Intricate Regulation of Phosphoenolpyruvate Carboxykinase (PEPCK) Isoforms in Normal Physiology and Disease

Seenappa, Venu and Joshi, Manjunath B and Kapaettu, Satyamoorthy (2019) Intricate Regulation of Phosphoenolpyruvate Carboxykinase (PEPCK) Isoforms in Normal Physiology and Disease. Current Molecular Medicine, 19. pp. 1-26. ISSN 1566-5240

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Abstract

Background: The phosphoenolpyruvate carboxykinase (PEPCK) isoforms are considered as rate-limiting enzymes for gluconeogenesis and glyceroneogenesis pathways. PEPCK exhibits several interesting features such as a) organelle-specific isoforms (cytosolic and a mitochondrial) in vertebrate clade, b) tissue-specific expression of isoforms and c) organism- specific requirement of ATP or GTP as a cofactor. In higher organisms, PEPCK isoforms are intricately regulated and activated through several physiological and pathological stimuli such as corticoids, hormones, nutrient starvation and hypoxia. Isoform-specific transcriptional/translational regulation and their interplay in maintaining glucose homeostasis remain to be fully understood. Mounting evidence indicates the significant involvement of PEPCK isoforms in physiological processes (development and longevity) and in the progression of a variety of diseases (metabolic disorders, cancer, Smith–Magenis syndrome).Objective: The present systematic review aimed to assimilate existing knowledge of transcriptional and translational regulation of PEPCK isoforms derived from cell, animal and clinical models.Conclusion: Based on current knowledge and extensive bioinformatics analysis, in this review we have provided a comparative (epi) genetic understanding of PCK1 and PCK2 genes encompassing regulatory elements, disease-associated polymorphisms, copy number variations, regulatory miRNAs and CpG densities. We have also discussed various exogenous and endogenous modulators of PEPCK isoforms and their signaling mechanisms. A comprehensive review of existing knowledge of PEPCK regulation and function may enable identification of the underlying gaps to design new pharmacological strategies and interventions for the diseases associated with gluconeogenesis

Item Type: Article
Uncontrolled Keywords: CpG Methylation; SNP; Mutation; CNV; miRNA; Tumor; Hypoxia; AU elements
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 25 Sep 2019 10:05
Last Modified: 25 Sep 2019 10:05
URI: http://eprints.manipal.edu/id/eprint/154584

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