Brainscape's Knowledge GenomeTM

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


See full index

MEH > Session 2 > Flashcards

Session 2 Flashcards

1
Q

What are the tissues with an absolute requirement for glucose?

A
  • Red blood cells
  • Neutrophils
  • Innermost cells of kidney medulla
  • Lens of the eye
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

At what concentrations of blood glucose do symptoms occur?

A

Normally held at around roughly 5mmol/L

  1. 8mmol/L. Confusion
  2. 7mmol/L weakness, nausea
  3. 1 mol/L muscle cramps
  4. 6mmol/L brain damage, death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is glycogen stored?

A

Glycogen is stored as granules.

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

What happens to proteins when glucose concentration in the blood is too high?

A

They react with the glucose and become glycosylated and alters function

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

What are the two main stores of glycogen in the body?

A

Liver (roughly 100g) and muscles (roughly 300g)

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

What is the difference between glycogen stored in the liver and glycogen stored in the muscles?

A

Glycogen in the liver can be used to replenish blood plasma glucose whereas in the muscles it is trapped only to be used there.

In the liver:
G6P converted to glucose and exported to blood. Liver glycogen is a buffer of blood glucose levels.

In the muscles:
Muscle lacks the enzyme Glucose-6-phosphatase. G6P enters glycolysis for energy production.
Muscle glycogen stores differ in that Glucagon has no effect.
Also AMP is an allosteric activator of muscle glycogen phosphorylase but
not of the liver form of enzyme

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

Describe the structure of glycogen

A
  • Glycogen is a polymer consisting of chains of glucose residues
  • Chains are organized like the branches of a tree originating from a dimer of the protein glycogenin (acts as a primer at core of glycogen structure).
  • Glucose residues linked by α-1-4 glycosidic bonds with α-1-6 glycosidic bonds forming branch points every 8-10 residues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the benefits to storing glucose as glycogen in the way that we do?

A

Highly branched so many points for enzymes to cleave off glucose molecules. By storing it as a macromolecule it significantly reduces its osmotic effects so water isn’t drawn into the cell.

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

What is glycogenesis? Explain how it works

A

Glycogen synthesis

  1. A glucose molecule reacts with an ATP molecule to form glucose-6-phosphate and an ADP molecule. This is requires hexokinase or (glucokinase in the liver).
  2. Glucose 6-phosphate is converted to phosphoglucomutase.
  3. Glucose 1-phosphate + UTP + H2O forms UDP-glucose + PPi. This reaction is carried out by G1P uridyltransferase.
  4. Glycogen(n residues) + UDP-glucose forms glycogen(n+1 residues) + UDP. The enzymes for this are Glycogen synthase (α-1-4 Glycosidic bonds) or branching enzyme (α-1-6 Glycosidic bonds).

Synthesis of glycogen requires energy.

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

What is glycogenolysis? Explain how it works

A

Glycogen degradation
Not a simple reversal of glycogenesis.
1. Glycogen(n residues) + Pi forms glucose 1–phosphate and Glycogen(n-1 residues). This reaction requires glycogen phosphorylase (α-1-4 Glycosidic bonds) or de-branching enzyme(α-1-6 Glycosidic bonds).
2. Glucose 1-phosphate is converted to glucose 6-phosphate using phosphoglucomutase.

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

Draw and annotate a diagram giving an overview of glycogen metabolism

A

Insert image

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

What is the rate limiting enzyme of glycogen synthesis in the liver?

A

Glycogen synthase

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

What is the rate limiting enzyme of glycogen degradation in the liver?

A

Glycogen phosphorylase

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

Explain regulation of glycogen metabolism in the liver

A

Occurs in reciprocal fashion. Insert table

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

How do glycogen storage diseases arise?
What effects would they have?
Give examples

A

Inborn errors of metabolism (inherited diseases)
Arise from deficiency or dysfunction of enzymes of glycogen metabolism
• Liver and /or muscle can be affected
• Excess glycogen storage can lead to tissue damage
• Diminished glycogen stores can lead to hypoglycaemia & poor exercise tolerance.
Examples:
Examples: • von Gierke’s disease -glucose 6-phosphatase deficiency
• McArdle disease - muscle glycogen phosphorylase deficiency

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

What is gluconeogenesis and when does it occur?

