why is this beneficial?

A

Want to prevent a futile cycle because it utilises energy! (Useless)

Cycle: pyruvate > oxaolacetate, activated by hormone glucagon.
Oxaloacetate > PEP is activated by hormone glucagon.

PEP > pyruvate controlled by hormone insulin! If we REMOVE this step, we remove the futile cycle! Which is why pyruvate kinase is the final control point!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Pathophysiology of type 1 diabetes mellitus

A

Autoimmune insulitis

Inflammation more aggressive in young children than adults

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Epidemiology of type 1 diabetes mellitus

A

Most common form of diabetes in children

Continues to present through decades but submerged by incidence of type 2 diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

How can you differentiate between the major types of diabetes mellitus?

A

Clinical features

Islet cell antigen autoantibody titres gradually wane

Type 1 diabetes genetic risk score

Assess endogenous insulin secretion by testing C peptide in people using insulin therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

What are symptoms of new onset Type 1 diabetes mellitus?

A

Collapsed, previously well
Severely dehydrated
Confused
Short of breath but normal arterial pO2

K+ levels increased

Glucose levels increased = diabetic

B OH butyrate levels increased = keto

pH levels decreased = acidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Pathophysiology of type 2 diabetes

A

Insulin resistance

Pancreatic beta cells respond but not enough…

And high blood glucose gradually damages them!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Autoimmune insulitis in type 1 diabetes differs with …

A

age of onset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

What is diabetes mellitus?

A

Osmotic diuresis secondary to excessive blood glucose concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

What is type 1 diabetes mellitus?

A

Autoimmune destruction of pancreatic beta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

What is type 2 diabetes mellitus?

A

Insulin resistance leading to beta cell fatigue and gradual failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Islet cell antigen auto antibody positivity … gradually

A

Wanes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

Normal and abnormal blood glucose concentrations are…

A

Tightly controlled

Insulin secretion responds rapidly to requirements in healthy individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

Endogenous vs exogenous insulin

A

Modifications to alter absorption and clearance allow approximately physiological replacement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

Diabetic keto acidosis pathophysiology

A

Absolutely insulin deficiency = profound lipolysis, gluconeogenesis and glycogenolysis

Oxaloacetate consumed by gluconeogenesis, Acetyl CoA diverted from Krebs cycle

Osmotic diuresis and metabolic acidosis induced gastrointestinal loss cause dehydration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Hypoglycaemia

A

Whipple’s triad definition stretches beyond diabetes mellitus

Much higher risk of hypoglycaemia in type 1 diabetes compared with other types of diabetes

No endogenous insulin to switch off, glucagon response lost!

Frequent exposure lowers threshold for adrenaline release = impaired awareness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

What is the level 1 hypoglycaemia definition?

A

Glucose < 4 mmol/ L = usually no need to report

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

What is the level 2 hypoglycaemia definition?

A

Glucose <3 mmol/L = serious, clinically important hypoglycaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

What is the level 3 hypoglycaemia definition?

A

SEVERE hypoglycaemia = severe cognitive impairment requiring external assistance for recovery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

Basal secretion

A

Low concentration

Persists during fasting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

Prandial secretion

A

Rapid

Proportional to requirements

Change in concentration sometimes order of magnitude or greater

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Endogenous insulin forms a hexamer around a Zn2+ ion

A

Hexamers dissociate into dimers

Dimers dissociate into monomers

Monomers are the active form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

Endogenous insulin secretion enters the liver …

A

Directly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

Exogenous insulin is … before entering target organs

A

Diluted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

In type 1 diabetes, mimicking … insulin secretion is difficult

A

Normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

What are the rapid acting insulin analogues?

A

Insulin lispro

Insulin aspart

Insulin glulisine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

What is neutral protamine hagedorn (NPH)?

A

5:1 human sequence insulin: protamine and zinc

Protamine stabilises insulin crystals

Injected as a suspension

Thorough mixing essential prior to administration

Absorbed slowly from subcutaneous depot

High dose to dose variability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

What is the long acting insulin analogue that precipitates?

A

Insulin glargine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

What are the long acting insulin agonists that bind to albumin?

A

Insulin detemir

Insulin degludec

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

What is the route of endogenous insulin?

A

Hepatic portal vein > liver > ACTION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

What is the route of exogenous insulin?

A

Systemic veins > pulmonary circulation > dilution > liver > ACTION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

Human insulin forms:

A

Hexamers > dimers > monomers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

Rapid acting insulin analogues are …

A

Monomeric

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

Long acting insulin’s exhibit delayed … and + or - clearance from blood

A

Absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

Dose to dose variation in effect is …

A

Undesirable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

Diagnosing diabetic keto acidosis : symptoms?

A

Lethargy
Weakness
Vomiting
Abdominal pain
Confusion
Coma
Kussmaul respiration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

Diagnosing diabetic keto acidosis:

A

Ketonaemia >3 mmol/L or significant ketonuria (more than 2+ on standard urine sticks)

Blood glucose > 11 mmol/L or known diabetes mellitus

Serum bicarbonate <15 mmol/L and or venous pH <7.3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

Diabetic keto acidosis treatment priorities:

A
  1. Correct dehydration - intravenous fluids
  2. Switch off keto genesis - intravenous insulin
  3. Prevent life threatening hypokalaemia - add potassium to intravenous fluid
  4. Prevent it happening again - identify cause, correct and educate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

What is whipples triad?

A

Characteristic symptoms and / or signs occur in fasting state

Confirmation of low blood glucose by reliable assay

Resolution with administration of glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

In type 1 diabetes, hypoglycaemia is an … occurrence

There is an impaired … response

There is an impaired … of hypoglycaemia

A

Everyday

Counter regulatory hormone

Awareness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

What is gluconeogenesis?

A

The synthesis of glucose from NON carbohydrate substrates

It’s a fasting response pathway (4-6 hours after meal)

Driven by hormone glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

What is the first effect of glucagon?

A

It initiates the breakdown of the Liver glycogen to release glucose into bloodstream

Main purpose of that is to prevent hypoglycaemia

Allows neural tissues and RBCs to function normally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

How much glycogen is in the liver?

A

200g - so the secondary response is gluconeogenesis!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

What cells is glucagon secreted by?

A

Pancreatic alpha cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

What is the initial substrate for gluconeogenesis?

A

Pyruvate

Some will be formed from lactate. Lactate dehydrogenase converts lactate > pyruvate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

What are glucogenic amino acids?

A

Once amino acids have been broken down the amino group has been removed, they can then be utilised as intermediates or substrates for gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

What 2 tissues is glucose released from in gluconeogenesis?

A

The liver and kidneys

Both of these have the GLUT 2 transporter which is bi directional - can take up or release glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

Glycerol is another substrate for gluconeogenesis.
What is it produced by?

A

Hydrolysis of triglycerides in adipose tissue
Hydrolysis releases 2 products: glycerol and unesterified fatty acids (free FA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

What happens under starvation conditions?

A

Fatty acids are taken up by the liver and kidneys and they are beta oxidised to Acetyl CoA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

What is the advantage of beta oxidation?

A

Produces NADH and FADH2 - both of which can be used to make ATP in oxidative phosphorylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

What happens when there is a surplus of Acetyl CoA?

A

Converted into ketone bodies - a secondary source of energy for brain / RBC / muscle tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

What is glycolysis?

A

Glucose > pyruvate

Driven by insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

What is gluconeogenesis?

A

Pyruvate > glucose

Driven by glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

What are the 3 control points / uni directional enzymes in glycolysis?

A

Hexokinases
PFK1
Pyruvate kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

The 3 uni directional steps in glycolysis need to be … in gluconeogenesis by specific enzymes

A

Bypassed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

When can gluconeogenesis take place?

A

When there’s an energy rich environment

Utilises ATP and GTP from krebs.

Oxidative phosphorylation is the main pathway for ATP generation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

What are precursors for gluconeogenesis?

A

Pyruvate
Lactate
Oxoaloacetate
Amino acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

Animals CANNOT convert fatty acids into …
Plants, yeast and many bacteria can convert … into glucose

A

Glucose
Fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

Why are fatty acids required in gluconeogenesis?

A

Their breakdown provides the energy to drive the process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

What is anoplerisis?

A

Infusion of amino acids that is used to make new compounds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

What 3 locations does gluconeogenesis take place?

A

Mitochondria
ER
Cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

Glycolysis only takes place in the …

A

Cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

What is the co factor biotin derived from?

A

A B vitamin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

Oxaloacetate is the … in gluconeogenesis

A

1st intermediate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

Oxaloacetate CANNOT be exported from mitochondrion.
How do cells deal with this?

A

They convert oxaloacetate to Malate and then in the cytosol, convert malate back to oxaloacetate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

What is the advantage of converting oxaloacetate to malate?

A

Can transfer reducing equivalents (electrons) from inside mitochondrion to the outside
Electron donor in mitochondrion is NADH and electron acceptor in cytosol is NAD+

So can make NADH in cytosol using oxaloacetate as a starting point

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

The 2nd regulated step in gluconeogenesis is the …

A

Start point of gluconeogenesis in the cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
164
Q

How is F26BP a regulator?

A

It is an allosteric activator of PFK1 and an inhibitor of FBPase 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
165
Q

What is F26BP formed by?

A

The enzyme / bi functional protein PFK2 / FBPase 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
166
Q

What is the PFK2 / FBPASE 2 bi functional protein?

A

Has a serine in regulatory region that can be phosphorylated or de phosphorylated - either activating a kinase or phosphatase domain

Serine regulation controlled by glucagon or insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
167
Q

How is AMP an allosteric inhibitor of FBPase 1?

A

High levels of AMP indicate low energy status of the cell - need to replenish ATP levels before gluconeogenesis can continue

One way ATP levels can be replenished is by beta oxidation of fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
168
Q

What happens when there’s high levels of F26BP?

A

Insulin

Stimulates glycolysis, inhibits gluconeogenesis

PFK2 active
FBPase 2 inactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
169
Q

What happens when there’s low levels of F26BP?

A

Glucagon - ^ [cAMP]

Inhibits glycolysis, stimulates gluconeogenesis

PFK2 inactive
FBPase2 active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
170
Q

PKK 1 converts F6P into …
It is allosteric ally activated by F26BP

A

F16BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
171
Q

What happens to the produced glucose?

A

Goes back into cytosol and can get transported out of the cell using GLUT 2 transporter found in plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
172
Q

Glucose 6 phosphate CANNOT get out of the cell, why?

A

Because the GLUT transporters are specific for monosaccharides and G6P is not one!

This is the reason for phosphorylating glucose > G6P, to trap it inside the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
173
Q

How is G6P transported out of the cell?

A

The glucogenic tissues, the liver and kidneys, both have the reversible GLUT 2 transporter
It CANNOT transport G6P, only glucose

So G6P is converted to glucose to transport it out

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
174
Q

How is G6P transported into ER lumen?

A

Via a specific G6P transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
175
Q

Glucose 6 phosphate is the enzyme that … the Hexokinase step in glycolysis

It is inside the … lumen

A

Bypasses
ER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
176
Q

Where does the Cori Cycle take place?

