Lecture 27- glycogenesis & biosynthesis of glucose, glycogen & starch Flashcards
When is gluconeogenesis required?
When you can’t get glucose from your diet and your liver is depleted
Uses non-carbohydrate precursors
Occurs in liver and kidney
Gluconeogenic precursors
Molecules that can be used to produce a new synthesis of glucose
Includes glycolysis intermediates, citric acid cycle intermediates, carbon skeleton of amino acids
Precursor: glycerol
Released during hydrolysis of triacylglycerols
It is phosphorylated by glycerol kinase to glycerol phosphate
This is oxidised by glycerol phosphate dehydrogenase to dihydroxyacetone phosphate
Precursor: lactate
Produced in exercising muscle when ATP demand exceeds supply
Transferred to the liver, converted to pyruvate, then glucose
Known as ‘The Cori Cycle’
Futile cycle
Creates products only for them to be broken down
Precursor: amino acids
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
Metabolism of some amino acids
α-ketoacids formed from glycogenic amino acids
Enter TCA cycle and form oxaloacetate
Others form acetyl CoA (irreversible reaction)
Gluconeogenesis pathway
Occurs in mitochondria & cytosol
Seven glycolysis reactions run in reverse
3 reactions are irreversible- large -ve free energies, overcome by 4 gluconeogenic enzymes
Pyruvate carboxylase
Catalyses a highly exergonic reaction
Needs a free energy input to overcome it
Needs 2 enzymes- pyruvate carboxylase & PEPCK
Pyruvate carboxylase steps
- CO₂ is activated and transferred by pyruvate carboxylase to its biotin prosthetic group
- The enzyme then transfers the CO₂ to pyruvate, generating oxaloacetate
- oxaloacetate cannot cross the mitochondrial membrane so it is reduced to malate that can
PEP Carboxykinase (PEPCK)
Phosphoenolpyruvate carboxykinase
Monomeric enzyme (610 residues)
Catalyses the decarboxylation/phosphorylation of oxaloacetate
Located in mitochondria & cytosol in humans
Gluconeogenesis membrane transport
Oxaloacetate -> malate -> oxaloacetate route favoured
Produces cytosolic NADH
Steps of gluconeogenesis
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)
Regulation of gluconeogenesis
Gluconeogenesis & glycolysis are reciprocally regulated
3 substrate cycles are good points for regulation
Glycogen main stores
Skeletal muscle & liver
In muscle it serves as a fuel reserve for ATP synthesis
Glycogen structure
Has one reducing end but a non-reducing end on every branch (so rapid mobilisation)
Glycogen degradation
Separate cytosolic enzymes required
3 enzymes involved: glycogen phosphorylase, glycogen deb ranching enzyme, phosphoglucomutase
Glycogen phosphorylase
Binds pyridoxal-5’ phosphate
Enzyme activity: allosteric interactions & covalent modification, induces conformational change
Glycogen debranching enzyme
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
Phosphoglucomutase
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
Glycogen synthesis
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