[FMS] NAM - liver and gluconeogenesis

Question 1

What is the physiological circulating and average fasting glucose concentration?

Answer 1

• Physiological circulating glc concentration:
  3.9-6.2 mM
• Average fasting:
  4.4-5 mM for most adults

If it drops to 2.5 or less coma and death can result

Question 2

What are the 3 advantages of glucose as a metabolic fuel?

Answer 2

• Water soluble , so does NOT require a carrier in the circulation
• Can cross the blood-brain barrier
• Can be oxidised anaerobically

Question 3

What are the disadvantages of glucose as a metabolic fuel?

Answer 3

• Relatively low yield of ATP/mole compared to fatty acids
• Osmotically active
• In high concentrations can directly damage cells or lead to accumulation of toxic by-products (fructose, sorbitol)

Question 4

why is glucose an important metabolic fuel

Answer 4

source of NADP
source of pentose sugar
source of carbon
water soluble, crosses BBB, oxidised anaerobically

Question 5

why does gluconeogenesis occur

Answer 5

in LOW carbohydrate conditions glucose is synthesised from non-carbohydrate sources such as:
Lactate
glycerol
other monosaccharides
glucogenic amino acids (all except leu, lys)
NOT FROM FATTY ACIDS

Question 6

What is gluconeogenesis

Answer 6

reverse of glycolysis but includes 3 irreversible reactions in glycolysis that needs to be bypassed in order for gluconeogenesis to occur

Question 7

outline the steps of glycolysis and gluconeogenesis including any enzymes involved

Answer 7

Question 8

what are the 3 irreversible reactions in glycolysis that need to be bypassed in glyconeogenesis?

Answer 8

ie 1st, 3rd, last

Question 9

What do the blood glucose, insulin and glucagon levels in a normal person over 24 hours of normal eating behaviour look like?

Answer 9

INSULIN + GLUCOSE INCREASE

GLUCAGON STAYS SAME!!

Question 10

what are the 3 sources of blood glucose

Answer 10

• Diet
• Liver glycogen
• Liver gluconeogenesis

Question 11

where does gluconeogenesis and glycolysis occur

Answer 11

in cytosol

Question 12

outline the reaction between PEP and Pyruvate

Answer 12

Question 13

in what 2 ways is gluconeogenesis regulated?

Answer 13

1) Mobilisation of substrate through:
- glycerol from fat breakdown
- amino acids from muscle protein breakdown

2) activation of enzymes, such as:
- glucose-6 phosphotase, fructo-1.6- bisphosphatase, pyruvate carvoxylase, and PEP carboxykinase (the enzymes needed in gluconeogenesis)

Question 14

what 2 cells are the islets of langerhans in the pancreas made up of, and what do they secrete?

Answer 14

• Beta cells secrete insulin
• Alpha cells secrete glucagon

remember -glucagon’ has an A in it, so its alpha, insulin doesnt have an A so by default is Beta

Question 15

what is the difference between insulin and glucagon

Answer 15

insulin is an anabolic hormone. It promotes synthesis and storage

glucagon is a catabolic hormone. It promotes degradation of stored fuel

Question 16

how does insulin maintain blood glucose in the liver

Answer 16

Inhibition of gluconeogenesis

activation of glycogen synthesis (glycogen synthase activated)

Increased Fatty Acid synthesis and lipid assembly

Increased aa uptake and protein synthesis

Question 17

how does insulin maintain blood glucose in the muscles

Answer 17

Increased glucose uptake by increasing glucose transporters (GLUT4)

Increased aa uptake and protein synthesis

activation of glycogen synthesis (glycogen synthase activated)

Question 18

how does glucagon maintain blood glucose

Answer 18

increase in blood glucose
↑ glycogenolysis and gluconeogenesis (liver).

Increase in circulating fatty acids and ketone bodies
↑ adipose tissue lipolysis, ↑fatty acid oxidation in the liver and ketone body formation.

. Decrease in plasma amino acids
↑uptake by the liver for gluconeogenesis.

Question 19

What is the role of glucose in skeletal muscle?

Answer 19

Question 20

What is the role of glucose in the heart/liver?

Answer 20

Question 21

Why does the adipose tissue need to do glycolysis?

Answer 21

• The adipose tissue needs to do glycolysis because when the fat gets transferred to the adipose tissue for storage, you can’t get triaglyceroles entering the membrane
• You have to hydrolyse them in the circulation and then the fatty acids get into the adipose cell.
• You make triacylglycerol by sticking them on glycerol phosphate.
• The liver have glycerol kinase but the adipose cell does not so the only way to resynthesise the triacylglycerol is to go halfway down glycolysis, make glyceraldehyde-3-phosphate, reduce this to glycerol phosphate and you can stick the fatty acids onto it and store it.

Question 22

what do erythrocytes need to maintain integrity of the erythrocyte membrane

Answer 22

NADPH

Question 23

what pathway provides NADPH for metabolising glucose.

Answer 23

pentose pathway shunt AKA hexose monophosphate shunt (they can be used interchangably)

Question 24

what is the function of G6PDH

Answer 24

glucose-6-phosphate dehydrogenase (G6PDH).

removes hydrogen from glucose

Question 25

what is the most commonest human enzyme deficiency

Answer 25

G6PD (Glucose-6-phosphate dehydrogenase)  deficiency is the commonest human enzyme deficiency.

Question 26

what kind of disorder is G6PD and what sex is affected

Answer 26

X-linked hereditary disorder asymptomatic patients are predominantly male.

Question 27

What are the triggers for haemolytic anaemia in people with G6PD deficiency

Answer 27

favism Favism results from the ingestion of fava beans.

Question 28

describe what happens after ingesting 100g of glucose over a few hours, and a few days

Answer 28

after ingesting glucose, glycogen is high after a few HOURS gluconeogenesis increases over a few DAYS

Question 29

what is the difference between cori cycle and glucose-alanine cycle

Answer 29

while **both cycles involve the transport of metabolites (lactate or alanine) from muscle cells to the liver for gluconeogenesis,** the key distinction lies in the specific metabolite produced in muscle cells: **lactate in the Cori cycle** and **alanine in the Glucose-Alanine cycle.**

Question 30

compare the liver in its fed and fasting state.

Answer 30

Question 31

compare the muscle in its fed state and aerobic conditions.

Answer 31

Question 32

compare the brains pathway in its fed and fasting state.

Answer 32

Question 33

compare the erythrocytes pathway in its fed and fasting state.

Answer 33

Question 34

Describe the glucose tolerance curves of normal and diabetic subjects (type 1 and 2)

Answer 34

type 1 goes above renal threshold, so you will see it in urine normal and type 2 is below renal threshold so you will not see it in urine