A

In vigorously exercising muscle tissues that produce lactate.
Lactate converted to pyruvate by lactate dehydrogenase
Pyruvate converted to glucose by gluconeogenesis

Glucose then exported back to muscle tissue for utilisation
Gl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
177
Q

How does adrenaline control the cori cycle?

A

Fight or flight hormone

It induces glycolysis in muscle tissue and gluconeogenesis in liver tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
178
Q

What is the glucose alanine cycle?

A

Decreasing the formation of lactate through the conversion of pyruvate to the amino acid Alanine.

Alanine is transported to the liver where amino group is removed to become pyruvate

Pyruvate then used to make glucose in gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
179
Q

What are the 2 glucose sparing pathways?

A

Cori Cycle

Glucose Alanine Cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
180
Q

What is the purpose of the 2 glucose sparing cycles?

A

Used by skeletal muscle and liver to spare glucose for the brain and red blood cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
181
Q

The Cori Cycle: Muscle

A

ATP produced by glycolysis for rapid contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
182
Q

The Cori Cycle: Liver

A

ATP used in gluconeogenesis during recovery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
183
Q

What are normal blood glucose levels?

A

4-6 MM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
184
Q

What are the 2 amino acids that are unable to furnish carbon for net glucose synthesis?

A

Leucine and lysine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
185
Q

The first gluconeogenic steps travel through the …

A

Mitochondrion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
186
Q

What are the 4 regulated steps that bypass the 3 irreversible enzymes in glycolysis?

A
  1. Carboxylation of pyruvate > oxaloacetate OAA
  2. Decarboxylation of cytosolic OAS > PEP
  3. De phosphorylation of F16BP > F6P
  4. De phosphorylation of G6P > glucose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
187
Q

What does a reversible enzyme mean?

A

The direction of the reaction is driven by the relative amount of substrate and product

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
188
Q

What are control points?

A

They affect the rate of the WHOLE pathway but they are NOT rate limiting steps

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
189
Q

What is the Preparatory Phase of Glycolysis?

A

The phase that utilises ATP, it requires energy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
190
Q

What direction do reversible reactions go in?

A

High - low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
191
Q

How does the Payoff Phase in glycolysis generate energy?

A

ATP by substrate level phosphorylation

Reduction of NAD+ to NADH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
192
Q

How do we know that Galactose (converted to glucose) requires energy?

A

There’s an intermediate called UDP galactose which is derived from UTP - and UTP is an energy molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
193
Q

Trehalase is a plant based 2 glucose molecule.
How is it different to Maltose?

A

Difference is in the carbons bonded together to make glycosidic bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
194
Q

What are the 2 ways that Fructose can enter Glycolysis?

A

By being converted to F6P or by being converted to glyceraldehyde and dihyoxyacetone phosphate DHAP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
195
Q

What is the full conversion of glucose > CO2

A

Respiration

Aerobic conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
196
Q

What are the fates of pyruvate?

A

Alanine

VFA

Acetyl CoA (citric acid cycle)

Oxaloacetate (krebs / gluconeogenesis)

Ethanol + CO2 - the CO2 used in food production for carbonated drinks and making bread

Lactate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
197
Q

What are the 2 conditions where oxaloacetate is produced from pyruvate?

A

Under conditions of gluconeogenesis - substrate lactate > pyruvate > oxaloacetate

Under conditions of high insulin (glycolysis) - pyruvate > oxaloacetate which can be used to make citrate for TCA cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
198
Q

How do we control how much pyruvate is converted to Acetyl CoA and how much is converted to oxaloacetate?

A

A build of Acetyl CoA inhibits further formation of it from pyruvate and activates the conversion of pyruvate > oxaloacetate

So inhibition or activation controls the amounts of Acetyl coa or oxaloacetate - helps drive the cycle!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
199
Q

What is Acetyl CoA used for?

A

Intermediate in TCA cycle

Replenishes ATP stores in cell

Then used for synthesis in the cytosol - fatty acid and cholesterol synthesis (the two endpoints for Acetyl CoA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
200
Q

What conditions can Acetyl CoA build up occur?
Ie. Start inhibiting pyruvate dehydrogenase complex

A

Anaerobic conditions (low oxygen) - inhibits oxidative phosphorylation, build up of NADH and FADH2, inhibits Krebs, get build up of Acetyl CoA

Fasting conditions (more than 8 hours after last substantial meal) - lipolysis releases fatty acids, transported to liver where they are beta oxidised, an end product is Acetyl CoA.
Acetyl CoA allosteric ally activates pyruvate carboxylate - ^ oxaloacetate, which is used for gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
201
Q

Could argue that we Need … amounts of oxaloacetate and acetyl CoA to allow … to be formed and for TCA cycle to …

A

Equivalent
Citrate
Continue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
202
Q

Why is MORE Acetyl CoA made in the Citric acid / Krebs cycle than oxaloacetate?

A

Due to Anabolic compounds - they replenish intermediates in the Krebs cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
203
Q

What is the glucose sparing effect in the Cori Cycle?

A

Glucose can be exported back to muscle tissue and be reused / re utilised

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
204
Q

How much glucose does the brain need to keep it going?

A

130g in 24 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
205
Q

Why is glucose needed for vigorous exercise?

A

As glucose is metabolised much faster than fatty acids, although energy output is lower

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
206
Q

Why can’t humans sprint long distances?

A

They’ve used up all their glycogen and glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
207
Q

Can blood cells oxidise fatty acids?

A

No!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
208
Q

Cori Cycle:

Intra muscular glycogen is the … source of glucose under vigorous exercise / rapid contraction …

Glycogen broken down to glucose by hormone …

Glucose converted to … through glycolysis

Oxygen is …

Almost all pyruvate is converted to …

A

Initial
Conditions
Adrenaline
Pyruvate
Limiting
Lactate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
209
Q

What is the advantage of the glucose alanine cycle?

A

Reduces the production of lactate, decreases pH of tissues, decreases the output of that tissue that may cause damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
210
Q

Acetaldehyde is the compound that causes …

A

Hangovers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
211
Q

How is Disulfiram used to treat alcoholics?

A

It inhibits the enzyme acetaldehyde dehydrogenase > build up of acetaldehyde

So if an alcoholic is treated with this and they drink alcohol > build up of acetaldehyde > semi permanent hangover
Meant to stop them drinking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
212
Q

Humans, ethanol fermentation: we do NOT have the pyruvate carboxylase enzyme, so what happens?

A

If theres an excess of ethanol, it is converted into acetaldehyde using enzyme in liver called alcohol dehydrogenase

Acetaldehyde converted into Acetyl CoA using 2nd enzyme called acetaldehyde dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
213
Q

In healthy individuals, there’s a peak in plasma glucose concentration after each meal.
How is this mediated by Insulin?

A

Insulin is secreted from pancreatic beta cells.

Function is to remove glucose from blood > preventing glycation of blood vessels, haemoglobin and proteins in eyes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
214
Q

What are the 3 metabolic control points in Glycolysis?

A

Phosphorylation of glucose
Formation of F16BP
Formation of pyruvate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
215
Q

What are the roles of ATP?

A

Donate an inorganic phosphate

Provide energy to drive reactions from left to right - energy is provided by hydrolysis of phosphodiester bond in ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
216
Q

What are Isoenzymes?

A

Enzymes with an identical function that are produced from different gene products

Have different tissue expression snd different kinetic properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
217
Q

Hexokinase 1

A

Most tissues (ubiquitous)

Broad specificity - in terms of 6 carbon monosaccharides

Low Km - high affinity for monosaccharides

Product inhibition - glucose 6 phosphate is an inhibitor of enzyme

Hyperbolic kinetics - Michaelis Menten

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
218
Q

Hexokinase 4 (glucokinase)

A

Liver, pancreas

Biosensor in Beta cells

Broad specificity

High km, low affinity

High Vmax

Sigmoidal kinetics - cooperativity - different active sites work together

Allosteric control - glucose and F6P

REGULATION by Insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
219
Q

How does glucokinase act as biosensor?

A

Acts as a glucose sensor for high blood glucose concentrations - > 6 MM which would = Hyperglycemia

Glucokinase phosphorylates the glucose taken up to cause the secretion of insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
220
Q

The liver is the 1st tissue that dietary sugars will reach. What are those blood sugars used for?

A

Replenish ATP levels

Replenish glycogen

Convert into FA and cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
221
Q

What is the purpose of glucokinase in reacting to hyperglycemia?

A

Decreases the high glucose concentration by insulin secretion and metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
222
Q

At what glucose concentration is Hexokinase 1 fully saturated due to its low km?

A

5MM - means it is always saturated under feeding or fasting conditions! It is working at full capacity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
223
Q

Hexokinase 1 is fully saturated at normal glycemic concentrations and above but has a relatively low vmax.
What does this mean?

A

It is active all the time but only takes up a small amount of glucose at 1 time.

Takes up enough for brain to function but doesn’t take up excess!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
224
Q

How is glucokinase regulated by Glucose Kinase Regulatory Protein GKRP?

A

It transports Hexokinase 4 from cytosol into nucleus where it is INACTIVE > glycolysis is inhibited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
225
Q

How does the regulation of glucokinase by by F6P and glucose affect glycolysis?

A

F6P - allosteric inhibitor of glycolysis in terms of this enzyme

Glucose - allosteric activator of glycolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
226
Q

What are the group of isoenzymes that catalyse glycolysis control point 2?

A

Phosphofructokinases - PFK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
227
Q

Why is glycolysis control point 2 an important control step?

A

The product F16BP is the 1st dedicated product in glycolysis, means that G6P can be converted into other pathways (glycogen synthesis, pentode phosphate pathway)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
228
Q

What is PFK1 regulated by?

A

Substrate concentration of ATP, F6P

Energy levels of ATP, citrate, ADP, AMP

F26BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
229
Q

PFK 1 has 4 different subunits, each with a catalytic site and an allosteric site.
What is the function of the catalytic sites?

A

Converts F6P into F16BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
230
Q

What isoenzyme is F26BP made by?

A

PFK 2 - it preferentially converts F6P into F26BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
231
Q

F26BP is hydrolysed back to F6P by…

A

FBPase 2 - fructobisphosphatase

232
Q

What does High ADP (low ATP) do to the activity of PFK 1?

A

It competitively displaces ATP from allosteric site.
When ADP binds to site, it causes a conformational change that increases the activity of PFK 1

233
Q

F26BP is not used for any other purpose other than regulating the 2 enzymes…

A

PFK 1 and FBPase 1

234
Q

Why do cells make F26BP, as it has no direct metabolic advantage?

A

Insulin > PFK2 > increased F26BP > PFK1 > increased glycolysis

235
Q

What is anaerobic glycolysis and why is it beneficial?

A

Using up NADH to make NAD+ again

Beneficial as it allows glycolysis to continue, can continue making ATP

236
Q

Step 10 in glycolysis

A

Uni directional

Bypassed in red blood cells

Net outcome is 2NADH and 2 ATP under aerobic conditions

237
Q

What are the allosteric inhibitors of pyruvate kinase?

A

Alanine - skeletal muscle, liver

High levels of ATP - don’t need glycolysis to take place

High levels of Acetyl CoA - fasting response - inhibits glycolysis

Long chain fatty acids

238
Q

What is an allosteric activator of pyruvate kinase?

