T2 L8 Regulation of carbohydrate metabolism Flashcards
What does glycolysis produce?
Energy in the form of ATP by substrate level & oxidative phosphorylation
Glycerol-3-phosphate for fat synthesis
Acetyl CoA for fat & cholesterol synthesis
Amino acids
What does PFK-1 do?
Phosphofructokinase 1 catalyses the first step in glycolysis
What are some non-carbohydrate precursors that are used for de novo glucose synthesis?
Lactate from glycolysis
Amino acids from protein breakdown
Glycerol from fat metabolism (not fatty acids)
Where does gluconeogenesis occur?
Liver
Kidneys
What is the function of gluconeogenesis?
Maintains blood glucose during fasting, starvation or when glycogen reserves are depleted to preserve glucose-dependent cerebral function & red blood cell metabolism
What are some enzymes that regulate gluconeogenesis?
Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose-1,6-bisphosphate
Glucose-6-phosphatase
What does gluconeogenesis require?
Energy from the metabolism of fatty acids released from adipose tissue
Carbon skeletons from lactate, amino acids or glycerol released from triglycerides by lipolysis in adipose tissue
What does ATP do to glycolysis?
It inhibits glycolysis
Sign of high energy levels in the muscle
Prevents glucose being used by glycolysis when ATP is available
Co-ordinates glycolysis with glycogen breakdown via phosphorylase
What does AMP do to glycolysis?
It is present when ATP is depleted such as during muscle contraction or anoxia
Competes with ATP
Increases glycolysis & energy production
Co-ordinates glycolysis with glycogen breakdown via phosphorylase
What converts Fru-6-PO4 to Fru-1,6-(PO4)2?
6-phosphofructose-1-kinase
What converts Fru-1,6- (PO4)2 to Fru-6-PO4?
Fructose-1,6-bisphosphate
Why does H+ increase during anoxia or anaerobic muscle contraction?
Due to lactic acid production
What does H+ do to PFK-1?
It regulates it
H+ inhibit glycolysis to prevent cellular pH falling too low & damaging cellular machinery
In the heart H+ can be overcome by a high AMP which leads to cellular damage & chest pains experienced in heart attacks & angina
How can PFK-1 be regulated?
H+ ions
Nutrients such as fructose-6-phosphate, fructose-2,6-bisphosphate, citrate
What does fructose-6-phosphate do to PFK-1?
It activates it
Sign of high rate of glucose entry or glycogen breakdown
Stimulates glycolysis to allow utilisation for energy production or fat synthesis
What does fructose-2,6-bisphosphate do to PFK-1?
Activates it
Sign of high rate of glucose entry or glycogen breakdown
Most potent allosteric activator known
Stimulates glycolysis to allow utilisation for energy production or fat synthesis
What does citrate do to PFK-1?
It inhibits it
Signals TCA cycle overload - more acetyl CoA than can be oxidised
Or signals fatty acid oxidation & the need to conserve glucose by inhibiting glycolysis
What does F-6-P do to fructose-2,6-bisphosphate?
It activates it Increase in glucose concentration Increase in glycogen breakdown in the muscle AMP - increased contraction Glycolysis is activated
What does citrate do to fructose-2,6-bisphosphate?
Inhibits it
Increased fatty acid oxidation - TCA cycle overload
Glycolysis is inhibited
How is glycolysis inhibited?
Presence of sufficient energy ATP
Fatty acid oxidation
H+ ions - lots of lactate present
How is glycolysis activated?
Low levels of energy - AMP
Lots of glucose or its metabolites
How is gluconeogenesis stimulated in the short term?
Glucagon & adrenaline by changes in protein phosphorylation or mobilisation of fatty acids & production of acetyl CoA
How is gluconeogenesis stimulated in the long term?
Occurs through enzyme induction by glucagon, glucocorticoids & thyroid hormones
How is gluconeogenesis acutely inhibited?
By insulin via dephospho rylation & suppression of lipolysis
How is gluconeogenesis inhibits in the long term?
Suppression of gluconeogenic enzymes
What is the equation for the conversion of ammonia to urea?
NH3 + CO2 + 2H2O + 3ATP + aspartate –> urea + fumarate + 2ADP + AMP + 2Pi + PPi
Where is fumarate converted to oxaloacetate?
In the cytoplasm
Generates substrate for gluconeogenesis
How is glycolysis regulated?
At the level of glucose transport into the cell, PFK-1 & pyruvate kinase
