Methylthioadenosine phosphorylase activity in human erythrocytes

Area of Science:

• Biochemistry
• Human Physiology
• Enzymology

Background:

• 5 -methylthioadenosine is a byproduct of polyamine biosynthesis.
• Adenine is a crucial component of nucleic acids and energy carriers.
• Deficiency in adenine salvage pathways can lead to metabolic disorders.

Purpose of the Study:

• To identify and characterize an enzyme in human erythrocytes that degrades 5 -methylthioadenosine.
• To develop a rapid assay for quantifying 5 -methylthioadenosine phosphorylase activity.
• To investigate the role of this enzyme in purine metabolism, particularly in patients with adenine phosphoribosyltransferase deficiency.

Main Methods:

• High-performance liquid chromatography (HPLC) was used to develop a rapid assay for 5 -methylthioadenosine phosphorylase.
• Enzyme activity was measured in erythrocyte lysates from normal subjects and patients with purine metabolism disorders.
• A linked assay system was employed to assess the conversion of adenine to AMP.

Main Results:

• An enzyme, 5 -methylthioadenosine phosphorylase, capable of degrading 5 -methylthioadenosine to adenine was identified in human erythrocytes.
• The specific activity of this enzyme in normal subjects was determined to be 8.9 +/- 2.0 nmol . mg-1 Hb . h-1.
• Erythrocytes from patients with adenine phosphoribosyltransferase deficiency could not convert the produced adenine to AMP, unlike controls.

Conclusions:

• The identified enzyme plays a role in the catabolism of 5 -methylthioadenosine in human red blood cells.
• The findings support the hypothesis that endogenous adenine excretion in adenine phosphoribosyltransferase deficiency originates from 5 -methylthioadenosine, a byproduct of polyamine synthesis.
• This study provides insights into purine metabolism and its alterations in specific genetic disorders.