A

F16BP - an example of Feed forward control as it is made 6 steps prior to conversion to PEP

239
Q

What is pyruvate kinase deficiency?
(Haemolytic anaemia)

A

Form of anaemia due to abnormal breakdown of red blood cells

PK deficiency is the 2nd most common cause of enzymatic related haemolytic anaemia

240
Q

PK deficiency characteristics

A

Affects allosteric control and protein levels

Abnormal Km or vmax

Abnormal response to F16BP

ALTERED enzyme activity, stability or concentration

241
Q

What is PK deficiency caused by?

A

Mutations at the gene levels - ie the DNA sequence

242
Q

What is the Warburg effect?

A

Where glycolysis takes place under anaerobic conditions. Found in some tumour cells

243
Q

What happens in tumours under the Warburg effect?

A

Do NOT have pyruvate going into mitochondria due to lack of oxygen

Pyruvate is converted into lactate

Uses up NADH produced in glycolysis and oxidises it back to NAD+

244
Q

What is the benefit of Warburg effect to the tumour cells?

A

They can use glucose as an energy source due to the substrate NAD+ which can be re utilised

= glycolysis occurs at elevated rate

245
Q

What is the downside of the warburg effect in tumour cells?

A

Produce a lot less ATP per unit glucose

246
Q

The Warburg effect - the inhibition of glycolysis has been used to treat tumours.
Examples?

A

Transcription factor HIF1 - hypoxia inducible factor

It regulates gene transcription under low oxygen conditions (hypoxia)

247
Q

18F FDG is used in clinical conditions to detect …
It contains 18F stable … and can use instruments to detect higher levels called …

A

Tumours
Isotope
PET scanners - positron emission tomography

248
Q

What are PET scanners and how do they work?

A

An analogue of glucose. Cells take it up thinking it’s glucose > converts it to G6P analogue > gets trapped in cells

Glycolysis takes place at faster rate in tumours so there’s increased uptake of that compound > detected via PET scanner > red = high levels > eg in Brain

249
Q

What is the irreversible oxidative phase of pentose phosphate pathway?

A

Contains the controlling enzyme for PPP - there is only 1 control point!

250
Q

What is the reversible NON oxidative phase in pentose phosphate pathway?

A

Where unusual sugars are inter converted

Controlled by insulin at level of transcription

Utilises G6P as the starting substrate

251
Q

What are the 3 endpoints that glucose can enter a cell?

A

Pyruvate through glycolysis

Glycogen storage (liver)

Pentose phosphate pathway - synthesis / protection

252
Q

Pentose phosphate pathway

A

NOT for energy production - NO ATP or NADH produced

Occurs in cytosol

253
Q

What specialised metabolic needs does pentose phosphate pathway cater for?

A

NADPH

Ribose 5 phosphate

Dietary pentose sugar metabolism

Synthesis of aromatic amino acids

254
Q

What happens in the oxidative phase of the PPP?

A

G6P is oxidised and 2NADP+ is reduced to 2NADPH

Catalysed by G6P dehydrogenase - the control point in ppp!

255
Q

Where does the PPP cycle take place?

A

Liver and adipose (fat) tissue

256
Q

What is the role of glucose 6 phosphate dehydrogenase in the PPP?

A

Primary point of regulation - it is the CONTROL POINT in ppp

Converts NADPH to NADP+

NADPH: NADP+ ratio is 100:1 in the cell - high ratio!

Insulin

257
Q

How is G6P dehydrogenase regulated in ppp?

A

By amount of NADPH that is formed relative to NADP+ in the cell. NADPH is product inhibitor of G6P D enzyme = high ratio in the cell

Insulin - it regulates amount of G6P D enzyme at the level of transcription

258
Q

What is the metabolic effect of the NADPH : NADP+ 100:1 ratio?

A

It will only activate G6P D enzyme when NADPH levels are low!

Normal conditions, will inhibit the enzyme and so PPP. This is so that energy is generated first so synthesis can proceed!

259
Q

What is the reason for the difference in structure between NADPH and NADH?
(NADPH has extra phosphate group)

A

Means NADH is utilised by specific enzymes - eg in oxidative phosphorylation

The phosphate group makes a difference in terms of binding to enzymes as there is stereo specific binding of ligand to enzyme active sites!

260
Q

What is the non oxidative phase in ppp?

A

The regeneration of G6P from R6P that occurs in the liver and adipose tissue

261
Q

Why does non oxidative phase of ppp take place in liver and adipose tissue?

A

Liver utilises NADPH for lipogenesis - fatty acid and cholesterol synthesis

Adipose tissue utilises NADPH to synthesise FA which are converted to triglycerides = biggest storage form of energy from the diet!

262
Q

What is ribose 5 phosphate used for?

A

Synthesis of nucleic acids / nucleotides

Specifically DNA / RNA as they are only made when cells divide - which requires high energy status

263
Q

What is erythrose 4 phosphate used for?

(Ppp)

A

To make the aromatic amino acids - eg phenylalanine, tyrosine, tryptophan

(Benzene ring like structures)

264
Q

What happens in FA synthesis and what do you need?

A

Add 2 carbons for every cycle taking place

Need 2 NADPH to provide e-

Acetyl CoA as a starting point

265
Q

What are the roles of NADPH?

A

Reductive biosynthesis (fatty acids)

Reduction of hydrogen peroxide (GSH / GSSG)

Cytochromes p450

Phagocytosis

Synthesis of nitric oxide

266
Q

What are the 2 pathways where NADPH donating e- is important?

A

Fatty acid synthesis

Cholesterol synthesis

267
Q

What is the role of NADPH in reductive biosynthesis?

A

Supplies reducing equivalents (donates electrons)

268
Q

Reduction of hydrogen peroxide: why can oxygen be a poison?

A

It can be reduced (addition of e-) to highly reactive intermediates - superoxide, hydrogen peroxide, hydroxyl radicals

269
Q

Humans have protective mechanisms to reduce the effect of oxygen radicals but they decline with age.
What is the effect of the radicals?

A

Can modify proteins, lipids, nucleic acids

Modified FA can change functionality of membranes

Oxidised FA and cholesterol can cause Atherosclerosis - formation of atherosclerotic plaques - blockage of blood vessels that cause heart attacks!

270
Q

What are the 2 diseases that can be directly affected by oxygen free radicals?

A

Cancer and ageing

271
Q

What is oxidative stress?

A

When there is increased levels of free radicals

Causes cancer and ageing

272
Q

What are the 2 protective me chains for oxidative stress?

A
  1. Enzyme systems - superoxide dismutase SOD, catalase, glutathione peroxidase
  2. Anti oxidant chemicals- Ascorbate, vitamin E, b carotene

Vitamin C (ascorbate) is water soluble and vitamin E is hydrophobic
B carotene is converted into vitamin A

273
Q

What does catalase do?

A

Breaks down H202 to oxygen and hydrogen

(Metals as cofactors)

274
Q

What does superoxide dismutase do?

A

Breaks down superoxide intermediate into oxygen and hydrogen peroxide

275
Q

What is glutathione (GSH) peroxidase and what does it do?

A

A tri peptide made up of 3 AA

Breaks down H202 to water. In the process it oxidises GSH (reduced glutathione) into the oxidised version GSSG

276
Q

Biologically active form:

GSH - reduced glutathione

A

It has 3 AA: gammaglutamyl, cysts yk and glycine.

IMPORTANT: it has a cysteine which has a reduced sulfhydryl group SH.

2 reduced GSH form 1 oxidised GSSG

277
Q

Biologically intert form:

GSSG - oxidised glutathione

A

Oxidised glutathione is characterised by a disulphide bridge.

The ratio of GSSG : GSH is an indicator of oxidative stress, the higher the ratio, the stronger the OS in the cell!

278
Q

How do we recycle GSSG back to GSH?

A

GSH reductase can reduce the disulphide bond in the GSSG to form 2 molecules of GSH

GSH reductase requires NADPH as the cofactors that donates e-.

Main source of that NADPH is the ppp!

279
Q

What is the main reason we need Selenium in the diet?

A

To decrease the levels of oxygen free radicals using the glutathione (GSH) peroxidase enzyme

280
Q

What is the Microsomal System?

A

Microsomes are purified ER

Small vesicles that contain cytochrome p450 enzymes

Used in drug metabolism (Xenobiotics)

281
Q

What are the 2 functions of cytochrome p450 in drug metabolism?

A

Convert hydrophobic drugs into hydrophilic products - to increase excretion of these compounds

To specifically convert pro drugs into ACTIVE drugs - ie cancer drugs

282
Q

What are the 3 examples of the Mitochondrial System?

(That use cholesterol as the substrate)

A

Steroids - hormones eg oestrogen, testosterone

Bile acids - amphipathic, have a hydrophilic and hydrophobic component.

Vitamin D - made in liver, skin and kidney

283
Q

What are the 2 roles of bile salts in the body?

A

Small intestine - act as biological detergents, help to solubilise dietary fats. This allows lipases to break down fats for them to be absorbed

Main mechanism for getting rid of excess cholesterol - converted into bile salts which is excreted in small intestine through faeces

284
Q

What is the misconception regarding vitamin D?

A

The body started shutting down vitamin D synthesis after half an hour! So no point sitting in the sun all day

285
Q

What are the cytochrome p450 enzymes?

A

Group of enzymes that have a colour - they absorb light in the visible range

All of them have a metal cofactors that provides the colour. Depends on the metal

Eg if cytochrome p450 has iron in it, then it is normally a red colour

286
Q

What does the p450 part of cytochrome p450 mean?

A

Means that in the presence of carbon monoxide, this group of enzymes shows an absorbance peak at 450nm

CO binds tightly to Fe containing proteins eg haemoglobin

287
Q

What 2 cofactors does cytochrome p450 utilise?

A

Oxygen

NADPH - donates electrons

288
Q

Why is ROH much more reactive than RH?

A

Contains the nucleophile O2

289
Q

What is phagocytosis?

A

Breakdown of foreign compounds by macrophages, phagocytes etc

Cell engulfs particle, digests it and expels the waste products

290
Q

What is the process of phagocytosis?

(Oxygen independent system)

A
  1. Lysosome mediated process - intracellular recycling plants, they fuse with vesicle. Have an acidic ph
  2. Acidic ph - around 4.5. Specific enzymes. Acidic environment helps breakdown foreign compounds.
  3. Proteolytic enzymes - break down proteins. + lipases and nucleases
291
Q

Process of phagocytosis/ oxygen dependant system

A
  1. Oxygen dependant degradation depends on NADPH and production of reactive oxygen species
  2. NADPH dependant oxidase generated hydrogen peroxide H202
  3. Myeloperoxidase then generates hypochlorite OCL-. This is the active component of bleach
292
Q

The oxygen dependant process of phagocytosis actively forms oxygen free … in terms of …

A

Radicals
Protection

293
Q

Why is nitric oxide required and why does it need to be made continuously?

A

Required for proper functioning of blood vessels

Has a very short half life of around 3-10 seconds

294
Q

What does nitric oxide synthase do?

Why does it need arginine and NADPH?

A

Converts oxygen to nitric oxide

Arginine - donates the nitrogen
NADPH - provides the e-

295
Q

What are the functions of nitric oxide?

