JCI - Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

William J. Zinnanti, Jelena Lazovic, Cathy Housman, Kathryn LaNoue, James P. O’Callaghan, Ian Simpson, Michael Woontner, Stephen I. Goodman, James R. Connor, Russell E. Jacobs, Keith C. Cheng

Published in Volume 117, Issue 11

J Clin Invest. 2007; 117(11):3258–3270 doi:10.1172/JCI31617

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Figure 5

Age-dependent brain biochemical changes with lysine diet exposure.

(A) Chromatogram of acyl-CoA esters from brain extract of weanling Gcdh^–/– mice on normal or lysine diet shows large accumulation of acetyl-CoA (†) and depletion of free CoA (‡) after 48 hours of lysine diet. Abs, absorbance. (B) Free CoA, acetyl-CoA, and glutaryl-CoA changes in brain extract of weanling and adult Gcdh^–/– mice and heterozygous controls on normal or lysine diets. Mean ± SEM, *P < 0.01; **P < 0.001. n = 6 each group. (C) ATP, phosphocreatine (PCr), and α-ketoglutarate changes in cortex of weanling and adult Gcdh^–/– mice and heterozygous controls on the lysine diet compared with normal diet. Mean ± SEM, ^ΧP < 0.04; ^ζP < 0.02. n = 4 each group. (D) Glutamate, glutamine, and GABA levels in weanling and adult Gcdh^–/– mice and heterozygous controls on the lysine diet compared with normal diet. Mean ± SEM. n = 6 each group.