4.2 Review

Adenylate Kinase: A Ubiquitous Enzyme Correlated with Medical Conditions

Journal

PROTEIN JOURNAL
Volume 38, Issue 2, Pages 120-133

Publisher

SPRINGER
DOI: 10.1007/s10930-019-09811-0

Keywords

Adenylate kinase; Nucleotide metabolism; Phosphotransfer enzymes; AMP-activated protein kinase; Adenine nucleotide; Homeostasis

Funding

  1. Ministery of Research and Innovation, CNCS - UEFISCDI, within PNCDI III [PN-III-P4-ID-PCCF-2016-0016]

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Adenylate kinase is a small, usually monomeric, enzyme found in every living thing due to its crucial role in energetic metabolism. This paper outlines the most relevant data about adenylate kinases isoforms, and the connection between dysregulation or mutation of human adenylate kinase and medical conditions. The following datadases were consulted: National Centre for Biotechnology Information, Protein Data Bank, and Mouse Genomic Informatics. The SmartBLAST tool, EMBOSS Needle Program, and Clustal Omega Program were used to analyze the best protein match, and to perform pairwise sequence alignment and multiple sequence alignment. Human adenylate kinase genes are located on different chromosomes, six of them being on the chromosomes 1 and 9. The adenylate kinases' intracellular localization and organ distribution explain their dysregulation in many diseases. The cytosolic isoenzyme 1 and the mitochondrial isoenzyme 2 are the main adenylate kinases that are integrated in the vast network of inflammatory modulators. The cytosolic isoenzyme 5 is correlated with limbic encephalitis and Leu673Pro mutation of the isoenzyme 7 leads to primary male infertility due to impairment of the ciliary function. The impairment of the mitochondrial isoenzymes 2 and 4 is demonstrated in neuroblastoma or glioma. The adenylate kinases are disease modifier that can assess the risk of diseases where oxidative stress plays a crucial role in pathogenesis like metabolic syndrome or neurodegenerative diseases. Because adenylate kinases has ATP as substrate, they are integrated in the global network of energetic process of any organism therefore are valid target for new pharmaceutical compounds.

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