A

Vasodilator - blood vessel dilation

Protection against ischaemic damage

Cardiovascular signalling molecule

Neurotransmitter

Prevents platelet aggregation - linked to Atherosclerosis

Bactericidal - NO combine with a further oxygen to form anti bacterial compounds

296
Q

What is Wernicke Korsakoff Syndrome?

A

Memory disorder due to vitamin B1 (thiamine) deficiency (beriberi) - decreases uptake to lower than 10% of normal in the intestine

Associated with alcoholism, malnutrition and thiamine transporter variants

Damaged nerve cells

Transletolase is a thiamine / vitamin B1 dependant enzyme in the PPP - requires it for full activity!

297
Q

What are inborn errors of metabolism due to?

A

Genetic modifications

298
Q

Why is transketolase important?

(Wernicke korsakoff syndrome and PPP)

A

Need the enzyme to convert R5P back to G6P in the liver. This increases production of NADPH

If we have a deficiency of thiamine cofactor, enzyme cannot function properly and NADPH production decreases.

Effects nerve and neuro function

299
Q

Glucose 6 phosphate dehydrogenase deficiency:

A

Common - more than 209 million affected

> 300 different mutations (polymorphisms)

Characterised by haemolytic anaemia - RBCs break down faster than normal

Small effect on life expectancy

But gives resistance to malaria!

300
Q

What are polymorphisms?

A

Mutations at the gene level

Can be silent (nothing happens), conservative (small effect), NON conservative (large effect, or truncation (stop codons etc)

301
Q

What is the main effect of G6PD deficiency?

A

At the level of erythrocytes, RBCs

Leads to a lowered recycling of GSSG back to GSH - means individuals are susceptible to OS

302
Q

What are the 2 endpoints of G6PD deficiency in the RBCs?

A

Haemoglobin is denatured - as it contains reduced sulphydryls, can be detected in RBCs in the form of Heintz Bodies

Oxidation of phospholipids - leads to haemolysis - breakdown of RBCs, releasing haemoglobin

303
Q

Why is G6P D deficiency common in RBCs?

A

In normal cells, there is the GSH peroxidase system that protects against O2 free radicals.

People with the deficiency in G6P can only use the enzyme in PPP to convert NADP+ back to NADPH.
If that level is decreased, the response is decreased.

All other cells EXCEPT for erythrocytes have a backup enzyme system called NADP+ dependant malate dehydrogenase system

304
Q

What is the main function of the NADP+ dependant malate dehydrogenase system?
Why do RBCs not have this system?

A

To transport pyruvate across the mitochondrial membrane

RBCs do NOT have mitochondria so do NOT have this system

305
Q

Most individuals with G6PD deficiency are …
There is no effect unless they are triggers called …
They convert someone from asymptomatic to …

A

Asymptomatic
Precipitating factors
Symptomatic

306
Q

What are the precipitating factors in G6PD deficiency?

A

Oxidant drugs - antibiotics, antimalarials, antipyretics. They all increase oxidative potential in a cell. They can trigger haemolysis

Favism - fava bean. Induces haemolysis

Infection - phagocytosis produces H202 and hypochlorite. Both have high oxidative potential

307
Q

G6PD deficiency causes neonatal jaundice.
What is this?

A

In babies liver has NOT fully developed, they struggle to breakdown haem, leads to increased levels of Bilirubin

Causes neonatal jaundice, yellow colour due to high levels of haem

Treatment is UV light - hydrolysis bilirubin and allows for excretion

308
Q

What does the phosphorylation of tyrosine residues within the kinase domain do?

A

Enhances kinase activity

309
Q

What does phosphorylation of tyrosine residues OUTSIDE of the domain do?

A

Generates high affinity docking sites for intracellular signalling molecules

310
Q

What is RAS GEF needed for?
And what is GEF?

A

Needed for GTP or GDP exchange

GEF = guanosine nucleotide exchange factor - GEF can activate RAS which is important for lots of activity

311
Q

What do activated signalling proteins do?

A

Relay signal downstream

312
Q

Ras family of monomeric GTPases function as a …

A

Molecular switch

313
Q

What do Ras GTPase activating proteins do?

A

Increase the rate of GDP hydrolysis by Ras itself (which will inactivate RAS)

314
Q

Why can active RAS induce the phosphorylation cascade?

A

As ras is a kinase

315
Q

RTKs can activate…

A

Ras

316
Q

Ras activates a cascade of mitogen activated kinases which includes:

A

RAF - MAP kinase kinase kinase (MAPKKK)

Mek - MAP kinase kinase (MAPKK)

Erk - MAP kinase (MAPK)

317
Q

What does a MAP kinase do?

A

Something that induces growth

318
Q

What happens as a result of tyrosine kinase receptor activation?

A

Transcriptional effects - changes in gene expression etc

Changes in protein activity - could change properties of cell

319
Q

Why so downstream signals activated by RTKs and GPCRs overlap?

A

So they can end up in target proteins that are turned on

Or can induce transcriptional changes / regulation

320
Q

Why do cells normally have a combination of G protein coupled receptors GPCRs and receptor tyrosine kinases RTKs?

A

So that Ligands binding to receptors can converge

321
Q

What are the 4 basic mechanisms for cellular communication?

A

Contact dependant (direct contact)

Paracrine signalling

Synaptic signalling

Endocrine signalling

322
Q

What is contact dependant signalling?

A

Where 1 cell has a protein, glycoprotein or glycolipid on surface that is going to act as a ligand for receptor on cell next to it!

Need to be physically next to eachother to send that signal

323
Q

What is paracrine signalling?

A

Send messages to cells immediately near them - short lived signals

324
Q

What is synaptic signalling?

A

From nerve to target cell

Neurotransmitters in axon, are already packaged in synaptic cleft, ready to be released
When released > very small diffusion distance, can respond quickly!

325
Q

What is endocrine signalling?

A

Signals designed to travel furthest, go in blood to other sites in body

Act wherever the target cell has got a corresponding receptor

326
Q

Why is cell communication / signalling so important?

A

Regulates cell behaviour - depends on multiple extracellular signal molecules

Allows cells to: survive, grow and divide (proliferate) and differentiate (more specialised cells eg monocytes

327
Q

What would happen to a cell if there was NO stimulus / cell communication?

A

Cell would die!

Apoptotic cell

328
Q

What is KEY about contact dependant signalling?

A

Cell can’t exist / survive unless they have contact dependant communication from cells around them

329
Q

What type of cells don’t need contact dependant signalling?

A

Blood cells - leukocytes, erythrocytes

As they are in suspension

330
Q

What are examples of paracrine signalling?

A

Fibroblast growth factor FGF - proliferation and differentiation

Transforming growth factor beta TGFB

Wnt signalling - embryo development

Chemotaxis

331
Q

What is chemotaxis?

(Paracrine signalling)

A

Motility in the direction of a localised mediator

Bacterial toxins - formyl peptides

Chemokines - ILB

332
Q

Why do phagocytes follow around bacteria and engulf it?

A

Because chemokines are being released

The higher the concentration of them, the easier it is for leukocyte or phagocyte to follow it

333
Q

What are the steps of Cholinergic transmission?

A
  1. Synthesis of acetylcholine
  2. Uptake into storage vesicles
  3. Release of neurotransmitter
  4. Binding to receptor
  5. Degradation of acetylcholine
  6. Recycling of choline
334
Q

Why is endocrine signalling different to the others?

A

Longer lasting signals because they need to travel far or need to be constantly in contact with cell next to them

Taken everywhere by the blood

ONLY works if you have receptor and the signal

335
Q

Extracellular signals can act slowly or rapidly. Examples of these?

A

Slowly - growth, cell division, transcription

Rapidly - cell movement

336
Q

Different cell types respond differently to the … extracellular signal molecule

Eg acetylcholine

A

Same

337
Q

How is calcium signalling detected?

A

Fura 2 am

An aminopolycarboxylic acid which binds to free calcium

It is a ratiometric fluorescent dye - changes intensity of signal with calcium concentration

It is excited at 340nm and 380nm light

Ratio of emissions at those wavelengths is directly related to the amount of intracellular calcium
Ie. If there’s a high concentration of calcium = high signal intensity and vice versa

338
Q

What are the common disaccharides that are linked by glycosidic bonds?

(Composed of 2 monosaccharides)

A

Sucrose - glucose and fructose

Lactose - galactose and glucose

Maltose - glucose and glucose

339
Q

Why do dietary carbohydrates have to be broken into monosaccharides in humans?

A

We have transporters specific to monosaccharides.
So have to be broken down to facilitate entry into the small intestine

340
Q

What is sucrose intolerance due to?

A

Sucrase enzyme deficiency

High in Icelandic population

341
Q

What is lactose intolerance due to?

A

Lactase enzyme deficiency - most common!

342
Q

What is sorbitol intolerance due to?

A

Sorbitol dehydrogenase enzyme deficiency - converts sorbitol into fructose which can then enter glycolysis

Sorbitol found in pears, avocados and is used as a low calorie sweetener

Sorbitol is metabolised very slowly by most humans

343
Q

What are homopolysaccharides and what are some examples?

A

Consist of 1 type of monosaccharide

Best examples are glycogen, Starch - both homopolysaccharides consisting of glucose

344
Q

What are heteropolysaccharides and some examples?

A

Contain different types of sugars / quite often linked to proteins (glycoproteins) and the glycoproteins are important in viral infections etc

345
Q

What is glycogen?

A

Major storage form of glucose in humans and other animals

346
Q

How much glycogen can the liver store?

A

200g

347
Q

What enzymes are required to break the bonds in glycogen?

A

A1-4 : glycogen phosphorylase

A1-6 : debranching enzyme

348
Q

What 2 organs store glycogen?

A

Liver - to provide glucose in fasting phase 6-8hrs after last meal. To prevent hypoglycaemia

Skeletal muscle - can store up to 300g glycogen depending on exercise level

349
Q

What is the difference between skeletal muscle and liver glycogen?

A

In skeletal muscle, glycogen has to be utilised during exercise to make ATP

Skeletal muscle DOES NOT have glucose transporter to transport glucose out!

350
Q

Glycogen

A

Branched homopolysaccharide of glucose

Glucose monomers form a1-4 linked chains

Branch points with a1-6 linkers every 8-12 residues

Molecular weight reaches several millions

MAIN storage polysaccharide in a animals

351
Q

Starch

A

A mixture of 2 homopolysaccharides of glucose:

Amylose - unbranded, a1-4
Amylopectin - branched, a1-6 every 24-30 residues

Starch is the main storage polysaccharide in plants

352
Q

Cellulose

A

Most common polysaccharide in the world!

B1-4 glucose units

Hydrogen bonding between chains

Water insoluble

Cellulases: bacteria in ruminants and termites

353
Q

Why can humans NOT digest cellulose?

A
  1. Cellulose contains B1-4 bonds and we do not have the enzymes (cellulases) required to break them down
  2. Hydrogen bonding means cellulose is water insoluble and we need things to be water soluble to digest them
354
Q

How is energy generated when two pyruvates are produced per glucose?

A

By reducing NAD+ to NADH

By phosphorylation of ADP to ATP

355
Q

What is the net yield of NADH and ATP from 1 glucose?

