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. Author manuscript; available in PMC: 2013 Jun 4.
Published in final edited form as: Mol Genet Metab. 2010 Jan 12;99(4):333–345. doi: 10.1016/j.ymgme.2009.12.007

Fig. 2.

Fig. 2

In brain, aKIC likely depletes glutamate through reverse transamination to leucine and alpha-ketoglutarate; this in turn affects brain content of GABA and glutamine (See Fig. 8). (A) In 1966, Prensky and Moser compared brain free amino acids from a 25 day-old infant who died in MSUD crisis (black bars) to a 4 day-old infant who did not have the disease (gray bars). They found profound depletion of glutamate, glutamine, and GABA in MSUD brain tissue (Ref. [15]). A similar phenomenon is observed in cultured astrocytes, Dbt−/− mice, and Poll-Hereford calves with MSUD (Refs. [12–14]). (B) The predominant effect of elevated aKIC in muscle may be to deplete alanine to form leucine and pyruvate. In a Mennonite child, plasma leucine (solid line) and alanine (dashed line) are reciprocally related over a 22-month period (rs = −0.86, p < 0.0001), suggesting this depletion mechanism operates in vivo (See Table 1).