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Adenylate Kinase: A Ubiquitous Enzyme Correlated with Medical Conditions

  • Mihaela Ileana IonescuEmail author
Article
  • 72 Downloads

Abstract

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.

Keywords

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

Abbreviations

ADP

Adenosine diphosphate

AK

Adenylate kinase

AMP

Adenosine monophosphate

AMPK

AMP-activated protein kinases

Ap5A

P1,P5-di(adenosine-5′)pentaphosphate

ATP

Adenosine triphosphate

B4P

Bis(adenosine)-5′-tetraphosphate

BLAST

Basic local alignment search tool

BLOSUM

BLOcks SUbstitution Matrix

CDP

Cytidine diphosphate

dNTP

Deoxy-nucleoside triphosphates

DGYP

Aspartic acid glycine tyrosine proline

GTP

Guanosine triphosphate

hCINAP

Human coilin interacting nuclear ATPase protein

MGI

Mouse genomic informatics

MMAF

Multiple morphological abnormalities of the sperm flagella

NCBI

National Centre for Biotechnology Information

NTP

Nucleoside triphosphates

P-loop

Phosphate-binding loop

PCD

Primary ciliary dyskinesia

PDB

PROTEIN data bank

PRKACB

Protein kinase c-AMP activated catalytic subunit beta

RNAi

RNA-mediated interference

RNP

Ribonucleoprotein

SGK

Serine glycine lysine

UMP-CMP kinase

Uridine monophosphate-cytidine monophosphate kinase

Notes

Acknowledgements

This work is dedicated to the memory of Professor Dr. Octavian Bârzu, my mentor in the study of nucleoside monophosphate kinases. This work was supported by a grant of Ministery of Research and Innovation, CNCS - UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0016, within PNCDI III. The author would like to thank the referees for their generous and useful comments that have greatly improved the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that she has no conflicts of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Microbiology, Faculty of MedicineIuliu Haţieganu University of Medicine and PharmacyCluj-NapocaRomania
  2. 2.County Emergency Clinical HospitalCluj-NapocaRomania

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