A

2NADH

2ATP

356
Q

When does anaerobic metabolism take place?

A

Takes place in conditions of oxygen deficiency

357
Q

Why do we get the conversion of glucose > pyruvate > lactate?

A

Due to inhibition of oxidative phosphorylation due to LACK of oxygen

This inhibits krebs > inhibits conversion of pyruvate to Acetyl CoA

358
Q

Under what conditions does lactate production take place?

A

Oxygen depletion - eg when you train

Hypoxia - lactate used as a bio marker for how much hypoxia there is

Red blood cells - don’t have mitochondria

Warburg effect - cancer cells / tumours use anaerobic metabolism as they have low level of oxygen transport

359
Q

Cows have bacteria in their forgut that secrete cellulases
What do these do and how are they metabolised?

A

Cellulases break down cellulose to glucose

Glucose 1st metabolised by the bacteria to pyruvate.
In the anaerobic environment of the forgut, pyruvate is converted into volatile fatty acids!

360
Q

Cows DONT take up glucose, they take up…

A

Volatile fatty acids

361
Q

What are the volatile fatty acids?

A

Acetate - 2C

Propionate - 3C

Butyrate - 4C

362
Q

How is acetate utilised by the cow?

A

Feeds into Krebs cycle as a 2 carbon donor - forms Acetyl CoA

363
Q

How is butyrate utilised by the cow?

A

Forms a B- hydroxybutyrate which is a ketone body and can be broken down into Acetyl CoA

Used as an energy source

364
Q

How is propionate utilised by the cow?

A

Converted into lactate in the liver

Lactate > pyruvate and pyruvate > glucose via gluconeogeneis

365
Q

When cows eat grass, the bacteria produce the glucose but the cows DO NOT take up the glucose, they take up … to then make the glucose!

Cows get the glucose from…

Disadvantage?

A

Volatile fatty acids

Gluconeogenesis

366
Q

What is a Uniport glucose transporter?

A

Transports 1 compound across the membrane and is driven by diffusion - high to low concentration

367
Q

What is a Symport cotransporter?

A

Transports 2 compounds across membrane

368
Q

What is an Antiport cotransporter?

A

Transports 1 compound into the cell and another out of the cell!

369
Q

Uniport transporter amino acid is in the membrane. What are its 2 confirmations?

Eg GLUT1 - erythrocytes

A

T1 - confirmation that opens to outside and will bind glucose

T2 - conformation that opens to other side of membrane

370
Q

How do the Uniport Energy Independent Transporters work?

A

Binding glucose causes a conformational change that converts T1 into T2.
T1 had a high affinity for glucose

T2 has a low affinity for glucose so releases it into the cell! This changes conformation back to T1, opening up outside of cell and allowing another glucose to bind

371
Q

GLUT = glucose transporter

What type of transporters are GLUT 1,3,4 and 5?

A

High affinity glucose transporters, so bind glucose at very low concentrations

So can transport glucose even under fasting conditions!

Are uni - directional: only transport glucose in 1 direction

372
Q

The different GLUT transporters

A

GLUT1: erythrocytes and brain
GLUT2: liver, kidney, intestine, pancreatic B cells (bi directional)
GLUT3: neurons
GLUT4: adipose tissue, skeletal muscle (the ONLY one regulated by insulin and glycogen)
GLUT5: small intestine, testes, muscle
GLUT6: gluconeogenic tissues

373
Q

What is special about GLUT5?

A

Specific / has a high affinity for fructose, found in small intestine

Fructose intolerance linked to low expression of GLUT5 in small intestine

374
Q

What is special about GLUT7?

A

Only expressed in ER!

Specifically required during gluconeogenesis

375
Q

What is special about GLUT 1,3 and 4?

A

Glucose uptake form blood (high affinity)

376
Q

What is special about GLUT2?

A

Bi directional (low affinity)

377
Q

GLUT 4 in fasting conditions is stored in vesicles inside the cell.
Insulin is secreted in healthy individuals when blood glucose concentrations are ABOVE 6MM.
What does binding of insulin trigger?

A

Triggers a set of enzymes (signalling cascade) to initiate phosphorylation or de phosphorylation actions

This leads to transfer of GLUT4 vesicles to plasma membrane

Vesicles fuse with membrane and GLUT4 transporters are expressed on membrane = biologically active!

When glucose concentrations are reduced, there’s a reduction of Insulin and inactivation of this cascade

378
Q

What are some potential negative effects of glucose in the blood?

A

Glycation of proteins - means theres a NON enzymatic modification of proteins in the blood
Eg glycated haemoglobin transports LESS oxygen and is used as a bio marker
For long term high blood glucose

Proteins in the eyes can get glycated - can lead to blindness!

379
Q

How is adipose tissue important for metabolism?

A

Adipose tissue is there to store energy

Glucose is transported into the tissue where it is stored in the form of triglycerides!

380
Q

Sodium dependant monosaccharide co transport system

A

Transports glucose AGAINST concentration gradient

Energy requiring process: Chemical + electrical potential / Na+K+ ATPase

Co transport of Na+

Epithelial cells of intestine, renal tubules

381
Q

What is the Kt / Kd?

A

The dissociation constant

The lower the kt, the higher the affinity for that ligand!!

382
Q

What does the initial velocity of glucose mean?

A

The rate at which glucose is transported into the cell!

383
Q

What is a function of epithelial cells?

A

To transport dietary carbohydrates into the blood

384
Q

How does glucose get from intestinal lumen into epithelial cells?

A

Using a Symport protein - a sodium DEPENDANT co transporter

The sodium provides the energy to transport glucose against CG

Can do this because concen of sodium outside cell in intestinal lumen is HIGHER than inside
And sodium is + charged whereas inside of the cell is - charged

385
Q

How does glucose get out of the cell into the blood?

A

Using a GLUT 2 transporter as it is bi directional

It is expressed on the basal surface

It transports glucose out of the cell when there’s HIGH concentrations inside

386
Q

Intestinal lumen:
Na+ glucose Symporter on apical surface is driven by…

A

High extracellular na+ concentration

387
Q

Blood:
Glucose uniporter GLUT2 on basal surface facilitates…

A

Downhill efflux of glucose

388
Q

What does the sodium potassium ATPase Antiport protein do?
Inside and outside of the cell?

A

It transports Na+ out of the cell to help maintain low sodium concentration

Inside cell: maintains - charge inside cell and can drive glucose uptake through Na+ glucose symporter

K+ is also driven into the cell at the same time!

389
Q

What does guanylyl Cyclase do?

A

Converts GTP into cyclic GMP - cGMP

390
Q

How is guanylyl Cyclase different to adenyl Cyclase?

A

Receptor associated (not membrane associated)

Soluble - can be activated by things like nitric oxide

391
Q

What do all the mechanisms of decreases signalling do?

A

They ALL decrease the output from the signalling pathway!

392
Q

What is receptor sequestration?

A

Receptor associated with signal and get internalised in an Endosome

Ph drops + ligand is released from receptor - ligand then degraded by proteins in endosome

Receptor will get recycled back out to membrane

^ in endocytosis will decrease amount of receptors on cell surface

393
Q

What is receptor down regulation?

A

Further drop in ph and endosome becomes LATE endosome + then lysosome by fusion!

Degrades ALL components and receptor NOT allowed back onto cell surface

Permanently reduces no of receptors on cell surface. Less receptors = less response

394
Q

What is receptor in activation?

A

While receptor bound to ligand, it causes some intra cellular processes that cause inhibition

May modify receptor - stops it receiving signals

Or methylation or acetylation may cover phosphorylation site = stops proteins associating with receptor when activists

= self limiting!

395
Q

What is inactivating of signalling protein?

A

Inhibition may inactivate the down stream enzyme = inactivation of signalling proteins

396
Q

What is production of inhibitory protein?

A

When there’s activation of enzymes with enzyme associated receptors, we get an inhibitory process

A protein can inhibit activation of receptor

Does this through physical binding

397
Q

What are the mechanisms of decreased signalling?

A

Receptor sequestration
Receptor down regulation
Receptor inactivation
Inactivation of signalling protein
Production of inhibitory protein

398
Q

What is the role of B arrestin in GPCR desensitisation?

A

B arrestin binds to phosphorylated GPCR Which prevents the re association of the trimeric G protein (GRK) with receptor = preventing further signals!

Only works if there are multiple phosphorylation sites (hyper phosphorylation)

399
Q

B arrestin prevents further signalling in GPCR.
So can’t activate downstream things like:

A

Adenyl Cyclase
Can’t generate IP3
Can’t release calcium
Can’t produce diasolglycerol

400
Q

What can scaffolding proteins do?

A

Control the signalling cascade

401
Q

Scaffold protein 1 has a very specific binding / docking site for kinase A,B and C
Why is it essential?

A

Only lets them sit in that order!

They have to bind in that order to receive the signal = specific response

402
Q

What does docking / scaffolding ensure?

A

Ensures that everything is kept close together in the membrane for rapid transmission of the signal!

403
Q

Sev RTK activates Ras in the fly eye
What is the equivalent of the adapter protein Drk in humans?

A

Grb2 and Ras GEF (also called seven less SOS)

404
Q

How does the Sev RTK in fly eye bind? How is it similar to humans?

A

The adaptor protein (Drk) binds through SH3 and SH2 domains to the Ras GEF (SOS) - same as humans!

As it is a guanine exchange factor it swaps out GDP and inactive Ras binds instead to GTP!

Can only do that in the presence of GEF. Now it is active > shape change > downstream signalling

405
Q

What is the difference between Drk in fly eye and humans?

A

IGF1 is binding to soluble peptides that are travelling around the body

Here, we’ve got Contact Dependent Signalling as a result of engagement of 2 membrane bound components

406
Q

What do the interaction domains - Src homology - do?

A

Src homology domains bind to phosphotyrosine residues in tyrosine kinases - acting as a scaffold to recruit further signalling components

407
Q

Proteins have lots of domains - what are they?

A

Patterns of amino acids that make a particular shape and allow something to bind to it

Complementary to a particular protein

408
Q

Jack of all trades has … interaction domains

A

Many

409
Q

What is an interaction domain?

A

Means there is a platform for a protein to interact with another protein

410
Q

Ras family GTPases activate a MAP kinase signalling molecule:

A

MAP kinase kinase kinase - Raf is important in cell proliferation and induces a phosphorylation cascade

1 molecule of Ras may be enough to phosphorylate thousands of the MAP kinase kinase - Mek!

The cascade exponentially ^ the number of the final output Map kinase - Erk, which can cause 2 effects

411
Q

What are the 2 effects that MAP kinase - Erk can induce?

A

Changes in protein activity - eg protein kinase A can phosphorylate something in the nucleus
Takes seconds or minutes

Changes in gene expression - takes hours or days = SLOW

412
Q

What does the PI 3 / PKB (Akt) signalling pathway stimulate?
What is Akt activated by?

A

Animal cells to survive and grow

By mTOR in complex 2 with rictor

413
Q

What happens if we get dissociation of Akt from its complex?

A

It can associate with mTOR in a separate complex - complex 1. This can induce cell growth

If it stays there - it is able to phosphorylate Bad - a protein that sits in mitochondrial membrane

414
Q

What happens to the Bad protein if Akt is present?

