Growth disorders and homocysteine metabolism.

Inherited disorders of homocysteine metabolism produce accelerated growth and arteriosclerosis with myointimal hyperplasia. The growth of cell cultures from cystathionine synthetase deficient individuals with homocystinuria is characterized by abnormal contact inhibition and production of an aggregated proteoglycan matrix which binds excess sulfate. Homocysteic acid, a precursor of sulfate ester, increases the growth rate of normal guinea pigs. Synthesis of homocysteic acid from homocysteine thiolactone is more rapid in the livers of young animals than adults, and hypophysectomy results in a pattern of homocysteine thiolactone metabolism resembling that in liver of adult animals. Homocysteine thiolactone metabolism differs in guinea pig, an herbivorous species, and in rat, an omnivorous species. Sulfate binding by cultured human cells is slightly increased when homocysteic acid is present in the culture medium. These observations suggest a relationship between homocysteic acid and somatomedin, a serum polypeptide which mediates the action of growth hormone. The growth disorders associated with homocystinuria, including arteriosclerosis and accelerated growth, are believed to result from increased conversion of methionine to homocysteine thiolactone and homocysteic acid.