8. gluconeogenesis

Question 1

what is gluconeogenesis

Answer 1

synthesis of glucose from no-carbohydrate precursors

lactate, amino acids, glycerol

Question 2

which organs utilise gluconeogenesis?

Answer 2

brain (fatty acids transported on albumin cannot cross BBB), RBC, kidney medula, lens and cornea of eye

need a continuous supply of glucose

Question 3

why doesn’t gluceoneogenesis occur by the reversal of glycolysis?

Answer 3

overall equilibrium favours pyruvate formation as delta G<0

Question 4

conditions where gluconeogensis occur

Answer 4

1. after exercise: lactate is toxic to muscle, resynth to glucose in liver by cori cycle
2. short term fasting: depleted glycogen stores

liver glycogen depleted within 24h- synth of glucose from alanine

3. trauma: peripheral insulin resistance in hypermetabolic phase of response to injury- tissues feel starved of glucose
4. uncontrolled diabetes mellitus: insensivity to insulin/ lack, tissues feel starved of glucose despite hyperglycaemia

Question 5

in which tissues does gluconeogenesis occur?

Answer 5

liver, kidney, small intestine (some ability)

Question 6

how long can the glucose in glycogen last?

Answer 6

1 day

Question 7

where does gluconeogensis occur in the cell?

Answer 7

• Pyruvate carboxylase located in mitochondrion
• All other reactions occurs in cytosol

Question 8

difference of glycolysis and gluconeogenesis

Answer 8

•Reversal of glycolysis except for 3 steps. Different proteins and enzymes occurring

–1. Pyruvate to PEP

–2. F1,6BP to F6P

–3. G6P to glucose

Question 9

1. what happens to pyruvate?

Answer 9

form oxaloacetate-> PEP

Pyruvate(mito) + CO2 + ATP oxaloacetate(mito) + ADP +Pi

pryruvate carboxylase is the enzyme in mitochondria

oxaoloacete is then transported to cytosol

Question 10

transport of oxaloacetate to cytosol

Answer 10

Question 11

2. reaction of oxaloacetate in cytosol

Answer 11

oxaloacetate(cyto) + GTP -> PEP(cyto) + GDP + CO2

PEP carboxykinase enzyme

Question 12

in which tissues is pyruvate carboxylase found?

Answer 12

all tissues

Question 13

F1,6BP to F6P reaction

Answer 13

Fructose 1,6-bisphosphate + H2O -> Fructose 6-phosphate +Pi

enzyme: Fructose 1,6-bisphosphatase

Question 14

G6P to glucose

Answer 14

G6P + H20-> glucose + Pi

enzyme: glucose-6- phosphatase

Question 15

Stoichiometry of gluconeogenesis

Answer 15

Question 16

Answer 16

Question 17

hormonal regulation of gluconeogensis

Answer 17

Insulin -promotes synthesis of glycolytic enzymes PFK, PK, PFK2.

–Inhibit synthesis of PEPCK – important in diabetes

Glucagon

–increases expression of PEPCK, F1,6BPase.

Question 18

the Cori cycle

Answer 18

Question 19

Amino acids as gluconeogenic precursors

Answer 19

• Remove amino group
• Carbon skeletons can be converted to glucose.

Question 20

glycerol

Answer 20

• Breakdown of adipose tissue
• Triacylglycerol converted to FFA and glycerol.
• Glycerol used as gluconeogenic substrate

FFA cannot form glucose

Question 21

effects of alcohol on gluconeogenesis

Answer 21

metabolism of ethanol increases the conc of NADH, intermediate reactions diverted to alternative reaction pathways

Question 22

Answer 22