A

Akt will act as a kinase and phosphorylate Bad. This inactivates it and it binds to a 14 3 3 protein = signal for degradation! (Ubiquitin ligase signal)

Also get release of an active form = induces inhibition of apoptosis = sign for cell survival!

(When Akt is NOT present, Bad is associated with its inhibitory complex)

415
Q

What is mTOR and what protein complex is it in?

A

mTOR = mammalian target of rapamycin

Either in protein complex 1 or 2, NOT both!

416
Q

What does mTOR in complex 2 contain?

A

Rictor protein

Insensitive to rapamycin, activates Akt / PKB

417
Q

What does mTOR in complex 1 contain?

A

Riptor protein

Sensitive to rapamycin

Promotes ribosome production and protein synthesis and inhibits protein degradation

Complex 1 stimulates cell growth and survival through nutrient uptake and metabolism

418
Q

What happens when mTOR in complex 1 DOES NOT have growth factor?

A

Active Tsc2 > inactive Rheb > inactive mTOR =

NO CELL GROWTH

419
Q

What happens to mTOR in complex 1 when it has growth factor present?

A

Active PI 3 kinase > active Akt > active Tsc2 > active Rheb > active mTOR=

Cell growth!

420
Q

What is the role of JAK in regards to cytokines?

A

When a Cytokine binds to its receptor and JAK is there - you get cross phosphorylation and a dimer forms

It activates the kinase associated with the receptor!

421
Q

What is the role of STAT in regards to cytokines?

A

Forms a dimer - only if phosphorylated by JAK

Dimer form =‘effective nucleur localisation signal = can pass through nucleur pore complex and associate with specific sequence

Associate with GTFs > forms mediator complex > turns ON gene transcription

Eg - BCL2 containing proteins that either induce or protect from apoptosis

422
Q

Phosphorylated tyrosines on RTKs serve as … for intracellular signalling proteins

A

Docking sites

423
Q

What is a mutant tyrosine kinase domain?

A

Means that despite getting the signal and the 2 molecules coming together, it CAN’T become activated!

Means there no phosphorylation and no docking sites are generated

424
Q

How do mutant tyrosine domains work in a dominant negative manner?
How is this problematic?

A

One copy stops the receptor from being activated at all, so cannot pass on ANY signal from this receptor!

Problematic: failure to induce proliferation to fight off infections etc

Problematic: receptor could be constantly turned on > induces lots of proliferation > could generate cancer etc

425
Q

What is cholesterol?

A

A versatile molecule with a rigid steroid ring structure, a tail and a hydroxyl group

426
Q

What does uptake of all lipids from the diet require?

A

Requires emulsification (which needs bile acids) and formation of chylomicrons for transport to the liver for processing

427
Q

What is the effect to the liver of bile acids that are NOT bound to lipid droplets?

A

Can be toxic to the liver

Their binding to nuclear hormone receptors enables them to increase expression of enzymes that will degrade them through a transcriptional mechanism

428
Q

What do lipoproteins generated by the liver do?

A

Enable transport of lipids around the body to tissues where it can be stored or used.

They use the amphipathic nature of some lipids to envelop those without this property

429
Q

What does the contents of outside the lipoproteins dictate?

A

Where the particles are destined for

430
Q

Why are interactions between the components of the cell membrane essential?

A

Essential to maintain its integrity and prevent the cell from dying

431
Q

What are the components of the cell membrane?

A

Phospholipids - polar head and long fatty acid tails

Cholesterol - important for maintaining fluidity of membrane

Protein

Glycoprotein

Glycolipid

432
Q

Components of the cell membrane are amphipathic
What does this mean?

A

Both lipid loving and water loving > lipophilic and hydrophilic

433
Q

What do unsaturated fatty acids contain?

A

A 30 degree kink - means other FA can’t be next to it > means solution is more fluid!

434
Q

Why are phos. Serine and phos. Amine on the INSIDE of the membrane?

What’s on the outside of the lipid bilayer?

A

They are negatively charged! There’s an overall electron negative charge on inside of membrane

Phos.choline and sphingomylein are on outside

435
Q

Some cells have more cholesterol than others.
Why do erythrocytes have a ratio of phospholipids: cholesterol of 1:1?

A

Need to have a concave shape > so need to be good at maintaining shape > strong, resilient

So needs a LESS fluid membrane than hepatocytes of liver etc

436
Q

Properties of cholesterol (sterol)?

A

4 ring ridged structure at the centre - makes molecule inflexible!

Saturated hydrocarbon tail - Van der Waals forces with phospholipids around it

437
Q

Cholesterol is used to generate Bile acids

Why is this important?

A

Important in digestion > in encouraging the breakdown of lipids

438
Q

What is the rate limiting step in production of cholesterol?

What happens is there’s a single base change ( a variant) in HMG reductase?

A

HMG CoA reductase - controls how quickly cholesterol is generated and therefore things like steroid hormones, fat soluble vitamins and bile acids

HMG reductase will work faster than normal! Generates excess amount of cholesterol > eg in people that have hypocholesterolaemia

439
Q

Properties of bile acids / salts?

A

Synthesised from cholesterol

Essential for lipid digestion

Increase solubility

Increase surface area - increase rate of reaction + rate of digestion

440
Q

Primary bile acids are quite reactive and very toxic so are converted to to less reactive and less toxic secondary bile acids.
What is the effect of this conversion / conjugation?

What problems could highly toxic primary bile acids cause in the liver?

A

Additions / conjugation increases solubility > need things to be hydrophilic to get rid of them from body

Could cause Colistasis in the liver - bile build up

441
Q

Myocyte?

Adipocyte?

A

Cardiac cells > need lots of energy

Storage

442
Q

The gallbladder stores bile ready for release.
How does it do this?

A

First it concentrates it for storage and then dilutes it in response to fats detected in the small intestine through release of cholecystokinin CKK

443
Q

Bile acids can be modified by conjugation. What is this?

It makes the original product…

A

The formation of a link between an amino acid with a waste or toxic product

Less toxic
More hydrophilic + soluble
Easier to excrete

444
Q

What is the effect of cholesterol + saturated fatty acid tails?

A

It will make the phospholipid bilayer more rigid = stiffening effect

445
Q

What happens in bilayers where there are lots of UN- saturated fatty acid tails in phospholipids?

A

Cholesterol will make the bilayer more fluid

446
Q

What are the main ways for phospholipids to be dynamic in the membrane?

A

Lateral diffusion, flexion, rotation - occur without enzyme activity > most frequent

Flip flop - rarely occurs unless it is enabled by an enzyme / channel

447
Q

Saturated FA tails + phospholipids =

A

Thicker membrane > more stability > rigid

448
Q

Un saturated FA tails + phospholipids =

A

Slightly thinner membrane > less stable > more fluid

449
Q

Why is there lots of phos. Choline in the liver?

A

There’s a large surface area there > hepatocytes have lots of exchange > so need fluid membranes to have fast transport over membrane

450
Q

Why is phos. Serine relatively low in all cells and organelles?

A

As it is negatively charged on inside of membrane > maintains electrostatic interaction

May appear on the outside of membrane if platelets are activated

451
Q

Why does Myelin have lots of phos. Ethanolamine and cholesterol?

A

It insulates nerves and allows Saltatory conduction > needs to be thick

452
Q

Why do mitochondria and ER have different ratios of lipid components?

A

Cholesterol increases as move out towards cell membrane > mitochondria doesn’t have much > doesn’t need to be rigid, just needs to form barrier

RER needs to be more rigid as ribosomes will be making proteins and transporting

453
Q

What are lipid rafts?

A

Collections of lipids brought together by cholesterol

454
Q

Properties of lipid rafts?

When are they used?

A

Acts as an anchor for proteins
Prevent movement of membrane components around ‘fluid mosaic’ membrane > reducing movement and diffusion

Require location specific functions - eg receptors need to be in synapse
Contain specific protein subunits - eg associate in membrane to be activated

Makes sure membrane components are physically close to interact - otherwise won’t be functional!

455
Q

What is cell polarity?

(Affects lateral diffusion)

A

Essential that the cell knows where up/down and inside / outside is

Needs to be some kind of barrier to stop too much diffusion otherwise they will mix up areas of the membrane > eg Tight Junctions - rigid structures that are a big obstacle to any movement

456
Q

Confocal microscope

A

Can start to focus at lots of different places throughout the cell!

Can see whole of the cell in little segments

Can make a 3D rendition

457
Q

What’s happens to propidium iodide (lipophilic dye) when it moves into cell and the cell is alive?

When the cell is struggling to survive?

A

Alive - immediately kicked out by ATPases

Struggling to survive - prop iodide can’t exit cell > flipase and flopase are turned off so can’t get rid of it > cell death!

458
Q

Annexin V (binds phospatidylserine) only has access to the outside of membrane > can’t move across as it is NOT lipophilic

What does it show in early vs late apoptosis?

A

Early - still some phos. Serine on the outside > Sramblase turned on > still some ATP as low concentration of prop iodide > flipase and flopase control levels

Late - large volumes of prop iodide and phos. Serine (lots of dye stained) > BAD > ATP no longer abundant > cells definitely going to die > phos. Serine in the outside and prop Iodide NOT kicked out!

459
Q

Modification changes enable the activation of enzymatic function or recognition by another protein.

Methods include:

A

Phosphorylation - negative charge changes properties of + charged AA

Acetylation - prevents other things activating protein

Methylation - same as acetylation

Cleavage - cutting longer AA sequence into shorter one to = activated protein

460
Q

Protein … and … are employed in virtually all signalling pathways

A

Kinases
Phosphatases

461
Q

What is the process of a simple signalling cascade?
(1 kinase and 1 target protein)

A

Ligand will only bind receptor if BOTH parts of binding sites are present

When it binds ligand there is shake change in receptor

Kinase domains are now closer together =ACTIVE. Are able to start phosphorylating things

It can phosphorylate a protein > changes the proteins shape > can dimerise with 1 other protein

Go into nucleus as proteins have nuclear localisation signal > can activate gene expression > bind DNA > stimulate transcription

Nuclear phosphatase in nucleus will de phosphorylate proteins = INACTIVE

Moves out into cytoplasm to repeat process

462
Q

What are the 3 methods to ensure transmission of a signal?

A

Scaffolding

Docking sites

Complex formation

463
Q

The domino effect amplifies extracellular signals - what does it enable?

A

Activation of multiple pathways to induce multiple effects simultaneously

Convergence of multiple pathways on a single target

464
Q

Ion channel receptors

A

Form a pore in membrane

Only open when it’s signal particle is bound to protein

Restrict movement of ions from one side of membrane to another

465
Q

G protein receptors

A

7 transmembrane domain containing proteins embedded in membrane

4 flavours

466
Q

Enzyme coupled receptors

A

Single pass transmembrane receptors that ‘dimerise’ in membrane in response to ligand binding

Activate eachother to recruit intracellular proteins

Often result in use of secondary messengers

467
Q

Ion channel receptor examples

A

Nicotinic Acetyl choline receptors - cation channels, mostly K+ and Na+

GABA receptors - inhibitory NT (nerve terminus), chloride channel, hyper polarises cell

468
Q

What do trimeric G proteins do?

