Adenylate kinases in man: evidence for a third locus

Area of Science:

• Biochemistry
• Human Genetics
• Enzymology

Background:

• Adenylate kinase (AK) isozymes play crucial roles in cellular energy metabolism.
• Understanding the genetic basis and tissue distribution of AK isozymes is essential for comprehending their physiological functions.

Purpose of the Study:

• To characterize the tissue distribution and properties of human adenylate kinase isozymes.
• To identify and provisionally designate a third AK isozyme locus (AK3) and investigate its genetic linkage.

Main Methods:

• Examination of adenylate kinase isozyme activity across various human tissues using different substrates.
• Analysis of electrophoretic mobility, molecular size, and inhibitor resistance of identified isozymes.
• Somatic cell hybrid studies to determine the chromosomal location (synteny) of the AK3 locus.

Main Results:

• Identification of isozymes linked to AK1 and AK2 loci, and a novel set of isozymes attributed to the AK3 locus.
• AK3 isozymes demonstrate specific activity with GTP + AMP or ITP + AMP, differing from AK1 and AK2.
• AK3 isozymes exhibit distinct electrophoretic mobility and silver inhibition resistance compared to AK1 and AK2.
• Somatic cell hybrid data suggest AK3 is not syntenic with AK2 (chromosome 1) but is likely syntenic with AK1 on chromosome 9.

Conclusions:

• A third human adenylate kinase locus, AK3, has been identified, likely encoding nucleosidetriphosphate-adenylate kinase (2.7.4.10).
• The AK3 locus is provisionally mapped to chromosome 9, distinct from the AK2 locus on chromosome 1.
• Further studies are needed to explore the functional significance and potential genetic variations of the AK3 locus.