Long-term regulation and promoter analysis of mammalian pyruvate dehydrogenase complex

Patel, Mulchand S.; Naik, Sharon; Johnson, Mark; Dey, R.

doi:10.1007/978-3-0348-8981-0_15

Cited by 5 publications

(4 citation statements)

References 59 publications

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“…For instance, total PDC activity in liver and adipose tissue increased by ϳ1.5-and 3.5-fold, respectively, in rats fed a high sucrose diet for 1-2 weeks compared with that of chow-fed controls [33]. The levels of the component proteins of PDC measured by immunological analysis in livers from high sucrose-fed animals closely correlated with changes in total PDC activity [34].…”

Section: Regulation Of Pdcmentioning

confidence: 83%

“…Interestingly, total and active PDC levels were not affected in heart and skeletal muscle of rats fed the high sucrose or high fat diets. Hypothyroidism in the rat caused about one-third reduction in total PDC activity in the liver, and this change was correlated with a similar reduction in amounts of E1 proteins (the other components of PDC were not measured) [33]. These stable changes in PDC activity are explained by long-term regulation occurring at the transcriptional level.…”

Section: Regulation Of Pdcmentioning

confidence: 85%

“…Gene organization and functional analysis of the promoter-regulatory regions of the three human PDC genes (E1␣, E1␤, and E3) and the mouse Pdha-2 gene have been reported [33]. Two genes have been found to encode the ␣ subunit of the E1 component of PDC in most mammals.…”

Section: Regulation Of Pdc Genesmentioning

confidence: 99%

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The biochemistry of the pyruvate dehydrogenase complex*

Patel

Korotchkina

2003

Biochem Molecular Bio Educ

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In the Westernized world the daily dietary caloric requirements are roughly provided as follows: 40% from carbohydrates, 40% from fats, and 20% from proteins. In some populations in developing countries the daily caloric contribution from carbohydrate is even higher due to its readily available sources and relatively low cost. Glucose, the principal product of carbohydrate digestion, passes through a series of enzymatic steps first in the non-oxidative glycolytic pathway (from glucose to pyruvate) followed by efficient oxidative metabolism via the tricarboxylic acid cycle (from acetyl-CoA to CO 2 and H 2 O) to harness a portion of its potential energy as ATP. Interestingly, these two major pathways are directly linked by the pyruvate dehydrogenase complex (PDC) 1 localized in the mitochondrial matrix (Fig. 1). In the fed state acetyl-CoA generated from pyruvate (derived mostly from glucose and some dietary amino acids) is also utilized for the biosynthesis of lipids such as long chain fatty acids and cholesterol by lipogenic tissues (such as liver and adipose tissues and under special conditions in mammary glands during lactation and in the brain during the prenatal and early postnatal development). Additionally, amino acids from excess dietary protein are metabolized by several specialized reactions or pathways generating intermediates that have to be ultimately converted to pyruvate first and then to acetylCoA via PDC either for complete oxidation to CO 2 and H 2 O or for lipogenesis. PDC is the only known reaction in most eukaryotes to generate acetyl-CoA (two-carbon compound) from pyruvate (three-carbon compound). Since this is a physiologically irreversible reaction and since there is no other known reaction or pathway to convert the two-carbon compound to pyruvate (or its equivalent) for the synthesis of glucose in animals, the flux through PDC is tightly regulated to meet the specific metabolic and energetic needs of different tissues during the fed and fasting (starvation) states. This is accomplished by covalent modification of the ratelimiting component of the complex involving sophisticated interplay among the components of the complex and allosteric modulations by acetyl-CoA and NADH, the products of the reaction (and also of fatty acid oxidation). It is evident from these simple considerations that PDC plays a key role as a gatekeeper of both caloric and glucose homeostasis in mammals. In this review, we will discuss recent developments concerning the structure-function relationship of this multienzyme complex from various organisms with emphasis on regulatory aspects of the mammalian complex. Detailed accounts of various aspects of this complex can be found in several excellent reviews [1][2][3][4][5][6][7][8][9][10][11]. STRUCTURE AND ORGANIZATION OF PDCPDC is present in most prokaryotic and eukaryotic organisms. It catalyzes several sequential reactions of oxidative decarboxylation of pyruvic acid by the action of its three catalytic components: (i) pyruvate dehydrogenase (E1) catalyzing the de...

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Section: Regulation Of Pdcmentioning

confidence: 83%

Section: Regulation Of Pdcmentioning

confidence: 85%

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The biochemistry of the pyruvate dehydrogenase complex*

Patel

Korotchkina

2003

Biochem Molecular Bio Educ

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“…La sous-unité E3 ou dihydrolipoyldéshydrogénase est un homodimère de 55 kDa qui fixe le FAD (flavine adénine dinucléotide). Ce complexe a été cloné, séquencé et localisé sur le chromosome 7 [2]. Enfin, la protéine X (51 kDa) porte un groupe lipoyl qui s'acétyle en présence de pyruvate ; bien que son rôle soit encore mal connu, elle pourrait intervenir dans le maintien de la cohésion du complexe en se liant aux sous-unités E2 et/ou E3.…”

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Le complexe pyruvate déshydrogénase : de l'organisation moléculaire à la pathologie.

Fouque¹,

Marsac²,

Benelli³

1998

Med Sci (Paris)

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Le complexe pyruvate déshydrogénase : de l'organisation moléculaire à la pathologie Le déficit en pyruvate déshydrogénase (PDH), décrit pour la première fois en 1970, est une maladie héréditaire du métabolisme intermédiaire affectant principalement le système nerveux. Plus d'une centaine d'observations en ont déjà été rapportées, mettant en évidence l'extrême hétérogénéité clinique et moléculaire de ce déficit. Cette hétérogénéité est liée à deux caractéristiques de la PDH : (1) sa structure caractérisée par l'assemblage de six sous-unités dont l'une est codée par un gène situé sur le chromosome X ; (2) son rôle dans le métabolisme du glucose et sa régulation, en particulier au niveau cérébral. La découverte d'un grand nombre de mutations différentes a conduit à mieux comprendre les mécanismes moléculaires complexes responsables de la diversité des tableaux cliniques observés dans les déficits en PDH.

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Lipoic Acid

Perham

2002

Encyclopedia of Molecular Biology

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Long-term regulation and promoter analysis of mammalian pyruvate dehydrogenase complex

Cited by 5 publications

References 59 publications

The biochemistry of the pyruvate dehydrogenase complex*

The biochemistry of the pyruvate dehydrogenase complex*

Le complexe pyruvate déshydrogénase : de l'organisation moléculaire à la pathologie.

Lipoic Acid

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