A

Relay signals from GPCRs

469
Q

How are G proteins activated by activated GPCRs?

A

Binding of ligand to GPRC leads to displacement of GDP from the inactive trimeric G protein complex

Binding of GTP to the trimeric G protein leads to its activation and dissociation into a, b and y subunits

470
Q

What does phospholipase C metabolise?

A

Phosphorylated lipids such as PIP2

PIP2 is needed for adaptor proteins to bind so we can get Clathrin binding
Needed for things that associate with Dynamin

471
Q

What is PIP2 hydrolysed into?

A

IP3 - releases Ca2+ from the ER

DAG - activates protein kinase C

472
Q

How are adenylyl Cyclase, cAMP and protein kinase A (PKA) related?

A

When low levels of cAMP are present, protein kinase A is inactivated by binding of regulatory subunit

When adenyl Cyclase activated and produces cAMP, [cAMP] increases

PKA has greater affinity for cAMP than the regulatory subunit so cAMP binding then releases inhibitory subunit and PKA becomes active!

Activated PKA can move into nucleus and phosphorylate CREB etc which controls transcriptional activation of gene promoters

473
Q

What are receptor tyrosine kinases?

A

Directly phosphorylate specific tyrosine residues on receptor itself and on other intracellular proteins

474
Q

When a protein , amino acid or peptide ligand binds to its receptor a …

A

Second messenger molecule is activated

475
Q

G proteins are active when …

A

GTP is bound

476
Q

What uses local signalling methods?

A

Neurotransmitters

477
Q

A hormone released from a cell into the blood is found in what type of signalling?

A

Endocrine

478
Q

Water soluble hormones act on…

A

Cell surface receptors

479
Q

Hormones cause multiple responses by…

A

Using multiple receptors

Causing different cellular responses

480
Q

Hormone pairs with opposite effects are called…

A

Antagonistic pairs

481
Q

Ligand gated ion channels are specific for …

A

The ligand and the ion type

482
Q

Synaptic signalling involves …

A

Releasing hormones form a neuron

483
Q

Steroid hormones are located…

A

Inside the cell

484
Q

Membrane is synthesised in the …

A

SER

485
Q

New membrane is …

A

Symmetrical

486
Q

Vesicles are used to transport new membrane to the Golgi
What do they use as a coat protein?

A

COP2

487
Q

Membrane moving OUT to the plasma membrane uses what as a coat protein?

A

Clathrin

488
Q

The PLASMA membrane is…

A

Asymmetrical

489
Q

In the OUTER leaflet you find…

A

Phos. Choline and Sphingomyelin

490
Q

In the inner leaflet you find…

A

Phos. Serine and phos. Ethanolamine

491
Q

Scramblase is a protein that moves phospholipids between layers.
What ion is it dependant on?

A

Ca2+

492
Q

During activation of Apoptosis, phospholipids move in the membrane because …

A

Calcium release activated scramblase action

493
Q

Anaerobic metabolism of glucose is important under the following conditions / situations?

A

Anaerobic bacteria

Exercising muscle (oxygen limitation)

Ethanol metabolism (yeast)

Hypoxia (humna eg heart attack)

Some cancers

494
Q

What tissues can store glycogen?

A

Liver - up to 200g

Skeletal muscle - up to 300g

495
Q

The erythrocytes produce lactate. Why?

A

The LACK mitochondria, therefore cannot undertake aerobic glycolysis

496
Q

Forgut metabolisers eg cows have bacteria in the foregut that metabolise cellulose and glucose.
What is the main disadvantage for the cow?

A

The cows have to convert the volatile fatty acids (products of bacterial glucose metabolism) into glucose via gluconeogenesis

497
Q

Foregut metabolisers eg cows have bacteria in the forgut that convert glucose into volatile fatty acids.
What are the potential advantages?

A

The cows forgut contains bacteria that secrete Cellulase

The bacteria produce vitamins and amino acids that the cow can utilise

The bacteria remove toxins

498
Q

Glycolysis: what phase

A) provides 2 net ATP molecules

B) utilises 2 ATP molecules

C) provides 4 ATP molecules

A

A) the overall pathway

B) the preparatory phase

C) the pay off phase

499
Q

The enzyme pyruvate kinase is INHIBITED by Acetyl CoA.
What is Acetyl CoA a product of?

A

Fatty acid beta oxidation pathway

500
Q

The metabolic fate of pyruvate can include the following DIRECT products:

A

Lactate under anaerobic conditions

Lactate under hypoxia conditions

Volatile fatty acids by bacteria in the rumen of cows

Oxaloacetate under gluconeogenic conditions

Ethanol in yeast under anaerobic conditions

Acetyl CoA under aerobic respiration conditions

501
Q

Identify the glucose sparing pathways

A

Glucose alanine cycle

Cori cycle

502
Q

The Hexokinase enzyme utilises ATP as a co substrate.
Identify the functions of ATP in this reaction:

A

Donates an inorganic phosphate Pi

Hydrolysis of ATP to ADP provides energy to drive the reaction from glucose to glucose 6 phosphate

503
Q

The Hexokinase enzymes utilise Mg2+ as a co substrate.
Identify the functions of Mg2+ in this reaction

A

It helps correctly orientate the substrates

It helps to reduce electrostatic charge, thus electrostatic repulsion

504
Q

In anaerobic glycolysis (lactate production), no NADH is produced. Why?

A

NADH is produced in the conversion of glucose to pyruvate
But NADH is utilised in the conversion of pyruvate to lactate

505
Q

What characteristics apply to Hexokinase 1?

A

Ubiquitous expression

Broad specificity for hexose monosaccharides

Product inhibition

Hyperbolic kinetics

Low km and vmax for glucose

Catalyses an irreversible reaction - ie uni directional

Is a control point in glycolysis!

506
Q

Identify metabolic indicators of high energy status in the cell

A

ATP

Citrate - utilised in TCA cycle

507
Q

Conversion of fructose 6 phosphate to fructose 2,6 bisphosphate is catalysed by what enzyme?

A

Phosphofructokinase 2 - PFK2

508
Q

Allosteric compounds can be identified by…

A

Sigmoidal kinetics

509
Q

Identify the enzyme products that are controlled directly by the insulin / glucagon ratio

A

Fructose 2,6 bisphosphate

Pyruvate

510
Q

What ONLY applies to liver pyruvate kinase? L PK

A

Activation by insulin action

511
Q

The 2nd most common form of enzyme linked haemolytic anaemia is caused by deficiency in the … enzyme

A

Pyruvate kinase

512
Q

What metabolites are NOT substrates for gluconeogenesis in humans?

A

Long chain fatty acids

Acetyl CoA

513
Q

In glycolysis there are 3 uni directional (irreversible) enzyme catalysed reactions that are bypassed by … in gluconeogenesis

A

4

514
Q

What proteins and enzymes are involved in the hydrolysis of glucose 6 phosphate to glucose, and the transport of the latter out of the cell?

A

Glucose 6 phosphate

Glucose 6 phosphate transporter

GLUT 2

GLUT 7

515
Q

Pyruvate is a substrate for gluconeogensis.
During this is is NOT derived from…

A

Glucose

Beta oxidation of fatty acids

516
Q

What statement relating to pentose phosphate pathway is NOT correct?

A

The ppp provides NADPH for energy production

517
Q

The primary point of regulation in the pentose phosphate pathway is…

A

The glucose 6 phosphate dehydrogenase enzyme

518
Q

What intermediate in the pentose phosphate pathway is utilised for the synthesis of aromatic amino acids?

A

Erythrose 4 phosphate

519
Q

What molecule is a free radical?

A

O2 -

520
Q

What are the protective mechanisms against oxidative stress?

A

Glutathione peroxidase

Superoxide dismutase SOD

Vitamin C

Vitamin E

521
Q

GSH reduced glutathione is oxidised to GSSG oxidised glutathione by…

A

Glutathione peroxidase

522
Q

The cytochromes P450 are …

A

Phase 1 drug metabolising enzymes

523
Q

Glucose 6 phosphate dehydrogenase deficiency…

A

Is linked to haemolytic anaemia

Provides resistance to malaria

Is the most common form of enzyme linked haemolytic anaemia

Causes neonatal jaundice

524
Q

What are the 8 mechanisms of membrane insertion?

A

Single pass proteins

Multi pass proteins

Channel

Not membrane spanning but embedded in the membrane

Lipid anchored

Glycolipid anchored

Adaptor proteins

Accessory proteins

525
Q

What are lipid anchors?

A

Rely on interactions between FA chain and phospholipid tails

Raft formation ensures proximity to transmembrane proteins

All have LONG CHAIN fatty acid tails > easily integrates into membrane next to FA tails of phospholipids > longer they are, better the anchor > more van der waals forces

526
Q

Myristoyl anchor

A

Large number of carbons

Amide linkage > attaches lipid to N terminus (NH group)

527
Q

Palmitoyl anchor

A

Attached by a thioester linkage to sulphur group (present on cysteine AA)

Benefit: can be anywhere! N or C terminus, OR in the middle > versatile

528
Q

Farmesyl anchor

A

Thioester linkage to C terminus

C=O group

Unsaturated FA > fits in better than saturated

529
Q

How are proteins inserted into the membrane?

A

Polypeptide chain needs to form cylindrical structure allowing charged / polar AA to be hidden from hydrophobic middle of the bilayer > otherwise helix can’t be embedded in membrane

Uncharged / NON polar AA on outside of cylinder enable interaction with fatty acid tails

ER will check that all hydrophobic AA are on outside and hydrophilic on inside!

530
Q

What is the Hydropathy Index?

A

The measure of how hydrophobic (or not) something is!

The further up on the scale > the MORE hydrophobic it is and the further down > the least hydrophobic it is!

Below the line on the index > in the cytoplasm OR outside of the cell > aqueous environment > very hydrophilic

531
Q

What is the function of a selectivity filter?

A

Charges and polarity in the centre of the pore in the channel makes it selective for its ligand!

532
Q

What gives membranes strength?

A

Spectrin heterodimers form a mesh using junctional complexes

Junctional complexes formed from short actin filaments

Cytoskeleton is linked to membrane through 2 transmembrane proteins, band 3 and glycophorin > provide way of keeping membrane in certain orientation + give the ability to stand up to some flexion > scaffold!

533
Q

How is membrane movement controlled?

A

A domain is formed if there is a physical blockage to movement

Lateral diffusion is possible within a domain of the membrane

Tight junctions are an example as they restrict movement within the bilayer > they require multiple proteins > makes sure there’s a mono-layer of plasma membrane > enables diffusion within the domain at the top but DOESN’T allow diffusion down the sides

534
Q

How is diffusion limited in the membrane?

A

The cortical cytoskeleton network restricts diffusion of plasma membrane proteins directly anchored to it

Cytoskeletal filaments form mechanical barriers that obstruct free diffusion > partitioning them into small domains

Proteins diffuse rapidly but are confined within an individual domain

Transmembrane proteins associated with many other proteins are limited in their diffusion depending on interactions between them and size of its cytoplasmic domain

535
Q

What is the benefit of the formation of domains?

