A STUDY OF SELECTED CATECHOLAMINE METABOLIZING ENZYMES: A COMPARISON OF DEPRESSIVE SUICIDES AND ALCOHOLIC SUICIDES WITH CONTROLS¹

Abstract

The regional distributions of monamine oxidase (MAO) (EC 1.4.3.4), catechol-0methyltransferase (COMT) (EC 2.1.1.6), tyrosine hydroxylase (TH) (EC 1.14.3.2), and dopamine-Phydroxylase (DBH) (EC 1.14.2.1) have been examined in human brains obtained at autopsy from persons who died of natural causes (controls), and from persons who committed suicide and were further categorized as suffering from affective disorder (depression) or from alcoholism. Post mortem animal studies showed no changes in M A 0 or COMT activities in rabbit brain or in DBH activity in rat brain when the intact bodies were left at room temperature up to 24 h. T H activity in rabbit brains, however, began to decline immediately after death and after 24 h at room temperature it was approximately 48 per cent of the fresh brain level. There was no significant variation in activity of COMT, TH and DBH in human brain attributable to age or sex. M A 0 activities in the 60-70 yr decade were 34 per cent higher than in the 30-40 yr decade. M A 0 activities were highest in the hypothalamus and substantia nigra, T H activities were highest in substantia nigra, putamen and head of caudate, and DBH activities were greatest in tegmentum of pons and hypothalamus. Only minimal regional differences in COMT activities were observed. No significant differences were found between enzyme activities in brain areas of controls and suicides with the possible exception of T H in the substantia nigra, where the depressive suicides (but not the alcoholics) showed greater activity ( P < 0.02). These findings appear not to support the catecholamine hypothesis of affective disorder.

Ageing and the nigrostriatal dopaminergic system

“…Although few studies have focussed specifically on the striatum, in vitro data are indicative of significant age related increases in MAO-B enzyme activity (Grote et al, 1974;Robinson et al, 1977;Fowler et al, 1980;Saura et al, 1997). Equivocal findings (Domino et al, 1973) can be explained by small sample size and lack of differentiation between the two MAO isoforms.…”

“…The decline was exponential, with the most substantial losses occurring between the ages of 5-25 yrs. Some studies have also reported equivocal or negative results, but as they employed non-standardized dissection methodology (Robinson et al, 1977), or the use of older sample groups which could not be expected to explore the effects of loss in early adult life (Grote et al, 1974;Mackay et al, 1978a), this may explain inconsistencies in findings. The predominant limitation of studies of this type is the extreme sensitivity of TH to pre-and post-mortem conditions, estimations of enzyme activity being particularly affected by the interval between death and freezing of tissue (McGeer et al, 1971(McGeer et al, , 1976.…”

Synthesis of a Biochemically Important Aldehyde, 3,4-Dihydroxyphenylacetaldehyde

“…The measurement of DOPAL will therefore contribute to a more accurate estimation of premortem levels of DA in postmortem human brain. In addition, because the enzymes involved in metabolism of DOPAL (aldehyde reductase, aldehyde dehydrogenase, and catechol-O-methyltransferase) either are in very low amounts (9) or are extraneuronal (10)(11)(12), DOPAL may be an index of the intraneuronal metabolism of newly formed DA (13).…”

Effects of Ethanol on the Activity of Brain Enzymes

“…However, substantial variability in absolute levels of platelet MAO activity has been noted in alcoholic and control populations [95,100], and MAO activity was also found to fluctuate significantly after cessation of alcohol intake by the alcoholic [95,99], pos sibly due to changes in platelet production. As a result, platelet MAO activity is not always found to be lower in alcoholics than controls [101], and is not a reliable identifier of alcoholic individuals. This conclusion is…”