Systems to cells Flashcards
How much ATP does every human body have?
100-250g
How much ATP does an individual need?
50-75kg (body weight)
How much ATP is reformed everyday?
1000x
Where is energy stored in ATP and how is it released ?
the last phosphate group of ATP, released by hydrolysis of the high energy gamma phosphate bond
Why is glucose a great storage molecule?
It can be complexly oxidised and stored as glycogen
Where is glucose converted to glycogen at?
liver
What is the main stages in ATP production from glucose?
- glycolysis - glucose become pyruvate releasing 2ATP// 2. pyruvate is converted inti Acetyl-CoA in aerobic conditions // 3. Krebs cycle produces 6NADH and 2FADH and 2ATP // FADH and NADH produce 2 ATP EACH
Give examples of some biosynthetic reactions
production of amino acid/ lipid membrane/ RNA/ nucelotides…
In anaerobic conditions what is produced by glycolysis?
lactate
What is glucose stored at when in excess?
triglycerides(in adipose tissue) and glycogen
What happens when glucose levels are low?
Muscles become exporters of glucose and fatty acids
What happens when blood sugar is hight
?
INSULIN is released// glucose is then uptake from the blood, glycogen is produced (converted in the liver) and triglycerides are formed (stored in adipose tissue)
What occurs at low blood sugar?
GLUCAGON is released, glycogen break down occurs, increasing glucose levels
What releases insulin and glucagon?
insulin = pancreatic beta-cells // glucagon = pancreatic alpha-cells
What is gluconeogenesis ?
metabolic pathway generating glucose form pyruvate /lactate (non-carbohydrate substrates)
What stimulates gluconeogenic ?
insulin
What inhibits gluconeogenic ?
glucagon
Where is glycogen stored in cells?
close to mitochondria allowing it to be easily accessed for energy conversion in muscle fibbers
What is the fed state? What does it do?
high blood glucose levels , triggers release of insulin
What is the fasted state? what does it do?
low blood glucose levels , triggers release of glucagon
Describe the enzyme pathway of converting glucose to glycogen.
hexokinase-> phosphoglucomutase-> glycogen synthase
Describe the enzyme pathway of converting glycogen to glucose.
Glycogen phosphorylase-> phosphoglucomutase -> glucose - 6- phosphate
What is the intermediate in the conversion of glucose to glycogen ?
glucose 6 phosphate
What does hexokinase do?
Adds a phosphate to carbon 6 of glucose allowing it to later become glycogen
What is the role of phosphoglucomutases?
changes the position of phosphate group from carbon 6 to carbon 1 or vies versa
What is the regulated reciprocal in the enzyme pathway converting glucose to glycogen ?
glycogen phosphorylase and glycogen synthase// different enzyme is used for different directions of the reaction
What enzymes are involved in phosphorylation?
kinase - adds phosphate to either serine/threonine residual or tyrosine residual /// phosphatase removes phosphate
What mechanisms regulate enzymes
1.change in activity/ 2. change in location/ 3. change in rate of biosynthesis
What changes occur during : prenylation/ ubiquitination/ glyconanation?
adding lipid group/ protein group/ carbohydrate group
Explain the process of phosphorylation.
Addition of a phosphate from an ATP using kinase, salt bridge forms between -ve phosphate and positive aguine and lysine residuals changing the shape
What is the impact of insulin on glucose 1-phsophate?
Switches on glycogen synthase which converts glucose 1 phosphate into glycogen
What is the impact of glucagon on glycogen?
Glucagon switches on glycogen phosphorylase which in turn converts glycogen to glucose 1 phosphate
What is the effect of insulin on glucose phosphate 1? What does this result in?
glucose phosphate 1 turns on glycogen synthase and turns off glycogen phosphorylase- PROMOTING CONVERSION TO GLYCOGEN
What is the effect of glucagon on protein kinase A? And what does this result in?
protein kinase turns glycogen synthase off and glycogen phosphorylase on- PROMOTING CONVERSION TO GLYCOGEN
What are insulin and glucagon?
polypeptide hormones which are released from the pancreas and bind to specific receptors on muscles/ fat and liver cells
What is meant by irreversible and reversible steps?
irreversible steps - require different enzymes for different directions of reaction// reversible steps use the same enzyme for both direction of reaction
What is the rate determining step in a reaction?