A

Helps concentrate signalling complexes, increasing the speed and efficiency of the signalling process

Domains can be permanent (spermatozoa) or transient

In cells with several structurally and functionally distinct parts, rafts enable domains of the membrane to form that contain specific proteins - eg in spermatozoa

536
Q

Glycolipids

A

Made of a diglyceride attached to a carbohydrate

Diglyercide acts as the anchor

Immune recognition

Involved in determination of self / blood groups

Important in surveillance of cells and tissues by macrophages + T cells > checking there aren’t any foreign particles like bacteria or viruses

537
Q

Glycoproteins

A

Usually part of complex, multi subunit receptors

Carbohydrate chain acts to restrict movement or scaffold structures

Eg - proteoglycans > essential for interaction with extracellular matrix

538
Q

What are the functions of glyco-additions?

A

Support interactions of a receptor with its ligand

Can act as part of ligand recognition site

539
Q

Exocytosis

A

Vesicle moves to membrane and releases its contents

540
Q

Endocytosis

A

Sampling the extracellular environment > takes something up > ‘budding’ process in reverse > invagination of membrane > takes things up from outside

541
Q

What is the donor compartment?

A

Where cargo is and receptors that are needed to package vesicle

Cargo associates with receptors > signals that there should be a bud forming

‘Budding’ process leads to production of vesicle

542
Q

Vesicle transport

A

Donor compartment first

Vesicle is going towards target membrane

Knows where it needs to go based on coat and snare proteins

Vesicle fuses with membrane and fusion happens

Contents of vesicles get released out into target compartment

543
Q

What do glyco additions like Mannose enable?

A

Receptor binding and direct transport to specific compartments

544
Q

Directions of movement for coat proteins: COPI, COPII and Clathrin

A

COPI - goes from Golgi to ER

COPII - goes from ER to Golgi

Clathrin - involved in uptake of things from outside of cell by endocytosis from plasma membrane into early endosome OR from some parts of Golgi out to endosome

545
Q

Lipids and compartments SUMMARY

A

Contents of membrane can be regulated by endocytosis and exocytosis

Membrane components made in ER contain LOW levels of cholesterol, increasing as membrane matures through Golgi to plasma membrane

Membrane bound proteins generated in ER can act as cargo receptors

Vesicular transport enables secretory proteins and membrane bound proteins to be transported to plasma membrane while also allowing Retrograde Transport into the cell of extracellular environment, membrane recycling and receptor recycling and degradation

546
Q

Structure of Clathrin coats

(Only recruited to receptors associated with plasma membrane)

A

Each Triskelion is composed of 3 Clathrin heavy chains and 3 light chains

Light chains attach to cytoskeleton and is how the bending process starts!
Because it requires an adaptor protein to bind to cytoskeleton that’s inside and helps generate a force due to its shape!

Triskelion made of proteins > some AA in these will be charged > charge will help to bend membrane

547
Q

Coat formation steps

A

Coat assembly and cargo selection - proteins in ER membrane act as receptors to keep cargo in specific place. Binding leads to conformational change that enables adaptor proteins to be recruited

Bud formation - adaptor proteins (eg AP2) bind to Clathrin Triskelions.
Bar domain containing proteins aid the bending of membrane to increase access to adaptor proteins to Clathrin

Vesicle formation - continuation of formation of a vesicle and generation of a stalk > then recruits Dynamin and accessory proteins to pinch off vesicle

Uncoating - after vesicle released, there is NO longer need for coat proteins and associated proteins, so they are disassembled and recycled.
This leaves the vesicle with cargo bound receptors on vesicle surface > and snare proteins to direct the vesicle to its destination

548
Q

Initiation of coat formation

A

Adaptor protein AP2 is made up of different subunits: B2, u2, o2.

Binding of u2 and o2 needs to bind PIP2 to initiate cargo receptor binding

PIP2 binds > changes shape > flips subunit around > unlocks it > AP2 now open

Change in receptor conformation leads to membrane deformation, making it more accessible for coat proteins

549
Q

Coat proteins need help to bend the membrane

A

Membrane bending proteins that contain BAR domains cause a shape change to membrane via electrostatic interactions with lipid head groups

BAR domain proteins are thought to help AP2 recruit Clathrin by shaping the plasma membrane to allow Clathrin costed bud to form

Some proteins contain Amphiphilic helices that causes membrane bending when inserted into cytoplasmic leaflet

These are essential to shaping the neck of budding vesicle through stabilisation of sharp membrane bends

Clathrin machinery recruits local assembly of actin filaments that introduce tension to help pinch off and propel the forming vesicle away from the membrane

550
Q

Vesicle release

A

Dynamin recruits a protein complex to initiate vesicle release

Inner leaflet of the bilayer merge, then the vesicles pinches off

551
Q

Dynamin

A

GTPase domain > will cleave GTP to GDP. If associated with GDP = relaxed structure.
If exchanged to GTP > squeezes the neck of budding vesicle as it contracts > which hydrolyses GTP into GDP again.
GDP will fall off, Dynamin relaxes and process repeats

Dynamin had PIP2 binding site as well! So PIP2 used for recruitment of Dynamin and to allow adaptor proteins to bind to Triskelion

552
Q

Rab proteins and their role

A

Single protein monomeric GTPases > associate with GDP when not active and GTP when ACTIVE

As vesicles approaches, there is tethering > Rab recognises Rab effector and guides it in

Rab effector then changes shape to guide it to where snare is

T snare and V snare are complementary to eachother = Trans snare complex. Bring the membranes close together to cause fusion.

Rab GDP is then recycled, binds to Rab GDP inhibitor that stops it from working until it becomes associated with vesicles again!

Cargo then released into target compartments

553
Q

Lipid droplets

A

Triaglycerols and cholesterol esters

Generation of cholesterol through HMG CoA reductase > resident in the ER

Products are NOT amphipathic > therefore need to be coated in membrane to enable transport through the aqueous cytosol

Lipids are NOT hydrophilic so only need a single coating of membrane

554
Q

LDL uptake

Excess LDL can control cholesterol synthesis in the liver. The detection system is as follows:

A

Endocytosis of LDL particles using Clathrin coated pits

Recycling of LDL receptors to plasma membrane

Formulation of a vesicle containing cholesterol esters which is integrated into ER

High cholesterol levels in ER results in a decrease in the synthesis of HMG CoA reductase and LDL receptors

555
Q

Vesicle transport SUMMARY

A

Organelle and membrane makeup can be regulated by endocytosis and exocytosis

Donor compartments require specific lipids (PIP2) to encourage recruitment of adaptor proteins to loaded cargo receptors during bud formation

Recruitment of cost protein and associated BAR domain containing proteins bends the membrane to generate a vesicle which is released with the help of Dynamin

Monomeric GTPases such as Rab hell to ensure the vesicles reaches its target. With its complementary Rab effector enables docking on target membrane to enable SNARE proteins to cause membrane fusion

Endocytosis and exocytosis can be observed in the regulation of lipoprotein and cholesterol levels in the body through the LDL receptor feedback system

556
Q

Membrane asymmetry

A

Incoming vesicles to cell surface are randomly sorted = problem

At cell surface there is phos ethanolamine and phos serine on the inner leaflet

Scramblase is in the ER and ensures that there is the same number of phospholipids on outer leaflet as the inner leaflet

Glycolipids are on outer leaflet for cell recognition

557
Q

Dealing with membrane asymmetry

A

Enzymes are required to ensure that membrane phospholipid addition occurs EQUALLY on both leaflets of the bilayer

558
Q

Scramblases

A

Calcium dependant enzymes

Enables movement of phospholipids from inner to outer leaflet of plasma membrane

Calcium will activate enzyme > allow it to change shape so it can move things from 1 side to the other
Lots of Calcium in the ER > means scramblase is turned ON most of the time!
Calcium concentration in plasma membrane is low > is not turned on under normal circumstances

559
Q

Scramblase action

A

Important in apoptosis

Maintains mitochondrial membrane function

In apoptosis, ER is compromised in integrity. So releases large volumes of calcium from ER into cytoplasm. When calcium levels increase in cell, it activates scramblase.
Problematic as it allows phos serine to move to outer leaflet > it is negatively charged > means -ve charge is on outside of membrane instead!
Problematic for mitochondria, cells can’t survive in this environment, no ATP etc

560
Q

Flippase and floppase

A

A helical structure

Part of flippase family of proteins

ATP binding cassette transporter protein

561
Q

Flippase and floppase action

(Very specific)

A

Flippase - moves anything that is phos serine and phos ethanolamine onto the inner leaflet

Floppase - moves other 2 phospholipids out to the outer leaflet / external surface

So creates membrane asymmetry!

ATP is essential for their function > problem if there’s no ATP, means flippase and floppase can’t correct Scramblase action > disrupts membrane symmetry > membrane compromised > disrupts cell function > APOPTOSIS

562
Q

What is the compound Fluorodeoxyglucose used for?

A

Detection of cancer tumours, using positron emission tomography PET

563
Q

List the characteristics of Hexokinase 4

A

Catalyses an irreversible reaction (uni directional)

Is a control point in glycolysis

Fructose 6 phosphate is an allosteric inhibitor

Broad specificity for hexose monosaccharides

Sigmoidal kinetics

Activity is controlled by a regulator protein

High KM and vmax for glucose

Expressed in the liver and pancreas

564
Q

What hormone is linked to the feeding response and increases utilisation of glucose?

A

Insulin

565
Q

What products are produced during the pay off phase of glycolysis?

A

2x pyruvate

4x ATP

2x NADH

566
Q

What are the products of the reaction catalysed by PFK1?

A

Fructose 1,6 bisphosphate

567
Q

The conversion of fructose 6 phosphate to fructose 2,6 bisphosphate is catalysed by what enzyme?

A

PFK2

568
Q

Elevated levels of glycolysis in tumour cells are due to the …

A

Warburg effect

569
Q

Allosteric compounds can be identified by …

A

Sigmoidal kinetics

570
Q

Glucagon activates the … enzyme

A

FBPase 2

571
Q

What are the metabolic roles for NADPH

A

NADPH oxidase (phagocytosis)

Reductive biosynthesis

Phase 1 drug metabolism

Reduction of hydrogen peroxide

Nitric oxide synthesis

572
Q

In the synthesis of fatty acids, the addition of a 2 carbon unit requires …

A

2 NADPH

573
Q

What are the protective mechanisms against oxidative stress?

A

Superoxide dismutase SOD

Vitamin C

Glutathione peroxidase

Vitamin E

574
Q

Regarding the G6PD enzyme, NADPH is a…

A

Product and product inhibitor!

575
Q

What intermediate in the PPP is utilised for synthesis of nucleic acids?

A

Ribose 5 phosphate

576
Q

When fats are ingested in the diet …

A

Bile salts emulsify dietary fats in the small intestine, forming mixed micelles

Intestinal lipases degrade triaglycerols

Fatty acids and other breakdown products are taken up by the intestinal mucosa and converted into triaglycerols

Triaglycerols are incorporated with cholesterol and apolipoproteins into chylomicrons

Chylomicrons move through the lymphatic system and bloodstream to tissues

Lipoprotein lipase activated by apoC II in the capillary, converting triaglycerols to fatty acids and glycerol

Fatty acids enter cells

Fatty acids are oxidised as fuel or re esterified for storage

Biochem - YEAR 2 (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions