Journal
DEVELOPMENTAL BRAIN RESEARCH
Volume 125, Issue 1-2, Pages 139-145Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0165-3806(00)00134-6
Keywords
brain development; alpha-ketoglutarate dehydrogenase complex; glucose oxidative metabolism; tricarboxylic acid cycle; thiamine-dependent enzyme
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Funding
- NICHD NIH HHS [P01 HD32573, P01 HD032573] Funding Source: Medline
- NINDS NIH HHS [R01 NS034813, R01 NS34813] Funding Source: Medline
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This study was initiated to test the hypothesis that the development of alpha -ketoglutarate dehydrogenase complex (KGDHC) activity, like that of pyruvate dehydrogenase complex, is one of the late developers of tricarboxylic acid (TCA) cycle enzymes. The postnatal development of KGDHC in rat brain exhibits four distinct region-specific patterns. The age-dependent increases in olfactory bulb (OB) and hypothalamus (HYP) form one pattern: low in postnatal days (P) 2 and 4, KGDHC activity rose linearly to attain adult level at P30. The increases in mid-brain (MB) and striatum (ST) constitute a second pattern: being < 40% of adult level at P2 and P4, KGDHC activity rose steeply between P10 and P17 and attained adult level by P30. The increases in cerebellum (CB), cerebral cortex (CC), and hippocampus (HIP) form a third pattern: being 25-30% of adult level at P2 and P4, KGDHC activity doubled between P10 and P17 and rose to adult level by P30. KGDHC activity development is unique in pens and medulla (PM): being > 60% of the adult level at P2, it rose rapidly to adult level by PIG. Thus, KGDHC activity develops earlier in phylogenetically older regions (PM) than in phylogenetically younger regions (CB, CC, HIP). Being lowest in activity among all TCA cycle enzymes, KGDHC activity in any region at any age will exert a limit on the maximum TCA cycle flux therein. The results may have functional and pathophysiological implications in control of brain glucose oxidative metabolism, energy metabolism, and neurotransmitter syntheses. (C) 2000 Elsevier Science B.V. All rights reserved.
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