The slowest step , which determines the speed of the overall reaction
Give an example of allosteric modulation
Phosphorylation, the -ve phosphate charge attracts the positive amino acid of arguine and lysine changing structure.
Define diabetes
the dysregulation of glucose homeostasis resulting in high blood sugar (glucose cannot be converted by glycogen in the liver and therefore there is lots of glucose in the blood)
What causes type 1 diabetes ?
Genetics cause/ born with an autoimmune disease, therefore breaks down beta cells
What causes type 2 diabetes ?
due to lifestyle / increased glucose levels, overwhelming the insulin therefore the beta cells don’t react to signals preventing glucose to be converted to glycogen in the liver therefore increasing glucose in the blood
What is the role of leptin gene in mice?
Leptin provides signals to make an individual feel full
What does a lack of leptin cause?
hyperphagia (huger) causing increased feeding leading to obesity and hyperglycaemia ( increased glucose levels in blood)
What is the role of the Akt gene?
Manage glucose stores and maintain glucose homeostasis// used by brown bears during hibernation to prevent obesity and diabetes
What models were used to understand cures for humans with diabetes ?
mice (leptin mutations)// brown bears (Akt gene) // Humming bird (high blood sugar diet prior to migration)
What is prepoinsulin?
A complex polypeptide which can be modified to become insulin. consist of chain A, chain B and C-peptide
What is the role of the ER for newly synthesized insulin?
to fold and oxidate it
Briefly outline translation of preproinsulin
- mRNA detected by ribosome/2. specific signal sequence pauses translation by SRP/ 3. soluble protein is added/ 4. signal sequence peptiase cuts the protein/ 5. synthesised insulin peptide moves into ER - where it becomes folded and oxidised
What is meant by membrane trafficking?
process which moves things around the cell, GEORGE PALADE(scientist involved) .
Describe the movement of proinsulin through the cell
ER-> golgi -> vesicles -> cell membrane -> released from cell
What happens to proinsulin within the ER?
Pre-sequenced is cleaved by signal peptidase, chain A and chain B are separated and disulphide bonds form
What is the final stage of processing of proinsulin?
in secretory vesicles enzyme pro hormone convertase (PC1/3 and PC2) convert proinsulin into insulin via the removal of C peptide
Why is membrane trafficking specific and selective?
Nature of the membrane only allows certian moleules to pass through// diferent processess are tailored towards allowing certian molecules into the cell
Summarise the conversion of proinsulin to insulin . (LOCATION - PROCESS)
ER- folding and formation of disulphide bonds// GOLGI - packaged into vesicles// VESSICLES - c-peptide is removed and chain A and B are split forming insulin// Insulin is released increasing blood glucose levels.
Why are membrane trafficking specific and selective ?
membrane proteins are specific // compartomalization separates stages of processes
How is insulin released from the cell?
- increased blood sugar 2. GLUT2 opens , glucose the moves into beta -cells 3.glycolysis is triggered (more ATP is produced) 4. due to increased ATP k+ channel closes (creates depolarisation) 5. opens CA2+ voltage gate, Ca2+ enters the cell 6. CA2+ binds the vesicles contain insulin 7. insulin is released via exocytosis
What triggers the release of insulin from secretary vesicles?
Calcium binds to protein complexes on the cell membrane, causing vesicles to fuse with cell membrane and release Ca2+
Give examples of a transport protein which uses a chemical gradient.
GLUT2 // GLUT4
What controls metabolism of glucose within beta-cells?
The glucose concentrations inside and outside the cells
Give examples of a transport channel which uses an electrical gradient
Ca 2+ voltage channel
Does GLUT2 have a high or low affinity to glucose/ what does this mean?
