Mitochondrial phosphoenolpyruvate carboxykinase deficiency

Clayton, Peter T.; Hyland, Keith; Brand, M.; Leonard, James V.

doi:10.1007/bf00441851

Cited by 45 publications

(15 citation statements)

References 20 publications

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“…In addition to PCK, gluconeogenesis is catalyzed by three other enzymes, pyruvate carboxylase, glucose‐6‐phosphatase and fructose‐1,6‐bisphosphatase, and is regulated by various other factors, such as insulin and glucagon . Patients congenitally deficient in PCK tend to show hypoglycemia and growth failure due to impaired gluconeogenesis . As none of the anti‐PCK2 positive AIH patients showed hypoglycemia and growth failure, it is unlikely that this antibody inhibits enzyme activity.…”

Section: Discussionsupporting

confidence: 50%

Anti‐phosphoenolpyruvate carboxykinase 2 antibody in patients with autoimmune hepatitis

Kanno

Watanabe

Takahashi

et al. 2014

Hepatology Research

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Section: Discussionsupporting

confidence: 50%

Anti‐phosphoenolpyruvate carboxykinase 2 antibody in patients with autoimmune hepatitis

Kanno

Watanabe

Takahashi

et al. 2014

Hepatology Research

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“…Meanwhile, Pck1, also known as phosphoenolpyruvate carboxykinase (PEPCK), encodes a rate-limiting enzyme for gluconeogenesis. PCK1 deficiency is lethal in both mice and humans [34,35]. However, liver hypertrophy and steatosis have been observed in liver-specific PCK1-deficient mice [34]; after 14 hours of fasting, such mice have a 71% increase in liver weight along with significant hepatic lipid accumulation.…”

Section: Resultsmentioning

confidence: 99%

PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

et al. 2007

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Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor α (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARα-induced liver hypertrophy is supported by their ability to predict non-PPARα–induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from siRNA-treated expression profiles. When combined with phenotypic evaluation, our approach should help to unleash the full potential of siRNAs in systematically unveiling the molecular mechanism of biological events.

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“…Very little is known about neuroimaging and histopathological findings. Astrocytosis of the cerebral cortex, basal ganglia and thalamus, in combination with small neuronal heterotopias in the cerebellar white matter and medulla, has been found in histopathological examination (Clayton et al 1986). Variable cerebral and cerebellar atrophy has been reported in MRI (Brismar and Ozand 1994).…”

Section: Gluconeogenesis Defectsmentioning

confidence: 98%

Magnetic resonance imaging in lactic acidosis

Knaap

Jakobs

Valk

1996

J of Inher Metab Disea

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Mitochondrial defects, defects in gluconeogenesis, and biotin-responsive multiple carboxylase deficiency are disorders characterized by primary lactic acidosis. In this review, characteristic findings in magnetic resonance imaging (MRI) of the brain, as related to histopathological abnormalities, are described for the different disorders and the diagnostic value of the MRI findings is discussed. Inborn errors of metabolism with primary lactic acidosis should be considered in particular when MRI shows lesions similar to or reminiscent of effects of focal or generalized hypoxia-ischaemia, or when MRI shows signs of chronic neurodegeneration, but rarely in cases with predominantly white-matter changes.

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Mitochondrial phosphoenolpyruvate carboxykinase deficiency

Cited by 45 publications

References 20 publications

Anti‐phosphoenolpyruvate carboxykinase 2 antibody in patients with autoimmune hepatitis

Anti‐phosphoenolpyruvate carboxykinase 2 antibody in patients with autoimmune hepatitis

PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

Magnetic resonance imaging in lactic acidosis

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