Biochem and medical genetics
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| Key points | show 🗑
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| Where does this fit in | show 🗑
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| What does the krebs cycle do | show 🗑
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| What are NADH and FADH2 | show 🗑
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| Use of NADH | show 🗑
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| Use of FADH2 | show 🗑
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| show | Acetyl CoA combines with oxaloacetate to form citrate
Citrate forms isocitrate
Decarboxylated to from alpha ketoglutarate then succinyl-CoA releasing Co2 and NADH
SLP into succinate releasing GTP
Converted to fumarate, malate and back to oxaloacetate
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| show | Citrate synthase
Aconitase
Isocitrate dehydrogenase
Alpha ketoglutarate dehydrogenase
Succinyl CoA synthase
Succinate dehydrogenase
Fumarase
Malate dehydrogenase
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| Key reactions | show 🗑
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| What energy does this produce | show 🗑
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| show | Fatty acids - beta oxidation
Ketone bodies - ketone body oxidation
Amino Acids - amino acid degradation
Sugars - glycolysis and PDH
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| Pyruvate dehydrogenase | show 🗑
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| Pyruvate transport into mitochondria | show 🗑
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| Oxidative decarboxylation of pyruvate | show 🗑
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| Pyruvate dehydrogenase complex | show 🗑
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| show | Irreversible
Costs energy
Committed steps - point of no return
Energy sensing
Cannot resynthesis glucose past this point
Inhibited by ATP and stimulated by ADP
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| Control of PDH | show 🗑
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| Arsenic poisoning | show 🗑
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| show | Combined by citrate synthase to form citrate
Condensation reaction
Inhibited by ATP, Citrate, NADH, succinyl CoA FA CoA
Activated by ADP,
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| Citrate - formed isocitrate | show 🗑
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| show | Mutations in IDH1/2 are found in 60-90% of secondary gliomas and 12-18% of leukaemia
Originally thought to be blockage of TCA cycle leading to Warburg effect
Shown that mutations lead to production of 2-HG - an oncometabolite
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| show | Converted to succinyl CoA by alpha ketoglutarate dehydrogenase
Oxidative carboxylation
Uses lipoic acid and thiamine pyrophosphatase as coenzymes
Releases CO2 and NADH
Activated by Ca
Inactivated by ATP, GTP, succinyl CoA and NADH
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| BeriBeri | show 🗑
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| Succinyl CoA | show 🗑
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| show | Phosphoryl donor in protein synthesis, gluconeogenesis
Signal transduction
Translocation of proteins into mitochondrial matrix
Conversion to ATP via nucleoside diphosphokinase
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| Succinate | show 🗑
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| Succinate dehydrogenase | show 🗑
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| Accumulation of succinate in ischaemia | show 🗑
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| show | Converted to oxaloacetate by malate dehydrogenase
Oxidation
Releases NADH
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| show | Studied process of respiration on breast muscle of pigeons
Minced the tissue and showed it took up oxygen rapidly
Oxygen uptake was rapidly increased when carbohydrates of their C3 products were added
Also true for C4 salts
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| Evidence - Krebs and Johnson | show 🗑
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| Why a cycle | show 🗑
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| Control via calcium | show 🗑
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| Other roles of the TCA cycle | show 🗑
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| Disadvantages of the cycle | show 🗑
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