KIAA0089: Human glycerol 3 phosphate dehydrogenase like enzyme
PDB Code: 2PLA
The structure of a functionally uncharacterized human gene product, which is highly expressed in skeletal muscle, was determined. The protein shows high similarity to previously determined glycerol 3 phosphate dehydrogenases.
It is likely that KIAA0089 is part of the glycerol 3 phosphate shuttle operative in skeletal muscle tissue. This pathway ensures regeneration of cytosolic NAD+ from NADH formed during glycolysis. This NAD+ regeneration is necessary for glycolysis to proceed. Since cytosolic NADH cannot enter mitochondria itself, the other product of the reaction, glycerol 3 phosphate, crosses the mitochondrial membrane. Accordingly, in this pathway a cytosolic dehydrogenase (presumably KIAA0089) reduces dihydroxyacetone phosphate in an NADH dependent reaction to yield glycerol 3 phosphate and NAD+. Glycerol 3 phosphate enters mitochondria and is oxidized by an FAD dependent enzyme to dihydroxyacetone phosphate and FADH2 which is then utilized to generate ATP. Thus the initial electrons from cytosolic NADH are transported into mitochondria and further funneled into the respiratory chain by a shuttle system that utilizes two subcellularly differentially localized oxidoreductases that interconvert dihydroxyacetone phosphate and glycerol 3 phosphate.
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