A genetic component in human lysosomal enzyme excretion

Abstract

Acid hydrolases are present in normal human urine in appreciable amounts. Their source appears to be lysosomes released by kidney proximal tubule epithelial cells. For a given lysosomal enzyme the total amount excreted is the product of two parameters, a general one describing the rate of lysosome secretion and a specific one describing the relative concentration of that enzyme in lysosomes. There is considerable population variation in both parameters. Studies of beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, and alpha-galactosidase in monozygotic and dizygotic twins show that an appreciable part of this variation is genetic in origin. This appears to be true for both total enzyme excretion and lysosome composition. Although it was not possible to test directly whether this is also true for the rate of lysosome secretion, the fact that the two former parameters are both heritable strongly suggests that the rate of lysosome excretion is also a heritable trait. Taken together with previous data, the results suggest polygenic control of these biochemical traits. It is particularly significant that beta-glucuronidase excretion in normal individuals is a heritable trait since the excretion of this enzyme has frequently been used as a measure of normal and pathological physiological changes.

Non-invasive high-risk screening for Fabry disease hemizygotes and heterozygotes

“…It is known that circulating low-molecular weight proteins, such as α-gal A, are filtered by the glomerulus, taken up by the tubular epithelium, and excreted in the urine [42]. Therefore, the concentration of urinary α-gal A may not only depend on the α-gal A level in plasma or kidney tissue, but also on glomerular filtration rate (GFR), tubular function, endocytotic processes in the tubular epithelium, and other factors [43][44][45]. Such phenomena may be responsible for the above results.…”

Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring.

“…The chemical synthesis of the N-glucuronide of MbOCA was based on a modification" of the method of Boyland et al '3 MbOCA (10 mM in ethanol) was mixed with an equal volume of glucuronic acid sodium salt (20 mM in sodium phosphate buffer 0-1 M, pH 71) and the mixture left in the dark at 0-4°C for 16 High performance liquid chromatography (HPLC) purification of the N-glucuronides of MbOCA was achieved using a Nova Pak 5 ,um column 10 cm x 8 mm (Waters Radial Pak) with gradient elution (Waters model 510). The mobile phase comprised a mixture of methanol and water containing PICA (tetrabutylammonium phosphate) (flow rate, 2 ml/min).…”

Synthesis of benzimidazole derivatives as potent β-glucuronidase inhibitors

“…In human body, b-glucuronidase is present in many body fluids and organs [3]. Increased activity of b-glucuronidase has resulted in various health issues that includes renal disorders [4], urinary tract infections [5,6], epilepsy [7,8], renal transplant rejection [9,10], neoplasm of bladder [11] and breast cancers [12]. Further, the enzyme has been found to be released into fluid in the cavities of synovial joints [13] and is involved in the disorders like those of rheumatoid arthritis [14].…”