Molecular genetic analysis of human alcohol dehydrogenase

Duester, Gregg; Hatfield, G. Wesley; Smith, Moyra

doi:10.1016/0741-8329(85)90015-1

Cited by 16 publications

(8 citation statements)

References 14 publications

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“…As mentioned before, sorbitol dehydrogenase has been ascribed to a single locus on chromosome 15 in man (191), and Class I alcohol dehydrogenases in man to loci on chromosome 4 (192). Such differences are compatible with close relationships because chromosomal organization is known to be little conserved between products of an ancestral gene duplication, as shown, for example, by the loci for a and p chains of hemoglobin (295).…”

mentioning

confidence: 59%

Sorbitol Dehydrogenase

Jeffery¹,

Jörnvall²

1988

Advances in Enzymology - And Related Areas of Molecular Biology

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confidence: 59%

Sorbitol Dehydrogenase

Jeffery¹,

Jörnvall²

1988

Advances in Enzymology - And Related Areas of Molecular Biology

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“…Comparison with the mouse suggests that the human ALDH genes are likely to be found on different chromosomes since genetic variants of mouse ' mitochondria1 ' and 'cytoplasmic ' aldehyde dehydrogenase isozymes have been used to map the loci (Ahd-1 and Ahd-2) to chromosomes 4 and 19 respectively (Holmes, 1978;Mather & Holmes, 1984;Holmes, Algar & Mather, 1985). This contrasts with the alcohol dehydrogenases where the mouse structural loci, Adh-1 and Adh-3, are both located on chromosome 3 (Holmes, Duley & Burnell, 1983) and four human loci, A D H l , ADH2, ADH3 and ADHS, are probably all on chromosome 4 Duester, Hatfield & Smith 1985). It is also interesting to note that the human formaldehyde dehydrogenase locus (FDH) has also been mapped to chromosome 4 ( Mecra Khan et al 1984).…”

Section: Discussionmentioning

confidence: 99%

Chromosome assignment, biochemical and immunological studies on a human aldehyde dehydrogenase, ALDH3

Santistéban

Povey

West

et al. 1985

Annals of Human Genetics

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The biochemical properties of ALDH isozymes have been examined in human tissues and one set, designated ALDH3, has been studied in detail. These components occur at highest levels in lung and stomach, but were not expressed in fetal tissues, or in blood, hair roots and fibroblasts. The ALDH3 isozymes show optimal activity with benzaldehyde and can use either NAD or NADP as cofactor. Antiserum against a partially purified ALDH3, from stomach, selectively precipitates this isozyme from human tissues and selectively recognizes an homologous component in the rat. Human and rodent ALDH3 were not immunoprecipitated by anti-ALDH1 or anti-ALDH2 antisera. High levels of expression were found in human-rodent hybrids, constructed using rat hepatoma cells, and these hybrids were used to assign the human ALDH3 gene to chromosome 17.

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“…This enzyme constitutes a complex system composed ofthree classes, I, II, III (20). The class I enzymes constitute the "typical" alcohol dehydrogenases composed of three types of subunit, a, 13, and -y, and originating from three loci (21) located on chromosome 4 (22).…”

mentioning

confidence: 99%

Mammalian alcohol dehydrogenases of separate classes: intermediates between different enzymes and intraclass isozymes.

Jörnvall¹,

Höög²,

Bahr‐Lindström³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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A comparison of the structure of class II human liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) (containing nT subunits) with those of the human class I isozymes (containing a, (3, and y subunits) reveals differences at about 40% of all positions. Variations are large for active-site regions, the segment around the second zinc atom, and for segments involved in subunit interactions. The two classes of alcohol dehydrogenase have diverged to exhibit structural differences to about half the extent of those between alcohol and polyol dehydrogenases. Hence, the two classes of alcohol dehydrogenase represent steps in enzyme rather than isozyme divergence. An evolutionary scheme that relates different types of zinc-containing mammalian dehydrogenases to one another encompasses at least three levels of gene duplication subsequent to the early step(s) of assembly of building unit(s). The first level of duplication results in the formation of now clearly different enzymes. The second level concerns the various classes of alcohol dehydrogenase, forming steps between typical enzymes and isozymes. The third level encompasses recent and multiple duplications in isozyme evolution of alcohol dehydrogenases. This scheme, linking zinc-containing dehydrogenases at different levels, resembles that in other protein families and reflects general patterns in protein relationships.Isozyme differences of mammalian alcohol dehydrogenases (alcohol:NAD' oxidoreductase, EC 1.1.1.1) were initially defined structurally for the horse liver enzyme (1). The enzyme from this source is still the only alcohol dehydrogenase for which the tertiary structure has been analyzed directly by x-ray crystallography (ref. 2; recent review in ref.3). However, progress in the knowledge of alcohol dehydrogenase in general has been rapid. The yeast, plant, and mammalian enzymes are related to the horse enzyme (4-16), all depending on functional zinc at the active site. A completely different type of alcohol dehydrogenase in insects has been differentiated in a scheme that separates alcohol dehydrogenases into two types that differ in zinc content, size, and enzymatic mechanisms (17). Furthermore, sorbitol dehydrogenases are known to be related to the group of large, zinc-containing alcohol dehydrogenases (17,18), while bacterial ribitol and glucose dehydrogenases are related to the line of small alcohol dehydrogenases that lack zinc (17,19).Knowledge about the human alcohol dehydrogenase has increased particularly rapidly. This enzyme constitutes a complex system composed ofthree classes, I, II, III (20). The class I enzymes constitute the "typical" alcohol dehydrogenases composed of three types of subunit, a, 13, and -y, and originating from three loci (21) located on chromosome 4 (22).All of these class I structures have been characterized (summaries in refs. 14 and 23) at both the protein and cDNA levels. Genomic structures (24) and their organizational relationships to other alcohol dehydrogenases (25) have also been studied. Fu...

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Molecular genetic analysis of human alcohol dehydrogenase

Cited by 16 publications

References 14 publications

Sorbitol Dehydrogenase

Sorbitol Dehydrogenase

Chromosome assignment, biochemical and immunological studies on a human aldehyde dehydrogenase, ALDH3

Mammalian alcohol dehydrogenases of separate classes: intermediates between different enzymes and intraclass isozymes.

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