Aldehyde dehydrogenase

About: Aldehyde dehydrogenase is a research topic. Over the lifetime, 3365 publications have been published within this topic receiving 107683 citations.

Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase.

Abstract: Human mitochondrial aldehyde dehydrogenase (ALDH-I) is potently, reversibly, and selectively inhibited by an isoflavone isolated from Radix puerariae and identified as daidzin, the 7-glucoside of 4',7-dihydroxyisoflavone. Kinetic analysis with formaldehyde as substrate reveals that daidzin inhibits ALDH-I competitively with respect to formaldehyde with a Ki of 40 nM, and uncompetitively with respect to the coenzyme NAD+. The human cytosolic aldehyde dehydrogenase isozyme (ALDH-II) is nearly 3 orders of magnitude less sensitive to daidzin inhibition. Daidzin does not inhibit human class I, II, or III alcohol dehydrogenases, nor does it have any significant effect on biological systems that are known to be affected by other isoflavones. Among more than 40 structurally related compounds surveyed, 12 inhibit ALDH-I, but only prunetin and 5-hydroxydaidzin (genistin) combine high selectivity and potency, although they are 7- to 15-fold less potent than daidzin. Structure-function relationships have established a basis for the design and synthesis of additional ALDH inhibitors that could both be yet more potent and specific.

Alcohol and aldehyde dehydrogenase.

Abstract: The enzymes mainly responsible for ethanol degradation in humans are liver alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH). Polymorphisms occur in both enzymes, with marked differences in the steady-state kinetic constants. The Km-values for ethanol of ADH isoenzymes relevant for alcohol degradation range from 49 microM to 36 microM, and the Vmax-values from 0.6 to 10 U/mg. Expression of an inactive form of the ALDH2 isoenzyme, the so-called Oriental variant, results in impaired acetaldehyde metabolizing capacity. The differences in ethanol and acetaldehyde metabolizing activities of allelic enzyme forms may be responsible in part for the large variation in the alcohol metabolism rate in humans. Interindividual differences in the isoenzyme pattern may contribute to the genetically determined predisposition for excessive alcohol intake.

Aldehyde dehydrogenase from human liver: primary structure of the cytoplasmic isoenzyme

Abstract: Analysis of CNBr fragments and other peptides from human liver cytoplasmic aldehyde dehydrogenase enabled determination of the complete primary structure of this protein The monomer has an acylated amino terminus and is composed of 500 amino acid residues, including 11 cysteine residues No evidence of any microheterogeneity was obtained, supporting the concept that the enzyme is a homotetramer The disulfiram-sensitive thiol in the protein, earlier identified through its reaction with iodoacetamide, is contributed by a cysteine residue at position 302, while the cysteine which in horse liver mitochondrial aldehyde dehydrogenase is reactive with coenzyme analogs appears to correspond to either Cys-455 or Cys-463 Analysis of glycine distribution and prediction of secondary structures to localize βαβ regions typical for coenzyme-binding are not fully unambiguous, but suggest a short region around position 245 as a likely segment for this function In this region, sequence similarities to parts of a bacterial aspartate-β-semialdehyde dehydrogenase and a mammalian alcohol dehydrogenase were noted Otherwise, no extensive similarities were detected in comparisons with characterized mammalian enzymes of similar activity or subunit size as aldehyde dehydrogenase (glyceraldehyde-3-phosphate dehydrogenase and glutamate dehydrogenase, respectively)