CIDeRplusGeneral Information:
| Id: | 3,503 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
| Mus musculus | |
| male | |
| PPARalpha-/- mouse | |
| article | |
| Reference: | Makowski L et al.(2009) Metabolic profiling of PPARalpha-/- mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation FASEB J. 23: 586-604 [PMID: 18945875] |
Interaction Information:
| Comment | Fasting glucose and ketone levels were lower, whereas plasma NEFAs were markedly elevated in PPARalpha -/- compared to PPARalpha+/+ mice. Plasma insulin levels and the insulin:glucose ratio in PPARalpha -/-mice trended lower in the fed state but was increased relative to wild-type mice in the fasted state. Thus, the absence of PPARalpha caused an inappropriate rise in insulin secretion during fasting-induced hypoglycemia. |
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Formal Description Interaction-ID: 32511 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Fasting glucose and ketone levels were lower, whereas plasma NEFAs were markedly elevated in PPARalpha -/- compared to PPARalpha+/+ mice. Plasma insulin levels and the insulin:glucose ratio in PPARalpha -/-mice trended lower in the fed state but was increased relative to wild-type mice in the fasted state. Thus, the absence of PPARalpha caused an inappropriate rise in insulin secretion during fasting-induced hypoglycemia. |
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Formal Description Interaction-ID: 32513 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In the fed state, most fatty acid-derived acylcarnitine species were present at similar levels in wild-type compared to the knockout mice. Notable exceptions included acetylcarnitine (C2) and beta-OH-butyrylcarnitine (C4OH, a strong marker of beta-oxidation and ketone metabolism), both of which were markedly decreased in plasma, liver, and skeletal muscle of PPARalpha -/- mice regardless of feeding status. Succinylcarnitine (C4DC), which arises from the TCA cycle intermediate succinyl-CoA, was reduced in plasma and liver of PPARalpha -/-mice, independent of condition. Skeletal muscle concentrations of this metabolite were also low in PPARalpha -/- compared to wild-type mice, but only in the fasted state. |
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Formal Description Interaction-ID: 32525 |
gene/protein affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In the fed state, most fatty acid-derived acylcarnitine species were present at similar levels in wild-type compared to the knockout mice. Notable exceptions included acetylcarnitine (C2) and beta-OH-butyrylcarnitine (C4OH, a strong marker of beta-oxidation and ketone metabolism), both of which were markedly decreased in plasma, liver, and skeletal muscle of PPARalpha -/- mice regardless of feeding status. Succinylcarnitine (C4DC), which arises from the TCA cycle intermediate succinyl-CoA, was reduced in plasma and liver of PPARalpha -/-mice, independent of condition. Skeletal muscle concentrations of this metabolite were also low in PPARalpha -/- compared to wild-type mice, but only in the fasted state. |
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Formal Description Interaction-ID: 32542 |
gene/protein affects_quantity of drug/chemical compound Hydroxybutyrylcarnitine |
| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In the fed state, most fatty acid-derived acylcarnitine species were present at similar levels in wild-type compared to the knockout mice. Notable exceptions included acetylcarnitine (C2) and beta-OH-butyrylcarnitine (C4OH, a strong marker of beta-oxidation and ketone metabolism), both of which were markedly decreased in plasma, liver, and skeletal muscle of PPARalpha -/- mice regardless of feeding status. Succinylcarnitine (C4DC), which arises from the TCA cycle intermediate succinyl-CoA, was reduced in plasma and liver of PPARalpha -/-mice, independent of condition. Skeletal muscle concentrations of this metabolite were also low in PPARalpha -/- compared to wild-type mice, but only in the fasted state. |
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Formal Description Interaction-ID: 32543 |
process affects_quantity of drug/chemical compound Hydroxybutyrylcarnitine |
| Comment | In the fed state, most fatty acid-derived acylcarnitine species were present at similar levels in wild-type compared to the knockout mice. Notable exceptions included acetylcarnitine (C2) and beta-OH-butyrylcarnitine (C4OH, a strong marker of beta-oxidation and ketone metabolism), both of which were markedly decreased in plasma, liver, and skeletal muscle of PPARalpha -/- mice regardless of feeding status. Succinylcarnitine (C4DC), which arises from the TCA cycle intermediate succinyl-CoA, was reduced in plasma and liver of PPARalpha -/-mice, independent of condition. Skeletal muscle concentrations of this metabolite were also low in PPARalpha -/- compared to wild-type mice, but only in the fasted state. |
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Formal Description Interaction-ID: 32544 |
affects_quantity of drug/chemical compound Hydroxybutyrylcarnitine |
