Biochemistry of Liver Flashcards
Glucose
- Each day ~160 g of glucose is oxidised where 75% is consumed by the brain alone
- Rapid and dramatic falls in blood glucose can lead to acute neuroglycopaenia
Glycogenesis
Formation of glycogen from glucose
Regulation of Glycogenesis
Glycogen Synthase
- Glucagon stimulates the phosphorylation of the serines resulting in the formation of GS-b
- Insulin activates protein kinases which phosphorylate and inactive GSK promoting the formation of GS-a
- Glucose-6-phosphate allosterically enhance the action of PP1
Glycogenolysis
It would be disadvantageous for synthesis and degradation of glycogen to occur simultaneously => Therefore same cAMP cascade which inhibits glycogen synthesis stimulates glycogenolysis
- Enzyme breaks 1,6 alpha linkage
Gluconeogenesis
Synthesis of glucose from non-carbohydrate precursors:
- Glycerol, lactate, amino acids
High endogenic
1) Oxaloacetate formation in mitochondria
2) Converted into malate / PEP and transported into cytosol
3) The next few steps of the reaction the reverse of glycolysis
4) Fructose 1,6-bisphosphate is converted to fructose 6-phosphate by fructose 1,6-bisphosphatase
5) Glucose-6-phosphate is hydrolysed by glucose-6-phosphatase to produce glucose
AA Catabolism
Transamination and deamination
By product (NH4+) detoxified in urea cycle
Non-essential AA synthesis
- Synthesized by body, essential obtained from diet
- Often catalysed by transaminases (or aminotransferases)
- Formed from 3-phosphoglycerate, pyruvate, oxaloacetate and α-ketoglutarate
Lipid Metabolism
Acetyl - CoA:
- FA synthesis => triglyceride formation, Synthesis of cholesterol, phospholipids and lipoproteins
FA Synthesis
- synthesised from glucose derived acetyl-CoA
- When glucose is plentiful, acetyl-CoA is sufficient for the TCA cycle
- Citrate is transported out of the mitochondria and converted to acetyl-CoA and oxaloacetate by citrate lyase
- Acetyl-CoA remains in the cytosol and is available for fatty acid synthesis
Desaturation
- Caused by fatty acyl-coA desaturases
- In SER
Enzymes in formation and breakdown of FA
Acetyl-CoA + ATP + HCO3- Malonyl-CoA + ADP
- Regulates breakdown of FA#
FA synthetase
Ketogenesis
Ketone bodies are produced by the breakdown of fatty acids and ketogenic amino acids:
- Acetone, acetoacetate. b-hydroxybutyrate
Ketogenesis Regulation
1) Lipolysis in the adipose tissue (induced by glucagon)
2) Activity of carnitine palmitoyltransferase I (CPT-1)
3) Fate of Acetyl-CoA – determined by the concentration of OAA
Urea Synthesis
1) Transamination to Glutamate
2) Deamination (glutamate dehydrogenase)
3) NH3 produced rapidly removed by the liver and converted to urea
Detoxification
Ornithine Cycle
- Urea excreted by kidneys
- Some diffuse into intestine
Detoxification - Drugs + Poisons
Xenobiotics = Substances not normally present in body
- Liver is responsible for neutralizing xenobiotics – modifying chemical constitution
The overall effect of the Phase I and Phase II reactions are to:
- Increase acidity (lower pKa)
- Increase solubility
- Decrease the toxicity
