Regulation of carbohydrate metabolism Flashcards
Glycolysis
Metabolises glucose to produce:
- energy in the form of ATP by substrate level and oxidative phosphorylation
- glycerol-3-phosphate for fat synthesis
- amino acids
Regulation occurs primarily at the level of glucose transport into the cell, PFK-1 and pyruvate kinase
Gluconeogenesis
Glucose synthesis from non- carbohydrate precursors:
- lactate from glycolysis
- amino acids from protein breakdown
- glycerol from fat metabolism
Occurs in liver
Maintains blood glucose during fasting, starvation, depletion
Has unique enzymes to overcome unfavourable reactions and introduce points of control
Regulation of glycolysis
PFK-1 subject to energy dependent allosteric regulation by ATP, AMP and H+
ATP inhibits- prevents glucose being utilised by glycolysis when ATP is available
AMP leads to activation- competes with ATP, increases glycolysis and energy production
Regulation of PFK-1 by H+ ions
H+ increased during anoxia or anaerobic muscle contraction as result of lactic acid production
Inhibits glycolysis to prevent cellular pH falling too low and damaging the cellular machinery
In heart can be overcome by high AMP resulting in cellular damage and chest pains experienced in heart attacks and angina
Regulation of PFK-1 by nutrients
Fru-6-P activates- sign of high rates of glucose entry or glycogen breakdown, stimulates glycolysis to allow utilisation for energy production or fat synthesis
Fru-2,6-P2- sign of high rates of glucose entry or glycogen breakdown and leads to activation, most potent allosteric activator known
Citrate inhibits- signals TCA cycle overload or fatty acid oxidation and the need to conserve glucose by inhibition of glycolysis
Fructose 2,6 bisphosphate
Synthesised from F-6-P by the enzyme 6-phosphofructo-2-kinase (PFK-2)
Most potent allosteric activator PFK-1
Not involved in metabolic pathways: acts solely to reinforce allosteric control on PFK-1
Glycolysis is inhibited by
Present of sufficient energy (ATP)
Fatty acid oxidation indicating the need for glucose sparing
H+ ions
Glycolysis is activated by
Low levels of energy (AMP)
Lots of glucose or its metabolites
Fructose-2,6-bisphosphate in liver
Has to control glycolysis at the level of PFK1
Controls reverse reaction of gluconeogenesis at F-1,6,BPase
Neither PFK-1 nor F-1,6-BPase are directly controlled by hormones through phosphorylation but by level of F-2,6-BP which is affected by hormones
PFK-2 and F-2,6-BPase are single tandem enzymes with two active sites
Phosphorylation inhibits PFK-2 and stimulates F,2,6-BPase
Regulation of gluconeogenesis
Stimulated short term by glucagon and adrenaline by changes in protein phosphorylation or mobilisation of fatty acids and production of acetyl CoA
Long term stimulation occurs through enzyme induction by glucagon, glucocorticoids and thyroid hormones
Inhibited acutely by insulin via dephosphorylation and suppression of lipolysis and in the long term by suppression of gluconeogenic enzymes
Control of gluconeogenesis
Increased fatty acid oxidation so increase in acetyl CoA- allosteric activator of pyruvate carboxylase and inhibitor of pyruvate dehydrogenase- favours gluconeogenesis
Increased glucagon inhibits PFK-2 activity and stimulates F-2,6-BPase by phosphorylation resulting in fall in F-2,6-BP
Decreased F-2,6-BP level reduces activation of PFK-1 and relieves inhibition of F-1,6-BPase
The urea cycle
To use amino acids as source of carbon skeletons for glucose, must first by transaminated to lose their ammonia
Toxic to cells, eliminated from body
Converted to urea in the liver then passed out into the bloodstream and excreted by kidneys
Fumarate converted to oxaloacetate in cytoplasm generating substrate for gluconeogenesis
Increased rates of gluconeogenesis always coupled with increased rates of urea synthesis
