Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a drug/fatty acid-activated trans cription factor involved in the starvation response, and is thus relevant to the ketogenic diet (KD). This article summarizes research indicating the role of PPAR alpha in central and peripheral nervous system function with particular reference to downstream targets relevant to anticonvulsant action.

Abstract: We report the isolation of cDNA clones encoding the somatic form of the E1α subunit of the pyruvate dehydrogenase complex of rat. The deduced amino acid sequence has 99.5, 98, and 97% identity, respectively, with the orthologous proteins of mouse, human, and pig and 98.5% identity with a rat E1α sequence reported previously. The cDNAs isolated in this and earlier studies predict different E1α subunit mRNA sizes and amino acid sequences. These differences have been investigated by PCR, northern blot hybridization, and RNase protection. We have used our E1α cDNA, in conjunction with cDNA probes to the E1β, E2, and E3 catalytic subunits of rat pyruvate dehydrogenase complex and also to rat citrate synthase, to perform RNase protection assays of developing rat whole brain RNA. The results show a 2.5‐fold increase in the concentration of each of the subunit mRNAs and a 1.2‐fold increase in citrate synthase mRNA from late foetal stage to 5 days post partum. Thereafter, the mRNA levels remained constant. These data indicate that the respective six‐and threefold increases in the amounts of pyruvate dehydrogenase complex and citrate synthase found to occur in rat brain between birth and adulthood are mediated principally by translational and/or posttranslational mechanisms.

We report the isolation of cDNA clones encoding the somatic form of the E1 alpha subunit of the pyruvate dehydrogenase complex of rat. The deduced amino acid sequence has 99.5, 98, and 97% identity, respectively, with the orthologous proteins of mouse, human, and pig and 98.5% identity with a rat E1 alpha sequence reported previously. The cDNAs isolated in this and earlier studies predict different E1 alpha subunit mRNA sizes and amino acid sequences. These differences have been investigated by PCR, northern blot hybridization, and RNase protection. We have used our E1 alpha cDNA, in conjunction with cDNA probes to the E1 beta, E2, and E3 catalytic subunits of rat pyruvate dehydrogenase complex and also to rat citrate synthase, to perform RNase protection assays of developing rat whole brain RNA. The results show a 2.5-fold increase in the concentration of each of the subunit mRNAs and a 1.2-fold increase in citrate synthase mRNA from late foetal stage to 5 days post partum. Thereafter, the mRNA levels remained constant. These data indicate that the respective six- and threefold increases in the amounts of pyruvate dehydrogenase complex and citrate synthase found to occur in rat brain between birth and adulthood are mediated principally by translational and/or posttranslational mechanisms.

cDNA clones encoding the testis-specific form of the rat pyruvate dehydrogenase complex E1 alpha subunit have been isolated. Comparison of the predicted amino acid sequence with those of the somatic and testis-specific E1 alpha forms of man and mouse and the somatic E1 alpha form of rat indicates the change of a serine residue, believed to be phosphorylated in vivo by pyruvate dehydrogenase E1 alpha-specific kinase, to an alanine at position 233. The implications of this change are discussed. Northern blot analysis and RNase protection assays indicate that the expression of mRNA encoding testis-specific E1 alpha subunit is restricted to testis whereas mRNA for the somatic form is found in all tissues analyzed, albeit in very small amounts in testis.

We analysed the structure of the white locus of Drosophila melanogaster in a family of related white mutants. The white-one mutant has bleach white eyes, and a Doc transposable element is inserted into the promoter region of the white locus. The DNA sequence of this Doc insertion was determined, and showed it to be closely related to other Drosophila melanogaster retroposons such as the I factor and the F, G and jockey elements. There are two long open reading frames, which encode a putative nucleic acid binding protein and a putative reverse transcriptase, respectively. Two independent, partially pigmented derivatives were analysed by cloning sequences from this region. In white-honey a transposable element of the retroviral class, B104, is inserted within the Doe element. In white-eosin there is an insertion within the Doc element of a 190 by sequence that appears to be a member of a novel family of transposable elements. This pogo element is of the same structural class as the Drosophila melanogaster P and hobo elements. These data are consistent with the hypothesis that the Doc retroposon cannot excise, and that, for the white-one mutation, flies with altered phenotypes are most often generated by the insertion of additional transposable elements.

DNA sequences from two spontaneous mutations of Drosophila melanogaster associated with insertion of a Doc transposable element have been cloned. In white-one, the element is inserted in the white locus close to where transcription initiates. In a lethal allele of suppressor of forked, su(f) S2 , the element is inserted within the transcription unit in the protein coding region. Four other Doc elements have been cloned from a wild-type strain. Doc is a member of the class of transposable elements known as retroposons, which includes the D. melanogaster F, G, Jockey, and I elements. There is no sequence homology between the ends of the Doc element. The 3′ or right end terminates with a polyadenylation signal sequence followed by a stretch of oligo-A. The length of the oligo-A varies between elements, and a duplication of variable size is found as a direct repeat flanking inserted Doc elements. Members of the family are conserved at the 3′ end, but may be truncated at the 5′ or left end. These structural features suggest a mechanism of transposition via an RNA intermediate.