| Comment | In the fed state, most fatty acid-derived acylcarnitine species were present at similar levels in wild-type compared to the knockout mice. Notable exceptions included acetylcarnitine (C2) and beta-OH-butyrylcarnitine (C4OH, a strong marker of beta-oxidation and ketone metabolism), both of which were markedly decreased in plasma, liver, and skeletal muscle of PPARalpha -/- mice regardless of feeding status. Succinylcarnitine (C4DC), which arises from the TCA cycle intermediate succinyl-CoA, was reduced in plasma and liver of PPARalpha -/-mice, independent of condition. Skeletal muscle concentrations of this metabolite were also low in PPARalpha -/- compared to wild-type mice, but only in the fasted state. |
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Formal Description Interaction-ID: 32545 |
gene/protein affects_quantity of drug/chemical compound Succinylcarnitine |
| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In the fed state, most fatty acid-derived acylcarnitine species were present at similar levels in wild-type compared to the knockout mice. Notable exceptions included acetylcarnitine (C2) and beta-OH-butyrylcarnitine (C4OH, a strong marker of beta-oxidation and ketone metabolism), both of which were markedly decreased in plasma, liver, and skeletal muscle of PPARalpha -/- mice regardless of feeding status. Succinylcarnitine (C4DC), which arises from the TCA cycle intermediate succinyl-CoA, was reduced in plasma and liver of PPARalpha -/-mice, independent of condition. Skeletal muscle concentrations of this metabolite were also low in PPARalpha -/- compared to wild-type mice, but only in the fasted state. |
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Formal Description Interaction-ID: 32547 |
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| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32548 |
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| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32549 |
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| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32551 |
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| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32552 |
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| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32553 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32554 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32555 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32557 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32559 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In wild-type mice, fasting-induced lipolysis was accompanied by increased plasma levels of several long-chain acylcarnitine species, including C16, C18:1, and C18:2. These same metabolites were elevated an additional 2- to 3-fold in PPARalpha -/- mice. Several of the hydroxylated acylcarnitine intermediates followed a similar pattern. Likewise, in the liver of PPARalpha -/- compared to wild-type mice, fasting levels of C16 and C18:1 were elevated, but medium-chain intermediates such as C8, C10, and C12 were present at lower levels. Skeletal muscle levels of C16, C18:1, and C18:2 were also elevated in fasted PPARalpha -/- mice, whereas the medium- and shorterchain species were either unchanged or decreased relative to their wild-type counterparts. This reciprocal long- to medium/short-chain acylcarnitine profile typically reflects a metabolic block that resides distal to carnitine palmitoyltransferase 1 (CPT1), the enzyme that synthesizes long-chain acylcarnitines and that functions as the first committed step in beta-oxidation. When long-chain products of this enzyme cannot be processed efficiently they accumulate within tissues and can be subsequently exported into the general circulation. |
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Formal Description Interaction-ID: 32560 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Also striking was the marked skeletal muscle accumulation of isovalerylcarnitine (C5), a byproduct of leucine catabolism. Whereas fasting did not alter C5 content in skeletal muscle of wild-type mice, this metabolite increased 5-fold in PPARalpha -/- animals. Pairwise correlation analysis revealed a strong positive relation between skeletal muscle C5 levels and plasma leucine/isoleucine, but only in PPARalpha -/- animals. Surprisingly, C5 levels were not elevated in the plasma of PPARalpha -/- mice, suggesting that tissue efflux of this specific metabolite might be limited for reasons that are yet unclear. |
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Formal Description Interaction-ID: 32561 |
gene/protein affects_quantity of drug/chemical compound Isovalerylcarnitine |
| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Also striking was the marked skeletal muscle accumulation of isovalerylcarnitine (C5), a byproduct of leucine catabolism. Whereas fasting did not alter C5 content in skeletal muscle of wild-type mice, this metabolite increased 5-fold in PPARalpha -/- animals. Pairwise correlation analysis revealed a strong positive relation between skeletal muscle C5 levels and plasma leucine/isoleucine, but only in PPARalpha -/- animals. Surprisingly, C5 levels were not elevated in the plasma of PPARalpha -/- mice, suggesting that tissue efflux of this specific metabolite might be limited for reasons that are yet unclear. |
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Formal Description Interaction-ID: 32563 |
