Search results for PDK4

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Species

Types

Compartments

Reaction types

Search properties

Protein (1 results from a total of 1)

Identifier: R-HSA-203941
Species: Homo sapiens
Compartment: mitochondrial matrix
Primary external reference: UniProt: PDK4: Q16654

Reaction (1 results from a total of 1)

Identifier: R-HSA-203946
Species: Homo sapiens
Compartment: mitochondrial matrix
The mitochondrial pyruvate dehydrogenase (PDH) complex (lipo-PDH) irreversibly decarboxylates pyruvate to acetyl CoA, thereby serving to oxidatively remove lactate, which is in equilibrium with pyruvate, and to link glycolysis in the cytosol to the tricarboxylic acid cycle in the mitochondria matrix. Pyruvate Dehydrogenase Kinase (PDK) in the mitochondrial matrix catalyzes the phosphorylation of serine residues of the E1 alpha subunit of the PDH complex, inactivating it. Pyruvate negatively regulates this reaction, and NADH and acetyl CoA positively regulate it (Bao et al. 2004). Four PDK isoforms have been identified and shown to catalyze the phosphorylation of E1 alpha in vitro (Gudi et al. 1995, Kolobova et al. 2001, Rowles et al. 1996). They differ in their expression patterns and quantitative responses to regulatory small molecules. All four isoforms catalyze the phosphorylation of serine residues 293 ("site 1") and 300 ("site 2"); PDK1 can also catalyse the phosphorylation of serine 232 ("site 3"). Phosphorylation of a single site in a single E1 alpha subunit is sufficient for enzyme inactivation (Bowker-Kinley et al. 1998, Gudi et al. 1995, Kolobova et al. 2001, Korotchkina and Patel, 2001).

Pathway (1 results from a total of 1)

Identifier: R-HSA-1989781
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane, extracellular region, lipid droplet, mitochondrial inner membrane, mitochondrial matrix, mitochondrial outer membrane, nucleoplasm, peroxisomal matrix, peroxisomal membrane, plasma membrane
The set of genes regulated by PPAR-alpha is not fully known in humans, however many examples have been found in mice. Genes directly activated by PPAR-alpha contain peroxisome proliferator receptor elements (PPREs) in their promoters and include:
1) genes involved in fatty acid oxidation and ketogenesis (Acox1, Cyp4a, Acadm, Hmgcs2);
2) genes involved in fatty acid transport (Cd36, , Slc27a1, Fabp1, Cpt1a, Cpt2);
3) genes involved in producing fatty acids and very low density lipoproteins (Me1, Scd1);
4) genes encoding apolipoproteins (Apoa1, Apoa2, Apoa5);
5) genes involved in triglyceride clearance ( Angptl4);
6) genes involved in glycerol metabolism (Gpd1 in mouse);
7) genes involved in glucose metabolism (Pdk4);
8) genes involved in peroxisome proliferation (Pex11a);
9) genes involved in lipid storage (Plin, Adfp).
Many other genes are known to be regulated by PPAR-alpha but whether their regulation is direct or indirect remains to be found. These genes include: ACACA, FAS, SREBP1, FADS1, DGAT1, ABCA1, PLTP, ABCB4, UGT2B4, SULT2A1, Pnpla2, Acsl1, Slc27a4, many Acot genes, and others (reviewed in Rakhshandehroo et al. 2010).
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