17 - BCH 3120 lipid and amino acid metabolism zemin yao...

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zemin yao professor and chair e-mail: zyao@uottawa.ca BCH 3120 lipid and amino acid metabolism 03-14-11, Mon. 10:00-11:30 10:00-11:30 am
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glutamate NH 3 glutamate dehydrogenase NAD(P) + NAD(P)H + H + α -ketoglutarate citrulline ornithine P i arginino- succinate aspartate ATP AMP+PP i H 2 O urea arginine fumarate malate HCO 3 - carbamoyl phosphate 2ATP 2ADP+P i glutamate-aspartate transaminase review lecture 16 1. urea cycle
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review lecture 16 2. ornithine/citrulline transport ornithine ornithine citrulline citrulline ? ORNT1 ORNT2 mitochondrion cytosol carbamoyl-P
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human genetic disorders affecting amino acid catabolism via urea cycle medical condition approx. incidence (per 100,000 births) defective enzyme symptoms and effects argininemia < 0.5 arginase mental retardation argininosuccinic acidemia <1.5 argininosuccinase vomiting, convulsions carbamoyl phosphate synthestse 1 deficiency <0.5 carbamoyl phosphate synthetase 1 lethargy, convulsions, early death
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regulation of urea cycle reaction 1. alteration in enzyme expression according to dietary condition high protein diet prolonged starvation 2. N -acetylglutamate
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+ acetyl-CoA glutamate N -acetyl  glutamate synthase carbamoyl phosphate synthetase I is stimulated by N -acetylglutamate
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N -acetylglutamate CPS1 is activated by N -acetylglutamate the activity of N -acetylglutamate synthase is increased when acetyl-CoA and glutamate concentrations are high increased glutamate concentration is a result of increased amino acid breakdown formation of N -acetylglutamate represents a feed-forward regulation
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the glucose-alanine cycle
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recall: the Cori cycle utilization of lactate produced by anaerobic glycolysis in the muscles
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functional significance of muscle-liver transport of intermediates maintain sufficient concentrations of blood glucose through hepatic gluconeogenesis especially important during exercise and starvation the rate of recycling of glucose carbon skeletons in alaine-glucose cycle is at approximately 50% of that for the Cori cycle
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“Krebs bicycle” – linking urea and TCA cycles
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amino group removal - deamination disposal of amino group – urea cycle utilization of carbon skeleton amino acid deamination and the urea cycle (cont.)
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intermediates of amino acid breakdown gluconeogenic amino acids ketogenic amino acids
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17 - BCH 3120 lipid and amino acid metabolism zemin yao...

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