regulation of metabolism

Question 1

To coordinate metabolic processes its vital some enzymes or subject to strict controls. Name factors involved in regulation of biochemical pathways.

Answer 1

Concentrations of substrates & products. Modifications. Endocrine signals. Other enzymes.

Question 2

What did michealis & menten propose?

Answer 2

That the enzyme reversibly combines with its substrate to form an enzyme substrate complex that breaks down to product & regenerating free enzyme.

Question 3

The michealis-menten equation describes how reaction velocity varies with substrate concentration, what is this equation?

Answer 3

Vo=Vmax(s)/Km+(s)
Vo = initial reaction velocity
Vmax= maximal velocity
Km = michealis constant
(s)= substrate concentration.

Question 4

Explain a similarity in Km and (S).

Answer 4

Km & (S) are numerically equal at which the reaction velocity is at 1/2Vmax.

Question 5

Km doesn’t vary with the concentration of enzyme. Small Km (numerically) reflects a high affinity of the enzyme for substrate as low concentration of substrate is needed to half-saturate the enzyme aka to reach 1/2Vmax. These enzymes are targeted for regulation. Explain High Km.

Answer 5

A numerically high km reflects a low affinity of the enzyme for substrate as a high concentration is required to half saturate enzyme eg. to reach 1/2Vmax.

Question 6

when (S) is much greater than Km, velocity is constant & equal to Vmax. Rate of reaction is independent of (s) and is said to be ‘zero order’ with respect to substrate concentration. Explain if (s) is much less than Km.

Answer 6

Velocity of reaction is proportional to (s).The rate is said to be ‘first order’ with respect to substrate.

Question 7

what do effectors do?

Answer 7

They are molecules that bind non-covalently to an enzyme & inhibit its activity.

Question 8

What are the 2 types of effectors & explain them.

Answer 8

‘Homotropic’, usually positive, when the substrate is an effector. ‘Heterotrophic’, when effector is not the substrate, may have stimulartory or inhibitory effect.

Question 9

Processes of glycogen synthesis & glycogen breakdown are both regulated in what ways?

Answer 9

Allosterically, covalently and by induction/repression of synthesis.

Question 10

Name the enzyme for glycogen synthesis.

Answer 10

Glycogen synthase.

Question 11

Name the enzyme for glycogen breakdown.

Answer 11

Glycogen phosphorylase.

Question 12

What process is the fed state, and which the fasted?

Answer 12

Fed state = glycogen synthesis (glucose to glycogen)
fasted state = Glycogen breakdown (Glycogen to glucose)

Question 13

What molecule activates glycogen synthase and inhibits glycogen phosphorylase?

Answer 13

glucose 6-phosphate.

Question 14

Adenosine monophosphate (AMP) has no effect on ___ but allosterically activates ___. Important in exercising ___ muscle

Answer 14

glycogen synthase, glycogen phosphorylase. Skeletal.

Question 15

ATP allosterically inhibits ___, but has no effect on ___

Answer 15

glycogen phosphorylase, glycogen synthase.

Question 16

AMP & ATP both don’t have an effect on what enzyme?

Answer 16

glycogen synthase.

Question 17

If fed, more glucose does not need to be made by glycogen breakdown….

Answer 17

so glucose allosterically inhibits glycogen phosphorylase, with no effect on glycogen synthase. This is important in liver.

Question 18

What does Allosteric mean?

Answer 18

Happens In the cell. Involves binding of an effector molecule to the enzyme, altering its activity.

Question 19

There are 6 components of hormone action to consider before looking at glycogen synthase and phosphorylase.

Answer 19

Signal, receptor, coupling, amplification, effect, termination.

Question 20

In terms of the signal; what are the 3 categories of hormones?

Answer 20

1) Peptide or polypeptides e.g glucagon & insulin.
2) steroid hormones e.g. glucocorticoids, sex steroid hormones.
3) Amino acid derivatives. e.g T3, T4 Catecholamines (e.g-adrenaline)

Question 21

Hormones must bind to receptors in first step for metabolic processes. Where do the hormones bind to receptors?

