regulation of carbohydrate metabolism Flashcards
where does glycolysis occur?
in all tissues
what is glycolysis important?
energy in the brain and red blood cells and also for contracting skeletal muscle
what percentage of the body’s total usage of glucose is by red blood cells?
10%
what are the 3 examples of de novo glucose synthesis from non-carbohydrate precursors?
1) lactate from glycolysis
2) amino acids from protein breakdown
3) glycerol (but NOT fatty acids) from fat metabolism
where does gluconeogenesis?
liver and the kidney
what does gluconeogenesis do?
maintains blood glucose during fasting, starvation or when glycogen reserves are depleted to preserve glucose-dependent cerebral function and red blood cell metabolism
why isn’t gluconeogenesis just the reverse of glycolysis?
it has a unique set of enzymes to overcome energetically unfavourable reactions and introduce points of control
what are the requirements for gluconeogenesis?
1) a source of carbon for formation of glucose molecules
2) a source of energy for biosynthesis
where do you get the source of carbon for gluconeogenesis?
it is provided for lactate, amino acids or glycerol released from TGs by lipolysis in adipose tissue
where do you get the source of energy for gluconeogenesis?
provided by metabolism of fatty acids released by lipolysis in adipose tissue
what must happen first for amino acids to be used in glucose production?
it must first be transaminated to lose their ammonia
why must ammonia be eliminated from the body?
it is toxic to cells
what happens to ammonia so it isn’t toxic to the cells?
it is converted to urea in the liver and then passed out into the bloodstream and extremed by the kidney
what is the equation for the conversion of ammonia to urea?
NH3 + CO2 + 2H2O + 3ATP + aspartate —> urea + fumarate
what is fumarate converted to?
oxaloacetate
what overcomes the irreversible steps in glycolysis?
expression of gluconeogenetic enzymes
what are the 3 stages of glycolysis?
1) glucose
2) glucose broken down
3) pruvate
what are the 3 stages of gluconeogenesis?
1) oxaloacetate (pyruvate)
2) glucose formed
3) glucose
what allosterically regulates PFK-1?
- ATP
- AMP
- H+
what affect does ATP inhibition have on the regulation of glycolysis?
- sign of high energy levels in muscle
- prevents glucose being utilised by glycolysis when ATP is available
- co-ordinates glycolysis with glycogen breakdown via phosphorylase
what role does AMP have on the regulation of glycolysis?
- leads to activation
- competes with ATP
- increases glycolysis and energy production
- co-ordinates glycolysis and glycogen breakdown via phosphorylase
how is PFK-1 regulated by H+?
- H+ increased during anoxia or anaerobic muscle contraction as a result of lactic acid production
- inhibits glycolysis to prevent cellular pH falling too low and damaging the cellular machinery
- in heart it can be overcome by high AMP in cellular damage and chest pains experienced in heart attacks and angina
how is PFK-1 regulated by nutrients?
- PFK-1 is also subject to regulation by Fru-6-P, Fru-2,6-BP and citrate
- Fru-6-P activates which is a sign of high rates of glucose entry or glycogen breakdown. stimulates glycolysis to allow utilisation for energy production or fat synthesis
- Fru-2,6-BP is also a signal of high rates of glucose entry or glycogen breakdown and leads to activation. stimulates glycolysis to allow utilisation for energy production or fat syntheis
- citrate inhibits which signals TCA cycle overload or fatty acids oxidation and the need to conserve glucose by inhibition of glycolysis
what is the most potent allosteric activator known?
Fru-2,6-BP
what synthesises Fructose-2,6-biphosphate?
synthesises from F-6-P by the enzyme PFK-2
what is the most potent allosteric activator of PFK-1?
fructose-2,6-biphosphate
what does fructose-2,6-biphosphate do?
it isn’t involved in metabolic pathways - it acts solely to reinforce allosteric control on PFK-1
what is the energy status of ATP with the regulation of glucose at PFK-1?
- signal of maximum energy status
- keeps PFK-1 inhibited in the resting cell to conserve glucose
what is the energy status of AMP with the regulation of glucose at PFK-1?
- signal of reduced energy status
- stimulates glycolysis to increase cellular levels of ATP
- ensures that glycogenolysis and glycolysis are coordinated
what is the energy status of H+ ions with the regulation of glucose at PFK-1?
- raised during anoxia by lactic acid
- inhibits glycolysis to prevent cell pH falling and damaging cellular machinery
- can be overcome by AMP (heart)
what is the role of F-6-P in the nutrient regulation of glucose at PFK-1?
- signals glucose entry or glycogen breakdown
- stimulates PFK-1 and glycolysis for energy and fat synthesis
what is the role of F-2,6-P2 in the nutrient regulation of glucose at PFK-1?
- signals glucose entry or glycogen breakdown
- stimulates PFK-1 and glycolysis for energy and fat synthesis
what is the role of citrate in the nutrient regulation of glucose at PFK-1?
- signals TCA cycle overload or fatty acid oxidation
- need to inhibit glycolysis and conserve glucose
what is glycolysis inhibited by?
- presence of sufficient energy
- fatty acid oxidation indicating the need for glucose ‘sparing’
- H+ ions
what is glycolysis activated by?
- low levels or energy
- lots of glucose or its metabolites
what does the muscle use glucose and glycogen for?
energy production by increasing F-2,6-Bp and stimulating glycolysis
what does the liver use glucose produced via glujconeogeneis and glycogen for?
maintain blood glucose so glycolysis is inhibited
what is the role of fructose-2,6-biphosphate in the liver?
- PFK-2 and F-2,6-BPase are a single tandem enzyme with 2 active sites
- phosphorylation inhibits PFK-2 and stimulates F-2,6-BPase = decrease F-2,6-BP
- 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
what happens with the activation of gluconeogenesis?
- increased fatty acid oxidation leads to increase in acetyl CoA: an allosteric activator of pyruvate carboxylase and inhibitor of pyruvate dehydrogenase, so favours glujconeogeneis over glycolysis
- increased glucagon inhibits PFK-1 activity and stimulates F-2,6-BPase by phosphorylation resulting in a fall in F-2,6-BP
- decreased F-2,6-BP levels reduce activation of PFK-1 and receives inhibition of F-1,6-BPase
how is gluconeogenesis regulated by hormones?
stimulated in the short term by glucagon and adrenaline by changes in protein phosphorylation or mobilisation of fatty acids and production of acetyl CoA
how is gluconeogenesis hormonally regulated in the long term?
stimulation occurs through enzyme induction by glucagon, glucocorticoids and thyroid hormones
what acutely inhibits hormonal regulation of gluconeogenesis?
insulin by dephosphorlyation and suppression of lipolysis and in the long term by suppression of gluconeogenic enzymes
