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K F Tipton

Publications and source records attributed to K F Tipton.

276 records · Page 16Linked to original sources
PubMedDate not supplied

Subcellular distribution of aldehyde dehydrogenase activities in human liver.

The subcellular distributions of aldehyde dehydrogenase activities towards acetaldehyde have been determined in wedge-biopsy samples of human liver. A form with Km values of less than 1 microM and 285 microM towards acetaldehyde and NAD+ respectively was present in the mitochondrial fraction. This enzyme had no detectable activity towards N-tele-methylimidazole acetaldehyde, the aldehyde derived from the oxidation of N-tele-methylhistamine. The activity in the cytosol was more sensitive to inhibition by disulfiram and had Km values of 270 microM and 25 microM for acetaldehyde and NAD+, respectively. It was active towards N-tele-methylimidazole acetaldehyde with a Km value of 2.5 microM and a maximum velocity that was 40% of that determined with acetaldehyde. Both these cytosolic activities had alkaline pH optima.

Aldehyde Dehydrogenase↗
PubMedDate not supplied

Platelet MAO activity in subtypes of alcoholics and controls in a homogenous population.

The level of platelet monoamine oxidase (MAO) activity has been found to vary between alcoholics and healthy controls and between subtypes of alcoholics, in different populations. This study measured the MAO activity in a group of 46 abstinent alcohol dependent subjects and 22 healthy non-alcoholic controls, male and female, in an ethnically homogenous Irish population. The healthy control subjects had a mean MAO activity of 0.27 pmol/hr/10(5) platelets (+/- SEM 0.03), while the alcoholics overall had a mean activity of 0.34 pmol/hr/10(5) platelets (+/- 0.03) and this difference was not significant, P = 0.2. When the alcoholic group was divided into subtypes of alcoholism, (type 1 and type 2) there was no difference between subtypes of alcoholics nor between each subtype and the controls in their MAO activity. There was no correlation between MAO activity and the age of the subjects, the duration of abstinence from alcohol, the severity of alcoholism, smoking status or the gender of the subjects. These data are discussed in the context of the current literature on alcoholism and platelet MAO in different ethnic populations and the status of platelet MAO as a potential marker for alcoholism.

Adult↗
PubMedDate not supplied

Trait markers for alcoholism: clinical utility.

Because alcoholism is a multi-factorial psychiatric disorder, with both psychosocial and biochemical/genetic factors leading to its manifestation in any one individual, the presence of biochemical/genetic factors alone may not lead to the manifestation of the disorder. There are numerous difficulties associated with identification of a trait abnormality in a disorder that requires suitable socio-cultural permissiveness with distinct behavioural characteristics to manifest a disorder that may not require that predisposing trait abnormality in order to develop. Numerous studies have been performed in the past to potentially identify a biochemical or genetic trait abnormality in alcoholism, and not all of them have addressed significant methodological flaws in this type of research. This review addresses some of the difficulties inherent in this research, and aims for a comprehensive review of the highlights of the search for a clinically useful trait abnormality. Some series of investigations hold promise that a trait marker for a particular subset of alcoholics may be developed, e.g. severe alcoholism and the dopamine D2 receptor gene; the level of reaction to alcoholism in family history-positive alcoholics; beta-endorphin abnormalities in specific family groups of alcoholics; reduced P3 wave event-related potentials as markers and predictors of development of substance abuse in predisposed youths; reduced growth hormone response to apomorphine as a predictor of relapse to alcoholism in early abstinence; abnormal adenylyl cyclase activity in certain defined subgroups of alcoholics; and abnormal platelet monoamine oxidase levels in subjects with a behavioural predisposition to addictive disorders. The review concludes that while there has not yet been an identification of a comprehensive trait marker for alcoholism, there is hope for identification subgroups of alcoholics with consistent biological markers within that subgroup that may well prove fruitful over time. It will then be up to a future generation of clinicians to take that information and develop prevention programmes that can incorporate this information to help the predisposed individual avoid alcohol problems.

Alcoholism↗
PubMedDate not supplied

[Oxidative modification of monoamine oxidase].

Oxidative modification of monoamine oxidases (MAO) accompanied by alteration of their substrate specificity and sensitivity to specific inhibitors was discovered by Professor V.Z. Gorkin more than 30 years ago. The mechanism of this phenomenon includes oxidation of SH groups of the enzyme. Oxidative modification of MAO is also accompanied by increased sensitivity to limited proreolysis. Modification of MAO was found in many pathological states, however, elucidation of biological role of this phenomenon requires further investigations.

Animals↗
PubMedDate not supplied

[Monoamine oxidase inhibitors and pressor response to dietary amines].

Because gastro-intestinal monoamine oxidase (MAO) effectively prevents dietary pressor amines, typically tyramine, from entering the tissues, a marked hypertensive response (the "cheese reaction") can occur when subjects treated with antidepressant MAO inhibitors ingest foods or beverages rich in such amines. Although tyramine is a substrate for both MAO-A and -B, it is only inhibitors of the former enzyme, which are also the effective antidepressants, that give rise to the cheese reaction. This has be shown to be owing to MAO-A being the major form of MAO in intestine and stomach. Selective inhibition of that form of the enzyme results in substantial amounts of unchanged tyramine passing through the intestine. The development of reversible inhibitors of monoamine oxidase-A (RIMAs) has reduced this hypertensive response since rising tyramine concentrations can displace the inhibitor from the enzyme and thus allow some metabolism to occur. This has led to the development of MAO-inhibitory antidepressants that may, apparently, be used without dietary restriction. However, reversibility of the inhibitory process is not sufficient and the analysis of inhibitory behaviour presented here indicates that such safety will only be obtained with inhibitors that are competitive with respect to the amine substrates. Noncompetitive inhibitors might be expected to offer no safety advantage in this respect, whereas uncompetitive could actually exacerbate the pressor response.

Blood Pressure↗