Evolution Of Lactate Dehydrogenase Genes In Primates, With Special Consideration Of Nucleotide Organization In Mammalian Promoters
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چکیده
EVOLUTION OF LACTATE DEHYDROGENASE GENES IN PRIMATES, WITHSPECIAL CONSIDERATION OF NUCLEOTIDE ORGANIZATION INMAMMALIAN PROMOTERSbyZACK PAPPERAugust 2010Advisor: Dr. Derek E. WildmanMajor: Molecular Medicine and GeneticsDegree: Doctor of PhilosophyConcomitant with an increase in brain volume and mass, the allocation ofenergetic resources to the brain increased during stem anthropoid evolution,leading to humans. One mechanism by which this allocation may have occurredis through greater use of lactate as a neuronal fuel. Both the production oflactate, and conversion to pyruvate for use in aerobic metabolism, are catalyzed,in part, by the tetrameric enzyme lactate dehydrogenase (LDH). The two primaryLDH genes, LDHA and LDHB, confer different rates of substrate turnover to theLDH enzyme, and these rates lend to the argument that LDHA supportsanaerobic while LDHB supports aerobic metabolism. The expression profiles ofthese proteins shifted during primate evolution, with LDHA and LDHB the primaryLDH proteins expressed in strepsirrhine and anthropoid brains, respectively. Wedemonstrate that this expression shift does not coincide with changes to proteinstructure.
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