Alcohol dehydrogenase 1B is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''ADH1B''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
The protein encoded by this gene is a member of the
alcohol dehydrogenase
Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NA ...
family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol (beverage alcohol),
retinol
Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family found in food and used as a dietary supplement. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xeroph ...
, other aliphatic alcohols,
hydroxysteroids, and
lipid peroxidation
Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chai ...
products. The encoded protein, known as ADH1B or beta-ADH, can form homodimers and heterodimers with ADH1A and ADH1C subunits, exhibits high activity for
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
oxidation and plays a major role in ethanol catabolism (oxidizing ethanol into acetaldehyde). The acetaldehyde is further metabolized to acetate by
aldehyde dehydrogenase
Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...
genes. Three genes encoding the closely related alpha, beta and gamma subunits are tandemly organized in a genomic segment as a
gene cluster
A gene family is a set of homologous genes within one organism. A gene cluster is a group of two or more genes found within an organism's DNA that encode similar polypeptides, or proteins, which collectively share a generalized function and are ...
.
The human gene is located on
chromosome 4
Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 186 million base pairs (the building material of DNA) and represents between 6 and 6.5 percent of the t ...
in 4q22.
Previously ''ADH1B'' was called ''ADH2''. There are more genes in the family of alcohol dehydrogenase. These genes are now referred to as ''
ADH1A'', ''
ADH1C
Alcohol dehydrogenase 1C is an enzyme that in humans is encoded by the ''ADH1C'' gene.
Function
This gene encodes class I alcohol dehydrogenase
Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organi ...
'', and ''
ADH4'', ''
ADH5
Alcohol dehydrogenase class-3 is an enzyme that in humans is encoded by the ''ADH5'' gene.
This gene encodes glutathione-dependent formaldehyde dehydrogenase or the class III alcohol dehydrogenase chi subunit, which is a member of the Alcohol (ch ...
'', ''
ADH6
Alcohol dehydrogenase 6 is an enzyme that in humans is encoded by the ''ADH6'' gene.
This gene encodes class V alcohol dehydrogenase, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of subs ...
'' and ''
ADH7
Alcohol dehydrogenase class 4 mu/sigma chain is an enzyme that in humans is encoded by the ''ADH7'' gene.
Function
This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, which is a member of the alcohol dehydrogenase family. M ...
''.
Variants
A
single nucleotide polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
(SNP) in ''ADH1B'' i
rs1229984 that changes
arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
to
histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...
at
residue 47 of the mature protein; standard nomenclature now includes the initiating methionine, so the position is officially 48. The 'typical' variant of this has been referred to as ADH2(1) or ADH2*1 while the 'atypical' has been referred to as, e.g., ADH2(2), ADH2*2, ADH1B*48His. This SNP is associated with the risk for alcohol dependence, alcohol use disorders and alcohol consumption, with the atypical genotype having reduced risk of
alcoholism
Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
. The atypical genotype produces a more active enzyme and is associated with
rice domestication.
Another SNP is rs2066702
rg370Cys originally called position 369. This SNP is at high frequencies in populations from Africa, and also reduces risk for alcohol dependence.
Role in pathology
A marked decrease of ADH1B
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
was detected in corneal
fibroblast
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
s taken from persons suffering from
keratoconus
Keratoconus (KC) is a disorder of the eye that results in progressive thinning of the cornea. This may result in blurry vision, double vision, nearsightedness, irregular astigmatism, and light sensitivity leading to poor quality-of-life. ...
.
See also
*
Alcohol dehydrogenase
Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NA ...
*
Aldehyde dehydrogenase
Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...
References
Further reading
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External links
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{{PDB Gallery, geneid=125