gene/protein NOT affects_quantity of drug/chemical compound Isovalerylcarnitine |
| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In comparison to wild-type animals, free carnitine levels were dramatically reduced in plasma, muscle, and liver of PPARalpha -/- mice; this was apparent in both the fed and fasted states. |
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Formal Description Interaction-ID: 32564 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is a water-soluble quaternary amine that can be obtained from dietary sources and/or synthesized endogenously from trimethylated lysine residues derived from protein degradation. Because the liver is the principal site of carnitine biosynthesis, the hepatic expression of several carnitine regulatory genes was examined. Overnight fasting decreased mRNA abundance of trimethyllysine hydroxylase, epsilon (Tmlhe) and aldehyde dehydrogenase 9 family, and member A1, (Aldh9a1) in both genotypes. |
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Formal Description Interaction-ID: 32566 |
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| Drugbank entries | Show/Hide entries for TMLHE |
| Comment | Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is a water-soluble quaternary amine that can be obtained from dietary sources and/or synthesized endogenously from trimethylated lysine residues derived from protein degradation. Because the liver is the principal site of carnitine biosynthesis, the hepatic expression of several carnitine regulatory genes was examined. Overnight fasting decreased mRNA abundance of trimethyllysine hydroxylase, epsilon (Tmlhe) and aldehyde dehydrogenase 9 family, and member A1, (Aldh9a1) in both genotypes. |
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Formal Description Interaction-ID: 32567 |
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| Drugbank entries | Show/Hide entries for ALDH9A1 |
| Comment | Gene expression of gammabutyrobetaine hydroxylase 1 (Bbox1), a liver-specific enzyme that catalyzes the final and rate-limiting step in carnitine synthesis, was induced 30% on fasting in PPARalpha +/+ mice but suppressed 65% in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32568 |
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| Drugbank entries | Show/Hide entries for BBOX1 |
| Comment | Gene expression of gammabutyrobetaine hydroxylase 1 (Bbox1), a liver-specific enzyme that catalyzes the final and rate-limiting step in carnitine synthesis, was induced 30% on fasting in PPARalpha +/+ mice but suppressed 65% in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32569 |
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| Drugbank entries | Show/Hide entries for PPARA or BBOX1 |
| Comment | In both the fed and fasted states, expression of the carnitine/organic cation transporter (OCTN2 or SLC22A5) was reduced by 40% in PPARalpha -/- compared to PPARalpha +/+ mice. |
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Formal Description Interaction-ID: 32570 |
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| Drugbank entries | Show/Hide entries for PPARA or SLC22A5 |
| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32571 |
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| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32572 |
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| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32573 |
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| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32574 |
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| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32575 |
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| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32576 |
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| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32577 |
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| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32578 |
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| Drugbank entries | Show/Hide entries for |
| Comment | In liver of wild-type mice, the fasting-induced shift from glycolysis to gluconeogenesis was accompanied by a decrease in each of the organic acids measured, with the exception of alpha-ketoglutarate. |
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Formal Description Interaction-ID: 32579 |
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| Comment | In the absence of PPARalpha, hepatic citrate levels decreased, whereas fumarate and malate increased; these changes were detected as a main effect of genotype. |
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Formal Description Interaction-ID: 32581 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In the absence of PPARalpha, hepatic citrate levels decreased, whereas fumarate and malate increased; these changes were detected as a main effect of genotype. |
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Formal Description Interaction-ID: 32582 |
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| Drugbank entries | Show/Hide entries for PPARA or Fumarate |
| Comment | In the absence of PPARalpha, hepatic citrate levels decreased, whereas fumarate and malate increased; these changes were detected as a main effect of genotype. |