A

The production of new glucose
Beyond ~ 8 hours of fasting, liver glycogen stores start to deplete and an alternative source of glucose is required: Gluconeogenesis

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

Where does gluconeogenesis occur?

A

Occurs in Liver and to lesser extent in Kidney cortex

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

What are thee three major precursors for gluconeogenesis?

A

Lactate - From anaerobic glycolysis in exercising muscle and red blood cells (Cori cycle) (insert pic)

Glycerol - Released from adipose tissue breakdown of triglycerides.

Amino acids - Mainly alanine.

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

Can glucose be synthesised from acetyl-CoA

A

Acetyl-CoA cannot be converted into pyruvate (pyruvate dehydrogenase reaction is irreversible) so there is no net synthesis of glucose from acetyl-CoA

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

What type of receptor does insulin bind to?

A

Tyrosine kinase receptor

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

From what family of receptors does adrenaline and glucagon bind to?

A

GPCR

G protein coupled receptor

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

What are the key enzymes in the gluconeogneseis pathway?

And which two are the majors control sites of the pathway?

A
  1. Phosphoenolpyruvate carboxykinase (PEPCK)
  2. Fructose 1,6-bisphosphatase
  3. Glucose-6-phosphatase

1 and 2 are the majors control sites of the pathway.

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

What factors do the enzymes involved in regulation of gluconeogenesis respond to?

A

Starvation/fasting
Prolonged exercise
Stress

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

What are the two enzymes involved in the regulation of gluconeogenesis and how do they regulate it?

A

Fructose 1,6-bisphosphatase
Phosphoenolpyruvate carboxykinase (PEPCK)
Insert table

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

Explain the time course of glucose utilisation

A

Glucose from food - up to roughly to hours. Obtains glucose from feeding
Glygogenolysis -up to 8-10 hours. Uses glycogen
Gluconeogenesis from 8-10 hours onwards. Uses lactate, glycerol and amino acids.

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

How are lipids stored?

A
  • Energy intake in excess of requirements is converted to Triacylglycerol (TAG) for storage
  • TAGs are hydrophobic and therefore stored in an anhydrous form in specialised tissue – adipose tissue
  • Highly efficient energy store. Energy content per gram twice that of carbohydrate or protein
  • Utilised in prolonged exercise, stress, starvation, during pregnancy
  • The storage & mobilisation of TAGs is under hormonal control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How is triacylglycerol formed?

A

Insert pic

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

What are adipocytes?

A

Cells that store fats (mainly TAG and cholesterol ester)
• Typical adipocyte ~0.1mm in diameter. Cells expand as more fat
added
• Average adult ~30 billion fat cells weighing ~15 kg.
• Can increase in size about fourfold on weight gain before dividing
and increasing total number of fat cells

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

How are adipocytes adapted for their function

A

Cytoplasm and organelles pushed to the edge so that there’s more space for storage.

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

Overview of dietary triacylglycerol metabolism

A

Insert image of cycle

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

What is the process called for fatty acid synthesis?

How does it work?

A

Lipogenesis
• Mainly in liver. Dietary glucose as major source of carbon.
• Glucose is turned into pyruvate in cytoplasm (glycolysis).
• Pyruvate enters mitochondria and forms acetyl-CoA & oxaloacetate which then condense to form citrate
• Citrate enters the cytoplasm and is cleaved back to Acetyl-CoA &
Oxaloacetate.
• Acetyl-CoA carboxylase (key regulator) produces
malonyl-CoA from Acetyl-CoA.
• Fatty acid synthase complex builds fatty acids by sequential addition of 2 carbon units provided by malonyl-
CoA.
Process requires both ATP and NADPH

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

Explain liver lipogenesis using a diagram

A

Insert cycle

33
Q

What is the key regulatory enzyme in liver lipogenesis?

A

Acetyl-CoA carboxylase

Insulin (covalent de-phosphorylation), & citrate (allosteric) increase activity

Glucagon / adrenaline (covalent phosphorylation) & AMP (allosteric) decrease activity

34
Q

Give a comparison between fatty acid synthesis and β oxidation in the form of a table

A

Insert table

35
Q

How is fat mobilised and what regulates it?

