Search results for PPARD

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Protein (1 results from a total of 1)

Identifier: R-HSA-446176
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: PPARD: Q03181

Interactor (1 results from a total of 1)

Identifier: Q03181-2
Species: Homo sapiens
Primary external reference: UniProt: Q03181-2

Reaction (4 results from a total of 4)

Identifier: R-HSA-5634100
Species: Homo sapiens
Compartment: nucleoplasm
In the nucleus, all-trans-retinoic acid (atRA), bounds to epidermal fatty acid-binding protein (FABP5), is transferred to the heterodimeric complex of retinoic acid receptor alpha RXRA) and peroxisome proliferator-activated receptor delta (PPARD). When bound to PPARD, atRA can significantly increase the expression of proteins involved in fatty acid oxidation and energy metabolism via its induction of PPARD (Wolf 2010, Amengual et al. 2012, Noy 2013).
Identifier: R-HSA-5422942
Species: Homo sapiens
Compartment: nucleoplasm
In the nucleus, all-trans-retinoic acid (atRA), bounds to epidermal fatty acid-binding protein (FABP5), is transferred to the heterodimeric complex of retinoic acid receptor alpha RXRA) and peroxisome proliferator-activated receptor delta (PPARD). When bound to PPARD, atRA can significantly increase the expression of proteins involved in fatty acid oxidation and energy metabolism via its induction of PPARD (Wolf 2010, Amengual et al. 2012, Noy 2013).
Identifier: R-HSA-200406
Species: Homo sapiens
Compartment: cytosol, mitochondrial outer membrane, mitochondrial intermembrane space
Carnitine palmitoyl transferase 1 (CPT1) associated with the inner mitochondrial membrane, catalyzes the reaction of palmitoyl-CoA (PALM-CoA) from the cytosol with carnitine (CAR) in the mitochondrial intermembrane space to form palmitoylcarnitine (L-PCARN) and CoA-SH. Three CPT1 isoforms exist; CPT1A, B and C. In the body, CPT1A is most abundant in liver while CPT1B is abundant in muscle. CPT1C is mainly expressed in neurons and localises to the ER and not to the mitochondria. It has little or no enzymatic activity in fatty acid oxidation. Both CPT1A and CPT1B are inhibited by malonyl-CoA (Morillas et al. 2002, 2004; Zammit et al. 2001; Zhu et al. 1997). Mutations in CPT1A are associated with defects in fatty acid metabolism and fasting intolerance, consistent with the role assigned to CPT1 from studies in vitro and in animal models (IJlst et al. 1998; Gobin et al. 2003).
In the nucleus, cellular retinoic acid-binding protein 1 or 2 (CRABP1 or 2), bound to all-trans-retinoic acid (atRA), directly binds to the heterodimeric complex of retinoic acid receptor alpha RXRA) and peroxisome proliferator-activated receptor delta (PPARD). When bound to PPARD, atRA can significantly increase the expression of proteins involved in fatty acid oxidation such as CPT1A via its induction of PPARD (Amengual et al. 2012).
Identifier: R-HSA-203946
Species: Homo sapiens
Compartment: mitochondrial matrix
In the nucleus, cellular retinoic acid-binding protein 1 or 2 (CRABP1 or 2), bound to all-trans-retinoic acid (atRA), directly binds to the heterodimeric complex of retinoic acid receptor alpha RXRA) and peroxisome proliferator-activated receptor delta (PPARD). When bound to PPARD, atRA can significantly increase the expression of proteins involved in energy metabolism such as PDK via induction of PPARD (Wolf 2010).
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 link glycolysis in the cytosol to the tricarboxylic acid cycle in the mitochondria matrix. In the mitochondrial matrix, Pyruvate Dehydrogenase Kinase (PDK) 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 isozymes 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 catalyze 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). The PDH-PDK axis is emerging as an important therapeutic point in genetic mitochondrial diseases, pulmonary arterial hypertension, and cancer, where cellular metabolism is perturbed (James et al. 2017). Dichloroacetate (DCA) is an acid salt analog of acetic acid used to inhibit PDK (Li et al. 2009). The effect is to keep the PDH complex active, thus stimulating mitochondrial oxidative metabolism. Chronic DCA administration may cause reversible peripheral neuropathy in adults (Kaufmann et al. 2006) but is well tolerated in children and adolescents suffering from the primary mitochondrial disease lactic acidosis (Abdelmalak et al. 2013, Stacpoole et al. 2008). The Warburg effect is the observation that cancer cells prefer aerobic glycolysis to oxidative phosphorylation (Warburg 1956). Whether this effect is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. It stands true for most types of cancer cells and has become one of the hallmarks of cancer. Aerobic glycolysis produces ATP at a much faster rate than oxidative phosphorylation, conferring growth advantages to tumor cells. DCA, binding to and inhibiting PDK isoforms, promotes a shift from glycolysis to oxidative phosphorylation and reverses the Warburg effect. Its potential role, alone or in combination, in several cancers is being investigated (Kankotia & Stacpoole, 2014, Tran et al., 2016; reviewed in Wang et al., 2021; Park et al., 2023).

Icon (1 results from a total of 1)

Species: Homo sapiens
Peroxisome proliferator-activated receptor delta
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