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Formal Description Interaction-ID: 32583 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | A striking interaction between genotype and feeding condition was observed for alpha-ketoglutarate, which fell robustly in liver of starved PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32584 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | The organic acid profile in the knockout animals is consistent with increased amino acid catabolism, as alpha-ketoglutarate functions as an amino group acceptor in multiple transamination reactions, whereas fumarate and malate are produced as intermediates of the urea cycle. |
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Formal Description Interaction-ID: 32585 |
affects_quantity of drug/chemical compound |
| Comment | The organic acid profile in the knockout animals is consistent with increased amino acid catabolism, as alpha-ketoglutarate functions as an amino group acceptor in multiple transamination reactions, whereas fumarate and malate are produced as intermediates of the urea cycle. |
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Formal Description Interaction-ID: 32586 |
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| Drugbank entries | Show/Hide entries for |
| Comment | The organic acid profile in the knockout animals is consistent with increased amino acid catabolism, as alpha-ketoglutarate functions as an amino group acceptor in multiple transamination reactions, whereas fumarate and malate are produced as intermediates of the urea cycle. |
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Formal Description Interaction-ID: 32587 |
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| Comment | In skeletal muscles of wild-type mice, lactate and citrate levels fell modestly during an overnight fast, whereas concentrations of other organic acid metabolites remained stable. |
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Formal Description Interaction-ID: 32588 |
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| Comment | In skeletal muscles of wild-type mice, lactate and citrate levels fell modestly during an overnight fast, whereas concentrations of other organic acid metabolites remained stable. |
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Formal Description Interaction-ID: 32589 |
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| Comment | In skeletal muscles of wild-type mice, lactate and citrate levels fell modestly during an overnight fast, whereas concentrations of other organic acid metabolites remained stable. |
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Formal Description Interaction-ID: 32590 |
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| Comment | In skeletal muscles of wild-type mice, lactate and citrate levels fell modestly during an overnight fast, whereas concentrations of other organic acid metabolites remained stable. |
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Formal Description Interaction-ID: 32591 |
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| Comment | In skeletal muscles of wild-type mice, lactate and citrate levels fell modestly during an overnight fast, whereas concentrations of other organic acid metabolites remained stable. |
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Formal Description Interaction-ID: 32593 |
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| Drugbank entries | Show/Hide entries for |
| Comment | In skeletal muscles of wild-type mice, lactate and citrate levels fell modestly during an overnight fast, whereas concentrations of other organic acid metabolites remained stable. |
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Formal Description Interaction-ID: 32594 |
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| Comment | Loss of PPARalpha resulted in reduced muscle levels of most organic acids. This was evident in the fed state and exacerbated by fasting, which caused a further drop in alpha-ketoglutarate, succinate, and fumarate, along with marginal declines in citrate and malate. |
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Formal Description Interaction-ID: 32595 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Loss of PPARalpha resulted in reduced muscle levels of most organic acids. This was evident in the fed state and exacerbated by fasting, which caused a further drop in alpha-ketoglutarate, succinate, and fumarate, along with marginal declines in citrate and malate. |
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Formal Description Interaction-ID: 32596 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Loss of PPARalpha resulted in reduced muscle levels of most organic acids. This was evident in the fed state and exacerbated by fasting, which caused a further drop in alpha-ketoglutarate, succinate, and fumarate, along with marginal declines in citrate and malate. |
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Formal Description Interaction-ID: 32597 |
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| Drugbank entries | Show/Hide entries for PPARA or Fumarate |
