How is kyotorphin (Tyr-Arg) generated in the brain?
Kyotorphin (Tyr-Arg) was rapidly degraded in the brain homogenates and purified membrane-bound aminopeptidase from monkey brains. The degradation of kyotorphin by these preparations was effectively inhibited by bestatin. When brain homogenates or slices were incubated with bestatin, kyotorphin was accumulated time-dependently in a rate of 1.0 or 2.1 pmol/mg protein/hr, respectively. The bestatin-induced kyotorphin accumulation was inhibited by leupeptin, p-chloromercuribenzoate, but not phenylmethylsulfonylfluoride or diisopropylphosphate. The kyotorphin accumulation was concentrated in the P2 (crude mitochondrial) fraction, particularly in the particulate or synaptosomal fraction. These findings suggest that kyotorphin may be generated in vitro from precursor proteins by membrane-bound, leupeptin-sensitive "kyotorphin converting enzymes" in close vicinity to membrane-bound aminopeptidase which rapidly degrades kyotorphin generated.
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D004723:Endorphins / Q000096:biosynthesis*; D007031:Hypothalamus / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D004723:Endorphins; C019448:kyotorphin; D007930:Leucine; C012211:ubenimex