IDH - siesonline
IDH - siesonline
IDH - siesonline
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<strong>IDH</strong>1 and <strong>IDH</strong>2 mutations lead to “biochemical gain of function”<br />
• <strong>IDH</strong>, Isocitrate dehydrogenase (<strong>IDH</strong>1 =cytoplasmic; <strong>IDH</strong>2 = mitocondrial): NADPdependent<br />
enzyme that catalyze the oxidative decarboxilation of isocitrate to α-<br />
ketoglutarate, with concomitant production of NADPH.<br />
Isocitrate<br />
NADP<br />
<strong>IDH</strong>1<br />
<strong>IDH</strong>2<br />
NADPH<br />
α-ketoglutarate<br />
NADPH<br />
<strong>IDH</strong>1 R132<br />
<strong>IDH</strong>2 R172<br />
2-hydroxyglutarate<br />
NADP<br />
Mutated proteins harbour a new<br />
enzyma5c ac5vity: produc5on and<br />
accumula5on of 2HG,a rare metabolite<br />
normally present at very low levels in<br />
healthy cells<br />
Yan H et al. NEJM 2009; 360:765-9<br />
Gross S et al, JEM, 2010; 207:339
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