| Comment | Loss of PPARalpha resulted in reduced muscle levels of most organic acids. This was evident in the fed state and exacerbated by fasting, which caused a further drop in alpha-ketoglutarate, succinate, and fumarate, along with marginal declines in citrate and malate. |
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Formal Description Interaction-ID: 32598 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Loss of PPARalpha resulted in reduced muscle levels of most organic acids. This was evident in the fed state and exacerbated by fasting, which caused a further drop in alpha-ketoglutarate, succinate, and fumarate, along with marginal declines in citrate and malate. |
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Formal Description Interaction-ID: 32599 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Previous studies have shown that the muscle TCA cycle intermediate pool responds to changes in glucose availability and/or glycolytic activity. In agreement with these reports, fasted-state skeletal muscle content of alpha-ketoglutarate correlated strongly with blood glucose levels. Thus, the decrease in TCA cycle intermediates in muscle of the knockout mice might reflect a secondary consequence of hypoglycemia and/or glycogen depletion. |
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Formal Description Interaction-ID: 32600 |
phenotype affects_quantity of drug/chemical compound |
| Comment | In plasma of wild-type mice, fasting decreased alanine and aspartate and increased the branched chain amino acids (leucine, isoleucine, and valine), whereas most other amino acids remained relatively stable. |
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Formal Description Interaction-ID: 32601 |
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| Comment | In plasma of wild-type mice, fasting decreased alanine and aspartate and increased the branched chain amino acids (leucine, isoleucine, and valine), whereas most other amino acids remained relatively stable. |
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Formal Description Interaction-ID: 32602 |
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| Comment | In plasma of wild-type mice, fasting decreased alanine and aspartate and increased the branched chain amino acids (leucine, isoleucine, and valine), whereas most other amino acids remained relatively stable. |
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Formal Description Interaction-ID: 32603 |
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| Comment | In plasma of wild-type mice, fasting decreased alanine and aspartate and increased the branched chain amino acids (leucine, isoleucine, and valine), whereas most other amino acids remained relatively stable. |
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Formal Description Interaction-ID: 32604 |
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| Comment | In plasma of wild-type mice, fasting decreased alanine and aspartate and increased the branched chain amino acids (leucine, isoleucine, and valine), whereas most other amino acids remained relatively stable. |
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Formal Description Interaction-ID: 32605 |
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| Comment | In PPARalpha -/- mice, fasting caused a dramatic change in 10 of the 15 plasma analytes. Most notable were robust decreases in the gluconeogenic amino acid, alanine, and the ketogenic amino acid, tyrosine. |
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Formal Description Interaction-ID: 32606 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In PPARalpha -/- mice, fasting caused a dramatic change in 10 of the 15 plasma analytes. Most notable were robust decreases in the gluconeogenic amino acid, alanine, and the ketogenic amino acid, tyrosine. |
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Formal Description Interaction-ID: 32607 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In the liver, fasting led to a marked decrease in alanine, regardless of genotype, whereas glutamate/glutamine decreased only in the PPARalpha knockout mice. |
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Formal Description Interaction-ID: 32608 |
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| Comment | In the liver, fasting led to a marked decrease in alanine, regardless of genotype, whereas glutamate/glutamine decreased only in the PPARalpha knockout mice. |
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Formal Description Interaction-ID: 32609 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | In the liver, fasting led to a marked decrease in alanine, regardless of genotype, whereas glutamate/glutamine decreased only in the PPARalpha knockout mice. |
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Formal Description Interaction-ID: 32610 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Amino acids linked to the urea cycle (aspartate, arginine, and citrulline) were elevated in PPARalpha -/- compared to wild-type mice (detected as a main effect of genotype). |
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Formal Description Interaction-ID: 32612 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Amino acids linked to the urea cycle (aspartate, arginine, and citrulline) were elevated in PPARalpha -/- compared to wild-type mice (detected as a main effect of genotype). |