A

Lipolysis - breakdown of fat.

Hormone sensitive lipase breaks down TAG into glycerol (which travels to the liver to be utilised as a carbon source for gluconeogenesis) and free fatty acids (which travel complexed with albumin to muscle and other tissues for beta oxidation)
Glucagon & Adrenaline leads to
phosphorylation and ACTIVATION of HSL
Insulin leads to de-phosphorylation and inhibition of HSL

36
Q

When someone gains weight to become obese what is the type of fugue that changes?

A

Triacylglycerol (TAG) increases whereas the others stay pretty much the same.

37
Q

Why are lipids difficult to transport?

A

They are a structurally diverse group of compounds and they’re hydrophobic so insoluble in water making it difficult to transport in blood.

38
Q

How are lipids transported?

A
  • ~ 2% of lipids (mostly fatty acids) carried bound to albumin but this has a limited capacity (~ 3 mmol/L)
  • ~ 98% of lipids are carried as lipoprotein particles consisting of phospholipid, cholesterol, cholesterol esters, proteins & TAG
39
Q

What are the typical plasma lipid concentration ranges?

A 
Triacylglycerol 0-2.0 mmol/L
Phospholipids roughly 2.5 mmol/L
Total cholesterol <5.0 mmol/L
Cholesterol esters roughly 2.5 mmol/L
Free fatty acids 0.3-0.8 mmol/L
Total Lipids 4000-8500 mg/L
40
Q

Describe the structure of phospholipids and how they’re classified.

A

They have a polar head that is hydrophilic and non polar tails made from fatty acids. The tails are hydrophobic. Glycerol centre.
Classified according to their polar head group e.g.:

Choline head makes phosphatidylcholine

Inositol head makes phosphatidylinositol

41
Q

What important structures can phospholipids form?

A

Liposome (double phospholipid layer with core)
Micelle (single phospholipid layer with core)
Bilayer sheet

42
Q

Why are liposomes useful?

A

Can facilitate the existence of a different environment in the core

43
Q

Where does cholesterol come from and what is it used for?

A

• Some cholesterol obtained from diet, but most synthesised in liver
• Essential component of membranes (modulates fluidity)
• Precursor of steroid hormones
Cortisol
Aldosterone
Testosterone
Oestrogen
• Precursor of bile acids
• Transported around body as cholesterol ester.
Transport is esterified using a fatty acid by lecithincholesterol acyltransferasee (LCAT) or Acyl coenzyme A: cholesterol acyltransferase

44
Q

What are lipoproteins?

A

Micelles with proteins attached.

45
Q

What types of cargo do lipoproteins carry?

A
  • Triacylglycerol
  • Cholesterol ester (cholesterol linked to fatty acid)
  • Fat soluble vitamins (A, D, E & K)
46
Q

What are the 5 distinct classes of lipoproteins and how are they named?

A

• Chylomicrons
• VLDL (Very Low Density Lipoproteins)
• IDL (Intermediate Density Lipoproteins)
• LDL (Low Density Lipoproteins)
• HDL (High Density Lipoproteins)
Classed according to density.
Each contains variable content of apolipoprotein, triglyceride, cholesterol and cholesterol ester.
The more dense they are, the higher % protein.

47
Q

Which lipoproteins are the main carriers of fat and which are the main carriers of cholesterol esters?

A

Main carriers of fat: chylomicrons and VLDL

Main carriers of cholesterol esters: IDL, LDL and HDL

48
Q

Order the lipoproteins from least dense to most dense

A

Chylomicrons, VLDL, IDL, LDL, HDL

49
Q

What are apolipoproteins and what do they do?

A

Proteins that bind to phospholipids to form lipoproteins.
• Each class of lipoprotein particle has a particular complement of associated proteins (apolipoproteins)
• Six major classes (A,B,C,D,E & H)
• apoB (VLDL,IDL & LDL) and apoAI (HDL)
• Apolipoproteins can be integral passing through phospholipid bilayer or peripheral “resting” on top
• Have two roles:
Structural:
Packaging water insoluble lipid Functional:
Co-factor for enzymes
Ligands for cell surface receptors

50
Q

What apolipoproteins are associated with which lipoproteins?

