REGIONAL DISTRIBUTION OF HOMOCARNOSINE, HOMOCARNOSINE‐CARNOSINE SYNTHETASE AND HOMOCARNOSINASE IN HUMAN BRAIN

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Abstract
Homocarnosine (HCarn) content varied over a 6‐fold range in different regions of autopsied human brain, being highest in the dentate nucleus and the inferior olive, and lowest in the caudate nucleus and mesolimbic system. HCarn content was similar in biopsied and autopsied frontal cortex. Very little if any carnosine (Carn) was present in human brain, except for the olfactory bulb, where Carn may have comprised 20% of the imidazole dipeptides present. Only HCarn was present in human CSF.HCarn‐Carn synthetase enzyme activity in biopsy specimens of human frontal and temporal cortex was approx 10 times greater than has been reported for rat cerebral cortex. The enzyme synthesized Carn 3–5 times as rapidly as HCarn, when β‐alanine (β‐Ala) or GABA substrate concentrations were 10 MM. The synthetase was found to have an apparent Km of 1.8 mM for β‐Ala, and 8.8 mM for GABA. HCarn‐Carn synthetase activity decreases rapidly after brain death, and was not detectable in autopsied brain specimens frozen more than 6 h after patients’deaths.Homocarnosinase activity was determined in brain, using L‐[γaminobutyryl‐1‐14C]HCarn as substrate, and measuring radioactive GABA produced by hydrolysis of HCarn at pH 7.2 in the presence of Co2+ ions. Homocarnosinase activity was similar in biopsied and autopsied human cerebral cortex, and appeared to be stable for at least 10 h after death in unfrozen brain.Differences in the regional distribution of HCarn‐Carn synthetase and homocarnosinase activities, as well as regional differences in GABA content in human brain, do not readily account for regional differences in HCarn content, nor do they suggest a physiological role for HCarn.