Dual relationships of xylitol and alcohol dehydrogenases in families of two protein types

Abstract

Xylitol dehydrogenase encoded by gene XYL2 from Pichia stipitis is a member of the medium‐chain alcohol dehydrogenase family, as evidenced by the domain organization and a distant homology (24% residue identity with the human class Iγ1 alcohol dehydrogenase). Much of a loop structure is missing, like in mammalian sorbitol and prokaryotic threonine dehydrogenases, many additional differences occur, and relationships are closest with the sorbitol dehydrogenase, the equivalence of which in P. stipitis may actually be the xylitol dehydrogenase. A second P. stipitis gene, also cloned and corresponding to a xylitol dehydrogenase, is highly different from XYL2, but encodes an enzyme with structural properties typical of the short‐chain dehydrogenase family, which also contains an alcohol dehydrogenase (from Drosophila). Thus, yeast xylitol dehydrogenases, like alcohol and polyol dehydrogenases from other sources, have dual derivations, combining similar enzyme activities in separate protein families. In contrast to the situation with the other enzymes, both forms of xylitol dehydrogenase are present in one organism.

Xylitol inhibits carcinogenic acetaldehyde production by Candida species

“…XDH belongs to the ADH enzyme family and the NAD-binding part of XDH resembles that of the liver ADH and other enzymes within the family. 13,20 Xylitol metabolism may also compete for the nicotinamide adenine dinucleotide (NADH) coenzyme leading to downregulation of ADH. Product inhibition and other regulatory circuits may also counter-regulate the ADH activity.…”

“…Xylitol is a five-carbon nonfermentable sugar alcohol which is metabolized into D-xylulose by xylitol dehydrogenase (XDH) closely resembling ADH. 13 Sugars are the main carbon and energy source for yeast cells but they can also use alternative nutrient sources such as amino acids and proteins. Different nutrients run through multiple metabolic pathways whose enzyme activities are regulated mainly by availability of oxygen and cellular coenzyme balance.…”

Fructose‐1,6‐bisphosphatase. Primary structure of the rabbit liver enzyme. ‘Intermediate’ variability of an oligomeric protein

“…There are no obvious segment patterns of variability among characterized bisphosphatases in contrast to those observed in the variable class I alcohol dehydrogenases [30], but there is an 8-residue segment at positions 118-125 which contains seven strictly conserved residues involved in metal and phosphate binding. However, the bisphosphatase family of enzymes resembles the medium-chain dehydrogenases (MDR) and the short-chain dehydrogenases (SDR) [31] with respect to conservation pattern for the different types of amino acid residues. In all cases, glycine is strongly over-represented among the conserved residues, 15 of 36 in MDR [31], 10 of 38 in SDR [31], and 9 of 34 in the bisphosphatases.…”

“…However, the bisphosphatase family of enzymes resembles the medium-chain dehydrogenases (MDR) and the short-chain dehydrogenases (SDR) [31] with respect to conservation pattern for the different types of amino acid residues. In all cases, glycine is strongly over-represented among the conserved residues, 15 of 36 in MDR [31], 10 of 38 in SDR [31], and 9 of 34 in the bisphosphatases. Thus, in contrast to previous suggestions, the rabbit liver fructose-l,6-bisphosphatase shows a variability pattern that is typical of other oligomeric families.…”

Ethanol utilization regulatory protein: Profile alignments give no evidence of origin through aldehyde and alcohol dehydrogenase gene fusion

“…We have used this approach to find evidence of relationships between aldehyde dehydrogenase (ALDH) and thiol proteases (Hempel et al, 1990), and between alcohol dehydrogenase (ADH) and a variety of other enzymes (Persson et al, 1993(Persson et al, , 1994Jornvall et al, 1995).…”