Answer 21

Steriods; intracellular receptors interact with chromatin and effect mRNA transcription.
Others; bind to receptors on surface of plasma membrane.

Question 22

Extracellular receptors are usually glycoproteins.

Answer 22

N-linked region contains oligosaccharides on the extracellular surface- these convey speciality.

Question 23

peptide and amino acid hormone receptors are coupled to a specific what?

Answer 23

Guanyl-stimulatory binding protein (Gs-protein), on the intracellular surface of the plasma protein.

Question 24

Guanyl protein consists of 3 subunits, what are they?

Answer 24

a subunit (45kDa),
Beta subunit (35kDa)
y subunit (7kDa)

Question 25

When there is no hormone signal, where does the a-subunit rest?

Answer 25

In the GDP & there are no interactions between receptor & Gs-protein.

Question 26

If there is a hormone signal, what happens to subunit a?

Answer 26

It changes its conformation, loses the GDP and binds GTP. This a-GTP subunit dissociates from the Gs-protein & binds/activates enzyme ‘adenylate cyclase, located in plasma membrane.

Question 27

What happens if there is no further hormones stimulation?

Answer 27

GTP is hydrolysed to GDP, the a-GDP subunit dissociates from adenylate cyclase and re-associates with rest of the Gs-protein subunits.

Question 28

when bound to the a-GTP subunit of the Gs-protein, adenylate cyclase is activated & able to catalyse the formation of what?

Answer 28

Cyclic AMP (cAMP) from ATP. 100s molecules of cAMP are produced for every activated molecules of adenylate cyclase.

Question 29

cyclic AMP is known as what?

Answer 29

a second messenger.

Question 30

what enzyme is cAMP a potent activator of?

Answer 30

Protein kinase A.

Question 31

Describe and explain protein kinase a.

Answer 31

A tetramer, 2 regulatory subunits & 2 catalytic subunits. The catalytic subunits catalyse the phosphorylation of specific serine or threonine residues on target proteins.
The phosphorylated proteins may activate or inactivate enzymes.

Question 32

Protein kinase A can phosphorylate specific proteins that bind to promoter regions of DNA causing what?

Answer 32

Causing increased expression of specific genes.

Question 33

Termination; loss of hormone signal. Explain dephosphorylation of proteins.

Answer 33

The phosphate groups added to proteins by protein kinases are removed by the actions of ‘phosphoprotein phosphates’, enzymes that hydrolytically cleave phosphate esters. Changes in enzymatic activity induced by protein phosphorylation are not permanent.

Question 34

Explain hydrolysis of cAMP.

Answer 34

cAMP is readily hydrolysed to 5’-AMP by phosphodiesterase. 5’-AMP is not an intracellular signalling molecule. Note that phosphodiesterase is inhibited by methylxanthine derivatives such as caffeine.

Question 35

Explain inhibition of glycogen synthesis by a cAMP cascade.

Answer 35

Glycogen synthase a (NOT phosphorylated & most active form) is converted to b form (Is phosphorylated and inactive) by phosphorylations at a number of sites on the enzyme.

Question 36

Binding of glucagon or adrenaline to hepatocyte/ muscle cell receptors results in activation of what?

Answer 36

Adenylate cyclase.

Question 37

cAMP is synthesised which activates protein kinase A. Protein kinase a phosphorylates glycogen synthase a to b therefore inactivates glycogen synthesis.

Answer 37

Glycogen synthase B can be transformed back to glycogen synthase a by phosphoprotein phosphatase type 1, which removes the phosphate group hydrolytically.

Question 38

the binding of glucagon or adrenaline to receptors signals the need for what?

Answer 38

For glycogen to be degraded- either to elevate blood glucose levels or to provide energy in exercising muscles.

Question 39

protein kinase a phosphorylates the inactive form of what resulting in its activation.

Answer 39

In phosphorylase kinase.

Question 40

Active phosphorylase kinase phosphorylates glycogen phosphorylase b to a which begins what?

Answer 40

Glycogen breakdown.

Question 41

cAMP levels decrease when?

Answer 41

when in the presence of insulin.