Transport and metabolism of sarcosine in hypersarcosinemic and normal phenotypes.
An adolescent male proband with hypersarcosinemia was discovered incidentally in a French-Canadian family; no specific disease was associated with the trait. The hypersarcosinemia is not diminished by dietary folic acid even in pharmacologic doses (30 mg/day). The normal absence of sarcosine dehydrogenase in cultured human skin fibroblasts and in leukocytes was confirmed, thus eliminating these tissues as useful sources for further investigation of mutant sarcosinemic phenotypes and genotypes. The response in plasma of sarcosine and glycine, after sarcosine loading, distinguished the normal subject from the subjects who were presumably homozygous and heterozygous for the hypersarcosinemia allele. Sarcosine clearance from plasma was delayed greatly (t(1/2), 6.1 hr) in the presumed homozygote and slightly (t(1/2), 2.2 hr) in the presumed heterozygote, while plasma glycine remained constant in the former and rose in the latter. Normal subjects clear sarcosine from plasma rapidly (t(1/2), 1.6 hr) while their plasma glycine trend is downward. The phenotypic responses suggest that hypersarcosinemia is an autosomal recessive trait in this pedigree. Renal tubular transport of sarcosine was normal in the proband even though he presumably lacked the sarcosine oxidation which should normally occur in kidney. Sarcosine catabolism is thus not important for its own renal uptake. Sarcosine interacts with proline and glycine during its absorption in vivo. Studies in vitro in rat kidney showed that sarcosine transport is mediated, saturable, and energy dependent. Sarcosine has no apparent transport system of its own; it uses the low K(m) transport systems for L-proline and glycine to a minor extent and a high K(m) system shared by these substances for the major uptake at concentrations encountered in hypersarcosinemia. Intracellular sarcosine at high concentration will exchange with glycine on one of these systems, which may explain a paradoxical improvement in renal transport of glycine after sarcosine loading in the hypersarcosinemic proband.
D000042:Absorption; D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D002247:Carbon Isotopes; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism; D006207:Half-Life; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000502:physiology; D007700:Kinetics; D010088:Oxidoreductases / Q000378:metabolism; D010641:Phenotype; D011392:Proline / Q000378:metabolism; D051381:Rats; D012521:Sarcosine / Q000097:blood* / Q000378:metabolism*; D012867:Skin / Q000166:cytology
D002247:Carbon Isotopes; D005492:Folic Acid; D011392:Proline; D010088:Oxidoreductases; D005998:Glycine; D012521:Sarcosine