Lecture 27- glycogenesis & biosynthesis of glucose, glycogen & starch

Question 1

When is gluconeogenesis required?

Answer 1

When you can’t get glucose from your diet and your liver is depleted
Uses non-carbohydrate precursors
Occurs in liver and kidney

Question 2

Gluconeogenic precursors

Answer 2

Molecules that can be used to produce a new synthesis of glucose
Includes glycolysis intermediates, citric acid cycle intermediates, carbon skeleton of amino acids

Question 3

Precursor: glycerol

Answer 3

Released during hydrolysis of triacylglycerols
It is phosphorylated by glycerol kinase to glycerol phosphate
This is oxidised by glycerol phosphate dehydrogenase to dihydroxyacetone phosphate

Question 4

Precursor: lactate

Answer 4

Produced in exercising muscle when ATP demand exceeds supply
Transferred to the liver, converted to pyruvate, then glucose
Known as ‘The Cori Cycle’

Question 5

Futile cycle

Answer 5

Creates products only for them to be broken down

Question 6

Precursor: amino acids

Answer 6

Alanine can move from muscle to liver (it is transmitted back to pyruvate)
Called the ‘glucose alanine cycle’
Transports nitrogen from muscle to liver where it is used for urea biosynthesis

Question 7

Metabolism of some amino acids

Answer 7

α-ketoacids formed from glycogenic amino acids
Enter TCA cycle and form oxaloacetate
Others form acetyl CoA (irreversible reaction)

Question 8

Gluconeogenesis pathway

Answer 8

Occurs in mitochondria & cytosol
Seven glycolysis reactions run in reverse
3 reactions are irreversible- large -ve free energies, overcome by 4 gluconeogenic enzymes

Question 9

Pyruvate carboxylase

Answer 9

Catalyses a highly exergonic reaction
Needs a free energy input to overcome it
Needs 2 enzymes- pyruvate carboxylase & PEPCK

Question 10

Pyruvate carboxylase steps

Answer 10

1. CO₂ is activated and transferred by pyruvate carboxylase to its biotin prosthetic group
2. The enzyme then transfers the CO₂ to pyruvate, generating oxaloacetate
3. oxaloacetate cannot cross the mitochondrial membrane so it is reduced to malate that can

Question 11

PEP Carboxykinase (PEPCK)

Answer 11

Phosphoenolpyruvate carboxykinase
Monomeric enzyme (610 residues)
Catalyses the decarboxylation/phosphorylation of oxaloacetate
Located in mitochondria & cytosol in humans

Question 12

Gluconeogenesis membrane transport

Answer 12

Oxaloacetate -> malate -> oxaloacetate route favoured
Produces cytosolic NADH

Question 13

Steps of gluconeogenesis

Answer 13

1.PEP to fructose 1,6-bisphosphate
2. fructose-1,6-bisphosphate is hydrolysed
3. fructose-6-phosphate is isomerised
4. glucose-6-phosphate is hydrolysed (only present in over & kidney)

Question 14

Regulation of gluconeogenesis

Answer 14

Gluconeogenesis & glycolysis are reciprocally regulated
3 substrate cycles are good points for regulation

Question 15

Glycogen main stores

Answer 15

Skeletal muscle & liver
In muscle it serves as a fuel reserve for ATP synthesis

Question 16

Glycogen structure

Answer 16

Has one reducing end but a non-reducing end on every branch (so rapid mobilisation)

Question 17

Glycogen degradation

Answer 17

Separate cytosolic enzymes required
3 enzymes involved: glycogen phosphorylase, glycogen deb ranching enzyme, phosphoglucomutase

Question 18

Glycogen phosphorylase

Answer 18

Binds pyridoxal-5’ phosphate
Enzyme activity: allosteric interactions & covalent modification, induces conformational change

Question 19

Glycogen debranching enzyme

Answer 19

This enzyme is bifunctional with separate active sites: acts as α(1->4) transglycosylase- moves trisaccharide units to non-reducing branch end then hydrolytic ally removes the remaining glycol Ising amyloid-α(1->6)-glucosidase activity

Question 20

Phosphoglucomutase

Answer 20

Glycogen phosphorylase converts the glycosyl units of glycogen to G1P
then phosphorylation of glucose molecule followed by a re-phosphorylatioon of the enzyme
G6P continues along glycolytic pathway or the pentose phosphate pathway. it can be hydrolysed by glucose-6-phosphate to glucose

Question 21

Glycogen synthesis

Answer 21

G6P produced by gluconeogenesis may not be hydrolysed to glucose but may be converted to G1P for incorporation into glycogen
Makes α(1-4) linkages
Only extends existing chain so glycogenic attaches to glucose would be a linear compound but glycogen is branched