Journal article

Regulation of human 4-hydroxy-2-oxoglutarate aldolase by pyruvate and alpha-ketoglutarate: implications for primary hyperoxaluria type-3

Amadeus Huang, Julia Burke, Richard D Bunker, Yee-Foong Mok, Michael D Griffin, Edward N Baker, Kerry M Loomes

Biochemical Journal | PORTLAND PRESS LTD | Published : 2019

Abstract

4-hydroxy-2-oxoglutarate aldolase (HOGA1) is a mitochondrial enzyme that plays a gatekeeper role in hydroxyproline metabolism. Its loss of function in humans causes primary hyperoxaluria type 3 (PH3), a rare condition characterised by excessive production of oxalate. In this study, we investigated the significance of the associated oxaloacetate decarboxylase activity which is also catalysed by HOGA1. Kinetic studies using the recombinant human enzyme (hHOGA1) and active site mutants showed both these dual activities utilise the same catalytic machinery with micromolar substrate affinities suggesting that both are operative in vivo. Biophysical and structural studies showed that pyruvate was ..

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