[Human adenylate kinases - classification, structure, physiological and pathological importance]

Area of Science:

• Biochemistry and Molecular Biology
• Enzymology
• Cellular Physiology

Background:

• Adenylate kinase (AK) is a ubiquitous phosphotransferase catalyzing reversible phosphate transfer between nucleotides.
• Human AKs exhibit conserved structural domains (CORE, NMPbd, NTPbd, LID) but diverse localizations.
• Nine human AK isoenzymes exist, with AK1 and AK2 showing highest affinity for adenine nucleotides.

Purpose of the Study:

• To summarize current knowledge on human adenylate kinase structure, properties, and functions.
• To explore the role of AKs in nucleotide homeostasis and cellular energy monitoring.
• To highlight the medical potential of AKs in disease diagnosis and treatment.

Main Methods:

• Analysis of amino acid sequence similarity to identify human AK isoenzymes.
• Review of existing literature on AK structure, function, and localization.
• Examination of genetic studies linking AK activity to disease etiology.

Main Results:

• Human AK isoenzymes are involved in nucleotide homeostasis and cellular energy charge monitoring.
• AKs participate in protein complexes, supplying substrates for channels, transporters, and P2 receptors.
• AK dysfunction is linked to diseases like aleukocytosis, hemolytic anemia, and primary ciliary dyskinesia (PCD).

Conclusions:

• Adenylate kinases play crucial roles in cellular differentiation, apoptosis, and oncogenesis.
• The involvement of AKs in various cellular processes and disease etiology underscores their diagnostic and therapeutic potential.
• Further research into human AKs can advance understanding and application in medicine.