A metabolic bypass of the triosephosphate isomerase reaction.
Triosephosphate isomerase (TIM) catalyzes the interconversion of d-glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, an essential step in glycolytic and gluconeogenic metabolism. To uncover promiscuous isomerases embedded within the Escherichia coli genome, we searched for genes capable of restoring growth of a TIM-deficient bacterium under gluconeogenic conditions. Rather than discovering an isomerase, we selected yghZ, a gene encoding a member of the aldo-keto reductase superfamily. Here we show that YghZ catalyzes the stereospecific, NADPH-dependent reduction of l-glyceraldehyde 3-phosphate, the enantiomer of the TIM substrate. This transformation provides an alternate pathway to the formation of dihydroxyacetone phosphate.
Desai
Kevin K
KK
Department of Chemistry and Biochemistry, 217 Dittmer Laboratory of Chemistry, Florida State University, Tallahassee, Florida 32306-4390, USA.
Miller
Brian G
BG
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D002384:Catalysis; D004099:Dihydroxyacetone Phosphate / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005986:Glyceraldehyde 3-Phosphate / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D013237:Stereoisomerism; D013379:Substrate Specificity; D013403:Sugar Phosphates / Q000737:chemistry / Q000378:metabolism*; D014305:Triose-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism*; D014306:Trioses / Q000378:metabolism
D029968:Escherichia coli Proteins; D013403:Sugar Phosphates; D014306:Trioses; D005986:Glyceraldehyde 3-Phosphate; D004099:Dihydroxyacetone Phosphate; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D014305:Triose-Phosphate Isomerase