Regulation of carbohydrate metabolism Flashcards
What does glycoloysis produce?
Metabolizes glucose to produce:
- energy in the form of ATP by substrate level phosphorylation
- glycerol-3-phosphate for fat synthesis
- pyruvate for conversion to acetyl CoA for TCA cycle or fat and cholesterol synthesis
- amino acids
Where does regulation of glycoloysis occur?
•Regulation of glycolysis occurs primarily at the level of glucose transport into the cell, PFK-1 and pyruvate kinase (in the liver)
How is metabolism regulated?
- Glycogenolysis and glycogen synthesis are reciprocally regulated to avoid futile cycling of glucose
- Regulatory mechanisms are allosteric
Regulatory mechanisms are also hormonal
Why is it important for carbohydrate metabolism to be regulated?
- Glucose generated from glycogenolysis must be directed into the appropriate biological pathway (tissue specific)
- The opposing processes of glycolysis and gluconeogenesis must be reciprocally regulated
Which steps of glycoloysis differ from gluconeogenesis?
Glycolysis occurs in all tissues, particularly important for energy in brain and Rbc’s and also in contracting skeletal muscle. Rbc’s account for 10% of the bodies total usage. The irreversible steps (shown in red) are where the pathway differs from gluconeogenesis.
What is gluconeogenesis?
•De novo glucose synthesis from non-carbohydrate precursors e.g.
- lactate from glycolysis
- amino acids from protein breakdown
- glycerol (but NOT fatty acids) from fat metabolism
•Not a simple reversal of glycolysis, has unique enzymes to overcome energetically unfavourable reactions and introduce points of control
Where does gluconeogenesis occur?
•Occurs in liver (and kidney)
Why is gluconeogenesis important?
•Maintains blood glucose during fasting, starvation or when glycogen reserves are depleted to preserve glucose-dependent cerebral function and red blood cell metabolism
What are the 2 requirements for gluconeogenesis?
What is the role of the urea cycle?
- Increased rates of gluconeogenesis are always coupled with increased rates of urea synthesis
- To use amino acids as a source of carbon skeletons for glucose production, must first be transaminated to lose their ammonia.
What happens in the urea cycle?
•Ammonia is toxic to cells, so must be eliminated from the body. Converted to urea in the liver, then passed out into the bloodstream and excreted by the kidneys
NH3 + CO2 + 2H2O + 3ATP + aspartate -> urea + fumarate + 2ADP + AMP + 2Pi + PPi
•Fumarate is converted to oxaloacetate in the cytoplasm thereby generating a substrate for gluconeogenesis
What are the checkpoints in glycoloysis and gluconeogenesis?
How is glycoloysis regulated?
PFK-1 is subject to energy-dependent allosteric regulation by ATP, AMP and H+
- ATP inhibits - 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
- AMP (present when ATP is depleted e.g. during muscle contraction or anoxia) leads to activation. Competes with ATP. Increases glycolysis and energy production. Co-ordinates glycolysis with glycogen breakdown via phosphorylase
When is H+ increased?
•H+ increased during anoxia or anaerobic muscle contraction as a result of lactic acid production
How does increased H+ regulate PFK-1?
- 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
Complete the diagram on an extra level of control in glycoloysis
How is fructose 2,6 bisphosphate produced?