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Formal Description Interaction-ID: 32613 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Amino acids linked to the urea cycle (aspartate, arginine, and citrulline) were elevated in PPARalpha -/- compared to wild-type mice (detected as a main effect of genotype). |
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Formal Description Interaction-ID: 32614 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Taken together, the data suggest that impaired beta-oxidation in PPARalpha -/- mice leads to a compensatory increase in amino acid catabolism. |
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Formal Description Interaction-ID: 32615 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | Taken together, the data suggest that impaired beta-oxidation in PPARalpha -/- mice leads to a compensatory increase in amino acid catabolism. |
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Formal Description Interaction-ID: 32616 |
process incomplete fatty acid beta-oxidation increases_activity of |
| Comment | On the basis of the pronounced C5 peak the study evaluated skeletal muscle expression of isovaleryl-CoA dehydrogenase (IVD) and HMG-CoA lyase (HMGCL), mitochondrial enzymes required for leucine catabolism to acetyl-CoA. Consistent with the metabolite profiles, a starvation-induced increase in IVD expression was observed in the PPARalpha null mice but not in the wild-type controls. HMGCL was unaffected by genotype. |
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Formal Description Interaction-ID: 32617 |
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| Drugbank entries | Show/Hide entries for PPARA or IVD |
| Comment | On the basis of the pronounced C5 peak the study evaluated skeletal muscle expression of isovaleryl-CoA dehydrogenase (IVD) and HMG-CoA lyase (HMGCL), mitochondrial enzymes required for leucine catabolism to acetyl-CoA. Consistent with the metabolite profiles, a starvation-induced increase in IVD expression was observed in the PPARalpha null mice but not in the wild-type controls. HMGCL was unaffected by genotype. |
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Formal Description Interaction-ID: 32618 |
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| Drugbank entries | Show/Hide entries for IVD |
| Comment | On the basis of the pronounced C5 peak the study evaluated skeletal muscle expression of isovaleryl-CoA dehydrogenase (IVD) and HMG-CoA lyase (HMGCL), mitochondrial enzymes required for leucine catabolism to acetyl-CoA. Consistent with the metabolite profiles, a starvation-induced increase in IVD expression was observed in the PPARalpha null mice but not in the wild-type controls. HMGCL was unaffected by genotype. |
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Formal Description Interaction-ID: 32619 |
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| Drugbank entries | Show/Hide entries for HMGCL |
| Comment | On the basis of the pronounced C5 peak the study evaluated skeletal muscle expression of isovaleryl-CoA dehydrogenase (IVD) and HMG-CoA lyase (HMGCL), mitochondrial enzymes required for leucine catabolism to acetyl-CoA. Consistent with the metabolite profiles, a starvation-induced increase in IVD expression was observed in the PPARalpha null mice but not in the wild-type controls. HMGCL was unaffected by genotype. |
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Formal Description Interaction-ID: 32620 |
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| Drugbank entries | Show/Hide entries for PPARA or HMGCL |
| Comment | The study examined hepatic transamination capacity by measuring mRNA levels of the cytosolic and mitochondrial isoforms of glutamateoxaloacetate transaminase (GOT1 and GOT2, respectively) and tyrosine aminotransferase (TAT). In wildtype mice, expression of these genes was unaffected by fasting, implying a relatively low drive for amino acid catabolism. Conversely, in PPARalpha -/- mice, overnight fasting increased hepatic mRNA levels of GOT1 and TAT 3.2- and 4.4-fold, respectively, whereas expression of the mitochondrial GOT2 mRNA was unchanged. These results fit with the known roles of the GOT1 and TAT reactions in providing amino acid-derived carbon backbones for gluconeogenesis and ketogenesis, respectively, and might explain the marked fasting-induced depletion of alpha-ketoglutarate and tyrosine in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32621 |
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| Drugbank entries | Show/Hide entries for GOT1 |
| Comment | The study examined hepatic transamination capacity by measuring mRNA levels of the cytosolic and mitochondrial isoforms of glutamateoxaloacetate transaminase (GOT1 and GOT2, respectively) and tyrosine aminotransferase (TAT). In wildtype mice, expression of these genes was unaffected by fasting, implying a relatively low drive for amino acid catabolism. Conversely, in PPARalpha -/- mice, overnight fasting increased hepatic mRNA levels of GOT1 and TAT 3.2- and 4.4-fold, respectively, whereas expression of the mitochondrial GOT2 mRNA was unchanged. These results fit with the known roles of the GOT1 and TAT reactions in providing amino acid-derived carbon backbones for gluconeogenesis and ketogenesis, respectively, and might explain the marked fasting-induced depletion of alpha-ketoglutarate and tyrosine in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32622 |