A

• apoB (VLDL,IDL & LDL) and apoAI (HDL)

51
Q

Explain how chylomicrons carry out their function.

A
  • Chylomicrons loaded in small intestine with dietary triacylglycerol, and apoB-48 added before entering lymphatic system
  • Travel to thoracic duct which empties into left subclavian vein and acquire 2 new apoproteins (apoC and apoE) once in blood.
  • apoC binds lipoprotein lipase (LPL) on adipocytes and muscle. Released fatty acids enter cells depleting chylomicron of its fat content.
  • When triglyceride reduced to ~ 20%, apoC dissociates and chylomicron becomes a chylomicron remnant
  • Chylomicron remnants return to liver. LDL receptor on hepatocytes binds apoE & chylomicron remnant taken up by receptor mediated endocytosis . Lysosomes release remaining contents for use in metabolism
52
Q

What is lipoprotein lipase?

A
  • Enzyme that hydrolyses triacylglycerol in lipoproteins
  • Requires ApoC-II as cofactor
  • Found attached to surface of endothelial cells in capillaries
53
Q

Explain how chylomicrons carry it their function using a diagram

A

Insert diagram

54
Q

Explain how VLDLs carry out their function

A
  • VLDL made in liver for purpose of transporting triacylglycerol (TAG) to other tissues.
  • Apolipoprotein apoB100 added during formation and apoC and apoE added from HDL particles in blood.
  • VLDL binds to lipoprotein lipase (LPL) on endothelial cells in muscle and adipose and starts to become depleted of triacylglycerol
  • In muscle the released fatty acids are taken up and used for energy production
  • In adipose the fatty acids are used for re-synthesis of triacylglycerol and stored as fat.
55
Q

How are IDLs and LDLs formed?

A

Formation
• VLDL deplete to form IDL and then the IDL deplete to form LDL.
• As triacylglycerol content of VLDL particles drops some,
VLDL particles dissociates from the LPL enzyme complex and return to liver
• If VLDL content depletes to ~30%, the particle becomes a short-lived IDL particle.
• IDL particles can also be taken up by liver or rebind to LPL enzyme to further deplete in TAG content
• Upon depletion to ~ 10%, IDL loses apoC & apoE and becomes an LDL particle (high cholesterol content)

56
Q

What is the function of IDL and LDL?

A

• Primary function of LDL is to provide cholesterol from liver to peripheral tissues.
• Peripheral cells express LDL receptor and take up LDL via
process of receptor mediated endocytosis
• Importantly, LDL do not have apoC or apoE so are not efficiently cleared by liver (Liver LDL-Receptor has a high affinity for apoE).

57
Q

What is the clinical relevance of of IDL and LDL levels?

A
  • Half life of LDL in blood is much longer than VLDL or IDL making LDL more susceptible to oxidative damage
  • Oxidised LDL taken up by macrophages that can transform to foam cells and contribute to formation of atherosclerotic plaques
58
Q

Using a diagram explain the process of how VLDL, IDL and LDL are used in the body

A

Insert cycle

59
Q

How do LDLs enter cells?

A

LDL enters cells by receptor mediated endocytosis
• Cells requiring cholesterol express LDL receptors on plasma membrane
• apoB-100 on LDL acts as a ligand for these receptors
• Receptor/LDL complex taken into cell by endocytosis into endosomes
• Fuse with lysosomes for digestion to release cholesterol and fatty acids
• LDL –Receptor expression controlled by cholesterol concentration in cell.

60
Q

How are HDLs synthesised?

A
  • Nascent HDL synthesised by liver and intestine (low TAG levels) • HDL particles can also “bud off” from chylomicrons and VLDL as they are digested by LPL
  • Free apoA-I can also acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form nascent-like HDL
61
Q

How do HDLs mature

A

Maturation
• Nascent HDL accumulate phospholipids and cholesterol from cells lining blood vessels
• Hollow core progressively fills and particle takes on more globular shape
• Transfer of lipids to HDL does not require enzyme activity

62
Q

What type of transport do HDLs take part in?

