enzymology An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

, a D-xylulose reductase ( EC 1.1.1.9) is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that is classified as an

Oxidoreductase In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ut ...

(EC 1) specifically acting on the CH-OH group of donors (EC 1.1.1) that uses NAD⁺ or NADP⁺ as an acceptor (EC 1.1.1.9). This enzyme participates in pentose and glucuronate interconversions; a set of metabolic pathways that involve converting

pentose In chemistry, a pentose is a monosaccharide (simple sugar) with five carbon atoms. The chemical formula of many pentoses is , and their molecular weight is 150.13 g/mol.glucuronate into other compounds.

Nomenclature

The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivi ...

of this enzyme class is xylitol:NAD⁺ 2-oxidoreductase (D-xylulose-forming). Other common names used include : * NAD⁺-dependent xylitol dehydrogenase * xylitol dehydrogenase* erythritol dehydrogenase (as this enzyme also acts as an L-erythrylose reductase) * 2,3-cis-polyol(DPN) dehydrogenase (C3-5) * pentitol-DPN dehydrogenase, and * xylitol-2-dehydrogenase

EC number

An Enzyme Commission (EC) number is a classification identifier given to all enzymes that helps identify their function and relationships to other enzymes. The EC number for D-xylulose reductase is 1.1.1.9, the breakdown is as follows: * EC 1: Oxidoreductase enzymes * EC 1.1.1: An oxidoreductase enzyme that acts on CH-OH group of donors * EC 1.1.1.9: An oxidoreductase enzyme that acts on the CH-OH group of donors that uses NAD+ or NADP+ as an acceptor

Catalyzed reaction

D-xylulose reductase catalyzes the chemical reaction xylitol + NAD⁺ ⇌ D-xylulose + NADH + H⁺ where

xylitol Xylitol is a chemical compound with the formula , or HO(CH2)(CHOH)3(CH2)OH; specifically, one particular Stereoisomerism, stereoisomer with that structural formula. It is a colorless or white crystalline solid. It is classified as a polyalcoho ...

and NAD are the substrates and D-xylulose, NADH and H⁺ are the products. NAD⁺ acts as the

coenzyme A cofactor is a non-protein chemical compound or Metal ions in aqueous solution, metallic ion that is required for an enzyme's role as a catalysis, catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can ...

for the chemical reaction. The enzyme is a part of a class called short-chain dehydrogenase/reductases (SDRs) enzyme class which are catalyzed by the amino acid tyrosine which acts as an acid or base. Additionally, hydrogen bonding within the enzyme is thought to help with catalysis by changing the surrounding environment to be favorable towards the reaction.

Role in metabolism

In cellular metabolism D-xylulose reductase is essential in various organisms. In bacteria, D-xylulose reductase is the second step of D-xylose metabolism which is necessary cellular growth. First, D-xylose is converted to xylitol which then is converted to D-xylulose when D-xylulose reductase exchanges NAD⁺ for NADH. D-xylulose then becomes phosphorylated, and proceeds through the rest of the cycle to create α-ketoglutarate which eventually enters the

TCA cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

for energy production.

Species distribution

D-xylulose reductase is found in both prokaryotes and eukaryotes; including molds, yeasts, and fungi.

Structure

Only one structure has been solved for this enzyme, under th
Protein Data Bank
accession cod
1ZEM
The enzyme has 262 amino acid residues and is a

tetramer A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula ...

. Each monomer has a Rossman fold domain made up of seven β sheets side by side with three short α helices on one end of the sheet and three longer α helices on the other. There are two shorter helices that stay outside of this Rossman fold. The N-terminal region of the primary sequence has been found to be responsible for the selectivity of binding NAD⁺, and the active site is located between helices αFG1, αFG2 and the C-terminal end of the β sheet. Some images of D-xylulose reductase show magnesium bound, this is because the solution used to grow the protein crystals for visualization that were used contained 100mM of MgCl₂. However it has been found that D-xylulose reductase is not inhibited by magnesium; it has even been suggested that magnesium may be important for stabilization and formation of the oligomers.

Function

One example of a mold that uses the enzyme is ''Aspergillus carbonarius;'' where the enzyme creates an intermediate for the

pentose phosphate pathway The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt or HMP shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (five-carbon sugars) as well as ribose 5-ph ...

. D-xylose is converted to xylitol by xylose reductase, then xylitol is converted to xylulose by D-xylulose reductase, afterwards xylulose is converted to xylulose-5-phosphate by xylulokinase and xylulose-5-P then goes into the pentose phosphate pathway for energy and intermediates production. In yeast, such as ''

Hansenula polymorpha ''Ogataea polymorpha'' is a methylotrophic yeast with unusual characteristics. It is used as a protein factory for pharmaceuticals. ''Ogataea polymorpha'' belongs to a limited number of methylotrophic yeast species – yeasts that can grow on ...

'' d-xylulose reductase has been found to help ferment xylose into ethanol, however it usually results in an accumulation of xylitol due to the imbalance between cofactor preferences in xylose reductase and xylulose reductase. In fungi d-xylulose reductase also ferments xylose into ethanol as a result of metabolic conditions (such as anaerobic conditions).