A genetic component in human lysosomal enzyme excretion.

Area of Science:

• Biochemistry
• Human Genetics
• Urology

Background:

• Acid hydrolases are abundant in human urine, originating from kidney proximal tubule epithelial cells.
• Urinary enzyme excretion is determined by lysosome secretion rate and enzyme concentration within lysosomes.
• Significant population variation exists for these excretion parameters.

Purpose of the Study:

• To investigate the heritability of urinary acid hydrolase excretion.
• To determine the genetic contribution to variations in lysosome composition and enzyme secretion.
• To assess the genetic basis of beta-glucuronidase excretion as a physiological marker.

Main Methods:

• Twin studies (monozygotic and dizygotic) were used to analyze variations in specific acid hydrolases.
• Enzyme levels (beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, alpha-galactosidase) in urine were quantified.
• Heritability of total enzyme excretion and lysosome composition was assessed.

Main Results:

• A substantial portion of the variation in urinary acid hydrolase excretion is genetically determined.
• Heritability was observed for both total enzyme excretion and lysosome composition.
• Findings suggest that the rate of lysosome secretion is also a heritable trait.

Conclusions:

• Urinary acid hydrolase excretion is a polygenic trait influenced by genetic factors.
• The heritability of beta-glucuronidase excretion is significant, impacting its use as a physiological indicator.
• Genetic control over lysosome composition and secretion rate underlies urinary enzyme profiles.