Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle.

ABSTRACT: Here we describe two families with retinitis pigmentosa, a hereditary neurodegeneration of rod and cone photoreceptors in the retina. Affected family members were homozygous for loss-of-function mutations in IDH3B, encoding the beta-subunit of NAD-specific isocitrate dehydrogenase (NAD-IDH, or IDH3), which is believed to catalyze the oxidation of isocitrate to alpha-ketoglutarate in the citric acid cycle. Cells from affected individuals had a substantial reduction of NAD-IDH activity, with about a 300-fold increase in the K(m) for NAD. NADP-specific isocitrate dehydrogenase (NADP-IDH, or IDH2), an enzyme that catalyzes the same reaction, was normal in affected individuals, and they had no health problems associated with the enzyme deficiency except for retinitis pigmentosa. These findings

SUBMITTER: Hartong DT 

PROVIDER: S-EPMC2596605 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature