4-aminobutyrate in mammalian putrescine catabolism.
The effects of inhibitors of diamine oxidase (EC 1.4.3.6), monoamine oxidase (EC 1.4.3.4) and 4-aminobutyrate aminotransferase (EC 2.6.1.19) on the catabolism of putrescine in mice in vivo were studied. Diamine oxidase inhibitors and carboxymethoxylamine (amino-oxyacetate) markedly inhibit the metabolism of [(14)C]putrescine to (14)CO(2), but affect different enzymes. Aminoguanidine specifically inhibits the mitochondrial and non-mitochondrial diamine oxidases, whereas carboxymethoxylamine specifically inhibits 4-aminobutyrate transamination by the mitochondrial pathway. Hydrazine inhibits at both sites, and results in increased concentrations of 4-aminobutyrate in brain and liver. Pretreatment of mice with carboxymethoxylamine and [(14)C]putrescine leads to the urinary excretion of amino[(14)C]butyrate. Carboxymethoxylamine does not affect the non-mitochondrial pathway of putrescine catabolism, as the product of oxidative deamination of putrescine in the extramitochondrial compartment is not further oxidized but is excreted in the urine as derivatives of 4-aminobutyraldehyde. Another catabolic pathway of putrescine involves monoamine oxidase, and the monoamine oxidase inhibitor, pargyline, decreases the metabolism of [(14)C]putrescine to (14)CO(2)in vivo. Catabolism of putrescine to CO(2)in vivo occurs along different pathways, both of which have 4-aminobutyrate as a common intermediate, in contrast with the non-mitochondrial catabolism of putrescine, which terminates in the excretion of 4-aminobutyraldehyde derivatives. The significance of the different pathways is discussed.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000613:Aminobutyrates / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors; D010293:Pargyline / Q000494:pharmacology; D011700:Putrescine / Q000378:metabolism*
D000613:Aminobutyrates; D005971:Glutamates; D008996:Monoamine Oxidase Inhibitors; D002245:Carbon Dioxide; D010293:Pargyline; D000612:4-Aminobutyrate Transaminase; D011700:Putrescine