While most Caucasians have two main isozymes of liver aldehyde dehydrogenase, in about 50% of Orientals the ALDH I isozyme is missing. This isozyme, which has a faster electrophoretic mobility, is predominantly present in mitochondria and has a relatively low Km for acetaldehyde. The inherent deficiency of ALDH I is responsible for the impaired acetaldehyde oxidation leading to facial flushing and other cardiovascular symptoms of alcohol sensitivity commonly observed in Japanese and Chinese. Antibodies raised against apparently homogeneous liver ALDH I and ALDH II isozymes did not show an immunological similarity between the two isozymes which do not share common subunits. While erythrocyte ALDH II is also immunologically distinct from hepatic ALDH I, it showed an immunological similarity with hepatic ALDH II. On isoelectric focusing in agarose gel followed by immunoelectrophoresis, at least 4 components with an anti-ALDH I antibody were detected in extracts from Caucasian and Oriental livers. In Japanese livers deficient in ALDH I activity, the prominent ALDH component was missing. Apparently, more than one gene is responsible for the synthesis of ALDH isozymes reacting with an antibody against ALDH I. A deletion in one of the genes may be responsible for the loss of ALDH I enzyme activity and altered antigenic properties. However, at this stage, a point mutation in a structural gene coding for ALDH I resulting in a defective protein with altered electrophoretic and enzymatic properties is not ruled out.

Aldehyde Dehydrogenase↗

PubMedDate not supplied

Population genetic and family studies on aldehyde dehydrogenase deficiency and alcohol sensitivity.

Population genetic studies on the prevalence of aldehyde dehydrogenase isozyme I (ALDH I) deficiency in various Caucasian, Oriental, African, and American Indian subjects were carried out using hair roots as peripheral source of the enzyme activity. While a very high percentage of Orientals with Mongoloid origin were found deficient in ALDH I activity, no deficiency was detected in Caucasian and African populations. Native American Indians showed a relatively low incidence of ALDH I deficiency. A genetic model based on the phenotype determination using antisera against purified human liver ALDH I is proposed. Pedigree analysis of Japanese families suggests an autosomal codominant mode of inheritance.

Aldehyde Dehydrogenase↗

PubMedDate not supplied

Aldehyde dehydrogenase polymorphism and alcohol metabolism in alcoholics.

Significant differences in the incidence of aldehyde dehydrogenase isozyme I deficiency were observed between healthy controls and alcoholics in Japan. Only about 5% of alcoholics were found deficient as compared to about 42% in the normal healthy population. Blood acetaldehyde level after alcohol drinking was also found significantly higher in deficient subjects than in individuals without deficiency. Among alcoholics, deficient subjects showed relatively less elevated blood acetaldehyde levels. When two districts in Japan were compared, per capita alcohol consumption correlated with the frequency of isozyme deficiency. Higher percentage of aldehyde dehydrogenase isozyme deficiency was associated with lower per capita alcohol consumption. Thus, individuals deficient in aldehyde dehydrogenase isozyme may consume less alcohol.

Acetaldehyde↗

PubMedDate not supplied

Quantitative and qualitative biochemical parameters for alcohol abuse.

Blood from alcoholics, non-alcoholic patients and healthy controls were analyzed for various biochemical markers. Follow-up measurements were made during about 3 months of abstention. While a gradual increase in aldehyde dehydrogenase activity (ALDH) in red cell was noted in alcoholic patients serum alpha 1-acid glycoprotein (AAG) values returned to normal range within 8 weeks during abstinence. An additional minor band for alpha 1-antitrypsin (AAT) was observed after isoelectric focusing of sera from alcoholics; this band disappeared after 3 weeks of abstinence. However, no such unusual AAT band was found in non-alcoholic patients with liver disorders.

Alanine Transaminase↗

PubMedDate not supplied

13C-ethanol and 13C-acetate breath tests in normal and aldehyde dehydrogenase deficient individuals.

