Week 6

Question 0

What does pyruvate dehydrogenase require as a cofactor?

Answer 0

PDH requires thiamine pyro phosphate as a co factor.

Question 1

What is the link reaction?

Answer 1

Pyruvate to acetyl CoA through pyruvate dehydrogenase.

Question 2

What is thiamine pyro phosphate ?

Answer 2

A lack of thiamine disrupts pyruvate dehydrogenase and causes Beri Beri or Wernicke-Korsakoff Syndrome in alcohol addicts.

Thiamine pyrophosphate is an irreversible step and commits the carbon chain to energy production or lipid synthesis.

Question 3

How is thiamine pyrophosohate activated and inactivated?

Answer 3

Thiamine pyrophosphate is activated by Ca2+ and inactivated by high ratios of coenzyme A, NADH:NAD, and ATP:ADP.

Question 4

What are the main outputs of the Krebs cycle?

Answer 4

The main outputs of Krebs are FADH, NADH2, Co2 and GDP.

Question 5

What enzymes is the Krebs cycle controlled by?

Answer 5

Krebs is controlled by citrate synthase, isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase.

Question 6

What is oxidative phosphorylation?

Answer 6

It is a 2 coupled process to synthesise ATP.
NADH/FADH are used to create a proton gradient (oxidation).
The energy from the protein gradient is then used to drive phosphorylation (ADP to ATP)

Question 7

What is the electron transport chain?

Answer 7

A way to generate a proton gradient to generate energy to perfume ATP synthesis

Question 8

Where does NADH bind on the transport chain and which complexes does it pass through?

Answer 8

NADH binds at complex 1 with a total of 6H+ transported using energy from electrons generating a large protein gradient across the well insulated inner membrane of mitochondria.

NADH passes though complex 1, 3 and 4.

Question 9

Where does FADH2 bind?

Answer 9

FADH2 binds at complex 2, and causes 4 H+ to be transported.

Question 10

There is an antiporter in the inner mitochondrial membrane to allow the transport of ATP? What does it do?

Answer 10

ADP is transported into the mitochondria to supply the ATPase, ATP is transported out. Antiporter in inner mitochondrial membrane allows this.

Question 11

How many protons are required to cross the membrane to synthesise a molecule of ATP?

Answer 11

4 protons must pass into the matrix along with phosphate coursing the inner membrane to produce 1 ATP.

Question 12

Can NADH produced in the cytosol be reoxidised by electron transport?

Answer 12

No it has to be transported back to the matrix through a series of reactions to be reoxidised.

Question 13

Where are beta cells in the islets of langerhans found?

Answer 13

The beta cells are mostly central and most abundant. They secrete insulin.

Question 14

Where are the alpha cells in the islets of langerhans found?

Answer 14

Alpha cells are found at the periphery secreting glucagon.

Question 15

What does ATP do to the Katp channels during insulin secretion?

Answer 15

ATP closes Katp channels, depolarising the membrane.

Question 16

What induces the exocytosis of insulin?

Answer 16

Ca2+ influx and CICR induce the exocytosis of insulin.

Question 17

What does the autonomic nervous system do to insulin secretion?

Answer 17

The PNS drives insulin secretion whilst the sympathetic system inhibits insulin secretion.

Question 18

What is the significance of C peptide in a clinical situation?

Answer 18

A free C peptide is made during insulin procession in the Golgi. C peptide is a useful marker of endogenous insulin production.

Question 19

What are the effects of insulin on the liver?

Answer 19

Insulin increases glycogen storage and VLDL production but gluconeogensis and ketone body production are inhibited.

No glut 4 in the liver

Question 20

What are the effects of insulin in muscle?

Answer 20

Glut4 inserted and favours the use of glucose.

Glycogen, triglyceride and protein synthesis increase.

Question 21

What does exercise do to the muscle in terms of insulin?

Answer 21

Exercise Via adrenalin induces glut4 and synergises with insulin.

Question 22

What is the effect of insulin on fat?

Answer 22

Glut 4 inserted and favours uptake of glucose. Triglyceride storage increased and export of free fatty acids and glycerol reduced.

LDL exported to endothelium where it extracts fatty acids from VLDL.

Question 23

What the effects of glucagon on the liver?

Answer 23

Glucagon receptor is a GPCR linked to Gs.

Glycogen breakdown and gluconeogenesis increase.

Fatty acids used as an energy source and for ketone body production

Question 24

What is the effect of glucagon on fat and muscle?

Answer 24

At high levels glucagon causes lipolysis in adipocytes and proteolysis in muscles.

However glucagon largely cleared by liver. (First pass metabolism). So main effect on liver.

Question 25

What does somatostatin do?

Answer 25

Somatostatin is a peptide hormone released from D cells of stomach, duodenum and pancreas.

It’s released is stimulated by H+ and inhibited by ACh. Acts on G cells to inhibit release of Gastrin, CCK and secretin. (And insulin and glucagon if can get to cells).

Question 26

Is growth hormone secreted more during the day or at night?

Answer 26

Growth hormone is secreted more at night through pulsatile release.

Question 27

Which splice variants of growth hormone is more dominant?

Answer 27

22kDa form predominates

20kDa form may have fewer of the acute metabolic actions.

Question 28

How does growth hormone bind to a plasma protein?

Answer 28

About 40% of growth hormone binds to a plasma protein made by cleaving its receptor.

Question 29

What are the diabetogenic effects of GH?

Answer 29

GH acts via a tyrosine associated receptor leading to protein phosphorylation.

Relied effects on liver (gluconeogenesis), fat(increased lipolysis), muscle (decreased glucose uptake) and insulin resistance.

Question 30

What are IGFs and what do they do?

Answer 30

IGF1 is the main active one.
IGF2 not controlled by GH.

They enhance protein synthesis and growth. Can cause hypoglycaemia.

Question 31

T4 gets deiodinated to T3 by two enzymes, what are they and how are they different?

Answer 31

Type 1 which is found in liver, kidney and thyroid and inhibits by stress and caloric restriction.

Type 2 is found in pituitary, CNS and placenta. Is constitutive.

Question 32

What are the acute effects of thyroid hormone?

Answer 32

Thyroid hormone increases basal metabolic rate and heat production via mitochondrial decoupling.

Increases Gluconeogenesis and glycogenolysis in the liver.
Causes lipolysis and lipogenesis.

Question 33

What are the acute effects of glucocorticoids?

Answer 33

Glucocorticoids act via a nuclear receptor, inducing gene transcription. They inhibit insulin responses and enhance SNS responses. Targets glucose to brain.

In liver promotes gluconeogenesis and glucose releases.
In fat lipolysis. (Glycerol for glucose, free fatty acids for energy)

Question 34

What are the chronic effects of glucocorticoids?

Answer 34

Immunosuppression.
Reduction in inflammation and cytosine production.
Stimulates haematopoiesis
Fat redistribution from peripheral to central.
Skin think Thinning.