Agmatinase activity in rat brain: a metabolic pathway for the degradation of agmatine.
Agmatinase, the enzyme that hydrolyzes agmatine to form putrescine and urea in lower organisms, was found in rat brain. Agmatinase activity was maximal at pH 8-8.5 and had an apparent K(m) of 5.3 +/- 0.99 mM and a Vmax of 530 +/- 116 nmol/mg of protein/h. After subcellular fractionation, most of the enzyme activity was localized in the mitochondrial matrix (333 +/- 5 nmol/mg of protein/h), where it was enriched compared with the whole-brain homogenate (7.6-11.8 nmol/mg of protein/ h). Within the CNS, the highest activity was found in hypothalamus, a region rich in imidazoline receptors, and the lowest in striatum and cortex. It is interesting that other agmatine-related molecules such as arginine decarboxylase, which synthesizes agmatine, and I2 imidazoline receptors, for which agmatine is an endogenous ligand, are also located in mitochondria. The results show the existence of rat brain agmatinase, mainly located in mitochondria, indicating possible degradation of agmatine by hydrolysis at its sites of action.
Sastre
M
M
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.
Regunathan
S
S
Galea
E
E
Reis
D J
DJ
D000376:Agmatine / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D001119:Arginase / Q000302:isolation & purification / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000201:enzymology; D002250:Carbon Radioisotopes; D002458:Cell Fractionation; D002531:Cerebellum / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D007031:Hypothalamus / Q000201:enzymology; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D011865:Radioisotope Dilution Technique; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000201:enzymology; D014316:Tritium; D014512:Ureohydrolases / Q000302:isolation & purification / Q000378:metabolism*
D002250:Carbon Radioisotopes; D014316:Tritium; D000376:Agmatine; D014512:Ureohydrolases; D001119:Arginase; C019625:agmatinase