Four normal and five aldehyde dehydrogenase (ALDH) isozyme I deficient individuals were subsequently loaded with (1-13C)ethanol and (1-13C)sodium acetate and the conversion of the label to 13CO2 was determined in expired air by isotope ratio mass spectrometry. In the 13C-acetate breath test, both groups showed virtually identical recovery of the label in expired air, namely 48.5 +/- 2.3% (mean +/- S.D.) for normal and 46.8 +/- 5.7% for deficient individuals. However, in the 13C-ethanol breath test, both the groups performed differently. On average, although a certain overlap of the single data was observed, the recovery of the label after four hours was 43.4 +/- 3.8% for the normal and 35.6 +/- 6.8% for the ALDH deficient subjects. These findings suggest a slower conversion of ethanol to carbon dioxide in aldehyde dehydrogenase deficient individuals, which may be another consequence of this deficiency besides the higher plasma acetaldehyde levels observed after ethanol loading in comparison to individuals with normal aldehyde dehydrogenase activity.

Acetates↗

PubMedDate not supplied

Human brain aldehyde dehydrogenase: activity with DOPAL and isozyme distribution.

Aldehyde dehydrogenase (ALDH, EC 1.2.1.3), has been shown to be the most important enzyme for DOPAL metabolism in human brain (Agarwal et al.). In the present investigation cerebellum, corpus striatum and pons showed the highest ALDH activity. Most of the enzyme activity was found in the mitochondrial and microsomal fractions. Two activity bands on IEF gels and dual Km values indicate the presence of two distinct isozymes in all the fractions. Two cerebella from alcoholics yielded the same results as the control group regarding their total ALDH activity, subcellular distribution pattern and protein content. The presence of DOPAC (acid metabolite of DOPAL), pargyline, pyrazole or ethanol in the assay mixture did not alter the ALDH activity significantly.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Human liver aldehyde dehydrogenase: subcellular distribution in alcoholics and nonalcoholics.

Activity assay and isoelectric focusing analysis of human biopsy and autopsy liver specimens showed the existence of two major aldehyde dehydrogenases (ALDH I, ALDH II). Subcellular distribution of these isozymes was determined in autopsy livers from alcoholics and nonalcoholics. Nearly 70% of the total ALDH activity was recovered in the cytosol which contained both the major isozymes. Densitometric evaluation of isozyme bands showed that about 65% of the cytosolic enzyme activity was due to ALDH II and the rest due to ALDH I isozyme. Only about 5% of the total ALDH activity was found in the mitochondrial fraction (70% ALDH I and 30% ALDH II). Significantly reduced total and specific ALDH activities were noted in all the subcellular fractions from cirrhotic liver specimens. Apparently, ALDH I isozyme from cytosol and mitochondria is primarily responsible for the oxidation of small amounts of acetaldehyde normally found in the blood of nonalcoholics after drinking moderate amounts of alcohol. However, in alcoholics who exhibit higher blood acetaldehyde concentrations after drinking alcohol, ALDH II isozyme may be of greater physiological significance.

Alcohol Dehydrogenase↗

PubMedDate not supplied

Human aldehyde dehydrogenases: their role in alcoholism.

This article surveys the state of our knowledge concerning the biochemical and genetic variations in aldehyde dehydrogenases (ALDHs) in humans and their role in alcohol sensitivity, alcohol drinking habits, and alcoholism. Variations in acetaldehyde metabolism via genetically determined polymorphisms in ALDH enzymes seem to play an important role in individual and racial differences in acute and chronic effects of alcohol drinking as well as towards vulnerability to organ damage after chronic alcohol abuse. Alcohol sensitivity and associated discomfort symptoms accompanying alcohol ingestion may be determinantal for the significantly low incidence of alcoholism among Japanese, Chinese and other Orientals of Mongoloid origin. An abnormal ALDH isozyme has been found to be widely prevalent among individuals of Mongoloid race, and is mainly responsible for the acute sensitivity to alcohol commonly observed in this race. Persons sensitive to alcohol by virtue of their genetically controlled ALDH isozyme deficiency may be discouraged from drinking large amounts of alcohol in their daily life due to the initial adverse reaction experienced after drinking alcohol, and thus are protected against alcoholism.

Alcohol Drinking↗