A

Reverse cholesterol transport
• HDL have ability to remove cholesterol from cholesterol laden cells and return it to liver
• Important process for blood vessels as it reduces likelihood of foam cell and atherosclerotic plaque formation
• ABCA1 protein within cell facilitates transfer of cholesterol to HDL. Cholesterol then converted to cholesterol ester by Lecithin Cholesterol Acyltransferase (LCAT )

63
Q

What is the fate of mature LDLs?

A

Fate of mature HDL
• Mature HDL taken up by liver via specific receptors
• Cells requiring additional cholesterol (e.g. for steroid hormone synthesis) can also utilise scavenger receptor (SR-B1) to obtain cholesterol from HDL
• HDL can also exchange cholesterol ester for TAG with VLDL via action of cholesterol exchange transfer protein (CETP)

64
Q

How can cells needing additional cholesterol obtain it from HDLs?

A

Cells requiring additional cholesterol (e.g. for steroid hormone synthesis) can also utilise scavenger receptor (SR-B1) to obtain cholesterol from HDL

65
Q

How can HDLs exchange cholesterol ester?

A

HDL can also exchange cholesterol ester for TAG with VLDL via action of cholesterol exchange transfer protein (CETP)

66
Q

Using a diagram explain how HDL carries out its function

A

Insert diagram

67
Q

What is the difference between the contents carried by chylomicrons and VLDL?

A

Chylomicrons transport dietary triacylglycerol whereas VLDLs carry triacylglycerol synthesised in the liver.

68
Q

Give a short summary of lipoprotein functions.

A

Insert table

69
Q

What is hyperlipoproteinaemia?

A

Raised plasma level of one or more lipoprotein classes.
Caused by either:
1. Over-production
2. Under-removal
There are 6 main classes of hyperlipoproteinaemias are either defects in the enzymes, receptors and/or apoproteins

70
Q

What are the 6 types of hyperlipoproteinaemias?

A

Insert table

71
Q

What is hypercholesterolaemia and what are its clinical signs?

A

• High level of cholesterol in blood
•Cholesterol depositions in various areas of body
• Xanthelasma - Yellow patches
on eyelids
• Tendon Xanthoma - Nodules on
tendon
• Corneal arcus - obvious white circle around eye. Common in older people but if present in young could be a sign of hypercholesterolaemia

72
Q

How is raised serum LDL associated with atherosclerosis?

A

Insert diagram

73
Q

How are hyperlipoproteinaemias treated?

A

First approach:
Diet: reduce cholesterol and saturated lipids in diet and increase fibre intake.
Lifestyle: Increase exercise and stop smoking to reduce cardiovascular disease.

If no response then turn too drugs:
Statins: Reduce cholesterol synthesis by inhibiting HMG-CoA reductase e.g atorvastatin.
Bile salt sequestrants: They bind bile salts in the GI tract. This forces the liver to produce more bile acids using more cholesterol e.g colestipol

74
Q

How do statins work?

A

Insert diagram

75
Q

What are the ideal cholesterol test levels (not just total cholesterol)

A

• Total Cholesterol (TC)
Ideally 5 mmol/L or less
• Non HDL-Cholesterol (total cholesterol minus HDL-cholesterol)
Ideally 4mmol/L or less
• LDL-Cholesterol (LDL-C)
Ideally 3 mmol/L or less
• HDL-Cholesterol (HDL-C)
Ideally over 1mmol/L (men) and over 1.2mmol/L (women).
• Total cholesterol:HDL-C ratio
Ratio above 6 considered high risk - the lower the ratio the better.
• Triglyceride (TG) Ideally < 2mmol/L in fasted sample

76
Q

When are chylomicrons normally present?

A

4-6 hours after a meal

77
Q

When separated what appearance to chylomicrons have?

A

Creamy appearance

78
Q

How does the intake of fibre reduce cholesterol?

A

It sequesters bile salts. These bile salts need to be replaced and cholesterol is used to make them hence removing the cholesterol.

MEH (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions