Introduction to Metabolism Common Catabolic Pathway
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3
Cell structure 4
Catabolism proteins amino acids polysaccarides simple sugars lipids glycerol fatty acids pyruvate acetyl Co. A Krebs Cycle CO 2 AH 2 O 2 H 2 O
Oxidative decarboxylation of pyruvate 6
Oxidative decarboxylation of pyruvate 7
Pyruvate dehydrogenase complex 8
Pyruvate dehydrogenase Vitamin B 1 (thiamine) Thiamine pyrophosphate
Dehydrolipoyl transacetylase
Dihydrolipoyl dehydrogenase FAD 11
+ NAD
Coenzyme A Residue of pantothenic acid
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15
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E 3 -FAD H 2 + NAD+ E 3 -FAD + NADH + H+ 17
Krebs cycle Respiratory chain 18
Regulation of PDH complex inactive 19
Cell Energy Charge 20
Pyruvate dehydrogenase complex defects • Pyruvate dehydrogenase deficiency (Xlinked dominant defect): congenital lactic acidosis. Nervous system problems. • Phosphatase deficiency: lactic acidosis. • Arsenic poisoning (lewisite - an arsenicbased chemical weapon): blocks lipoic acid causing neurologic disturbances and death. 21
Hans Adolf Krebs (1900 – 1981) 22
Citric acid cycle 23
Aconitase 24
Isocytrate dehydrogenase 25
α-ketoglutarate dehydrogenase complex 26
Succinyl-Co. A synthetase 27
succinate dehydrogenase fumarase 28
malate dehydrogenase 29
Overall equation: ++ FAD Acetyl-Co. A + 3 NAD + GDP + Pi + 2 H 2 O → + + HSCo. A + 3 NADH + 3 H FAD H 2 + GTP + 2 CO 2 30
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Control of the Krebs Cycle 32
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Efflux of intermediates from the TCA cycle 34
Pyruvate carboxylase reaction (anaplerotic reaction) 35
Vitamins and minerals required for the TCA cycle and anaplerotic reactions • • • Niacin (NAD) Riboflavin (FAD) Pantothenate (Co. A) Thiamine Biotin Mg 2+ Ca 2+ Fe 2+ Phosphate 36
TCA mistakes • Malate dehydrogenase gene mutation: effect on the development and growth of the fetus. Prenatal lethality. • Fumase deficiency: autosomal dominant mutation. Causes hereditary leiomyomatosis and renal cell cancer. • Succinate dehydrogenase deficiency in skeletal muscle causes mitochondrial myopathy with brain involvement, cardiomyopathy, and/or exercise intolerance. 37
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