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| Drugbank entries | Show/Hide entries for GOT2 |
| Comment | The study examined hepatic transamination capacity by measuring mRNA levels of the cytosolic and mitochondrial isoforms of glutamateoxaloacetate transaminase (GOT1 and GOT2, respectively) and tyrosine aminotransferase (TAT). In wildtype mice, expression of these genes was unaffected by fasting, implying a relatively low drive for amino acid catabolism. Conversely, in PPARalpha -/- mice, overnight fasting increased hepatic mRNA levels of GOT1 and TAT 3.2- and 4.4-fold, respectively, whereas expression of the mitochondrial GOT2 mRNA was unchanged. These results fit with the known roles of the GOT1 and TAT reactions in providing amino acid-derived carbon backbones for gluconeogenesis and ketogenesis, respectively, and might explain the marked fasting-induced depletion of alpha-ketoglutarate and tyrosine in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32623 |
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| Drugbank entries | Show/Hide entries for TAT |
| Comment | The study examined hepatic transamination capacity by measuring mRNA levels of the cytosolic and mitochondrial isoforms of glutamateoxaloacetate transaminase (GOT1 and GOT2, respectively) and tyrosine aminotransferase (TAT). In wildtype mice, expression of these genes was unaffected by fasting, implying a relatively low drive for amino acid catabolism. Conversely, in PPARalpha -/- mice, overnight fasting increased hepatic mRNA levels of GOT1 and TAT 3.2- and 4.4-fold, respectively, whereas expression of the mitochondrial GOT2 mRNA was unchanged. These results fit with the known roles of the GOT1 and TAT reactions in providing amino acid-derived carbon backbones for gluconeogenesis and ketogenesis, respectively, and might explain the marked fasting-induced depletion of alpha-ketoglutarate and tyrosine in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32624 |
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| Drugbank entries | Show/Hide entries for PPARA or GOT1 |
| Comment | The study examined hepatic transamination capacity by measuring mRNA levels of the cytosolic and mitochondrial isoforms of glutamateoxaloacetate transaminase (GOT1 and GOT2, respectively) and tyrosine aminotransferase (TAT). In wildtype mice, expression of these genes was unaffected by fasting, implying a relatively low drive for amino acid catabolism. Conversely, in PPARalpha -/- mice, overnight fasting increased hepatic mRNA levels of GOT1 and TAT 3.2- and 4.4-fold, respectively, whereas expression of the mitochondrial GOT2 mRNA was unchanged. These results fit with the known roles of the GOT1 and TAT reactions in providing amino acid-derived carbon backbones for gluconeogenesis and ketogenesis, respectively, and might explain the marked fasting-induced depletion of alpha-ketoglutarate and tyrosine in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32625 |
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| Drugbank entries | Show/Hide entries for PPARA or TAT |
| Comment | The study examined hepatic transamination capacity by measuring mRNA levels of the cytosolic and mitochondrial isoforms of glutamateoxaloacetate transaminase (GOT1 and GOT2, respectively) and tyrosine aminotransferase (TAT). In wildtype mice, expression of these genes was unaffected by fasting, implying a relatively low drive for amino acid catabolism. Conversely, in PPARalpha -/- mice, overnight fasting increased hepatic mRNA levels of GOT1 and TAT 3.2- and 4.4-fold, respectively, whereas expression of the mitochondrial GOT2 mRNA was unchanged. These results fit with the known roles of the GOT1 and TAT reactions in providing amino acid-derived carbon backbones for gluconeogenesis and ketogenesis, respectively, and might explain the marked fasting-induced depletion of alpha-ketoglutarate and tyrosine in PPARalpha -/- mice. |
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Formal Description Interaction-ID: 32626 |
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| Drugbank entries | Show/Hide entries for PPARA or GOT2 |
| Comment | PPARalpha -/- mice had 40-50% lower plasma and tissue levels of free carnitine, corresponding with diminished hepatic expression of genes involved in carnitine biosynthesis and transport. One week of oral carnitine supplementation conferred partial metabolic recovery in the PPARalpha(-/-) mice. |
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Formal Description Interaction-ID: 32627 |
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| Drugbank entries | Show/Hide entries for PPARA |
| Comment | PPARalpha -/- mice had 40-50% lower plasma and tissue levels of free carnitine, corresponding with diminished hepatic expression of genes involved in carnitine biosynthesis and transport. One week of oral carnitine supplementation conferred partial metabolic recovery in the PPARalpha(-/-) mice. |
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Formal Description Interaction-ID: 32628 |
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| Drugbank entries | Show/Hide entries for PPARA |