Low affinity meaning high levels of glucose is needed for GLUT2 to open and allow glucose molecules to move into the cell
What does the Michaelis Menten curve show ?
For catalysed enzyme reactions velocity increases rapidly then reaches a plateau. (plateau is found at high concentrations of substrates)
How to calculate enzyme concentration using the Michaelis Menten equation?
Km (concentration )= 0.5 Vmax (speed of enzyme// explains the concentration which causes an enzyme to work at half of the max velocity.
How to calculate Vmax using the Michaelis Menten equation?
Vmax= 2km
What do islets contain in the liver?
alpha cells / beta cells and delta cells
How do islets release insulin?
In waves after signalling to other islets through hormonal and neural connections
What does a enzyme with a HIGH affinity need in terms of Km of substrate concentration?
high affinity = low Km
What does a enzyme with a LOW affinity need in terms of Km of substrate concentration?
LOW affinity= high Km (Enzyme substrate complexes are less likely to form therefore more substrates are needed to ensure reaction occurs)
Name some insulin receptors.
GLUT2 AND GLUT4
What is glucose transport in fat an muscle cells controlled by.
membrane trafficking e.g. regulated exocytosis triggered by insulin
What is the structure of an insulin receptor?
Alpha 2 Beta 2 polypeptide, held together by disulphide bonds
What is biosynthesis and degregation ?
Biosynthesis = process converting simple compounds into other compounds
// degradation = breakdown processes releasing molecules often later used in biosynthesise
How is insulin produced/ processed?
- transcription + translation forms preproinsulin// 2. Preproinsulin –> proinsulin through cleavage of a single peptide of preproinsulin// 3. Within ER proinsulin –> mature insulin through cleaving C-peptide and separating A and B chains
Why is personalised medicine beneficial ?
specific to an induvial therefore more effective/ certain drugs have negative affects on individuals- this reduces these issues
How has technology altered how we sequence genomes?
Now much faster // refer to human genome / genome maps// can find conditions across different levels (DNA and RNA)
What is an X-linked condition?
phenotype which is determined by a genotype located on the x chromosome // more frequent in females
What are STRs ?
Short tandem repeats , sections of DNA which are repeated consecutively- everyone has these but the location and number of repeats differ
What is the function of the inappropriate aggression gene?
metabolise excess neurotransmitters which effectively calm the flight or fight response
What are the two enzymes related to the inappropriate aggression gene?
MOXA and MOXB (they have identical intron and Extron structure
What is a truncated gene?
A gene which has an early stop codon resulting in a shorter protein
What is the influence of a mutation of MOXA ?
reduced enzyme activity therefore there is no control of the neurotransmitters and the individuals becomes more aggressive
Give some examples of behaviours associated with a mutant MOXA gene
restlessness/ attention deficit/ bite wounds/ readily attacks….
What is heritability?
measurment of how well differences in peoples genes account for differences in their traits
How much DNA do monozygotic twins and dizygotic twins share ?
monozygotic = identical twins = 100%// dizygotic = non-identical twins= 50%- the same as siblings
What are single nucleotide polymorphism?
Change in single base pair, this is the main source of genetic variations.
What is the aim of the GWAS (GENOME WIDE ASSOCIATION)
to help scientist identify genes associated with a particular disease/ trait
How does exercise help type 1 and type 2 diabetes?
Increases insulin sensitivity (impacting T1D) as glucose is removed from blood easier// increased GLUT4 activity (impacts T1D and T2D ) - increases transportation of glucose// increases glycaemic control
How is energy balance important in developing type 2 diabetes?
helping to maintain blood glucose homeostasis
Give an example of insulin modulating gene expression.
insulin sends signals through IRS1, activating LxR expressing SREBP1 turning on fat storage
Where are GLUT 4 and GLUT2 membrane transporters located?
GLUT2= beta pancreatic cells // GLUT4 = fat and muscle cells
Outline some effects phosphorylation has on proteins
Change in activity/ stability and location
What is a difference between GLUT 2 and GLUT 4
GLUT 2 = high affinity // GLUT4= low affinity
