A metabolic investigation of urinary β-aminoisobutyric acid excretion in man

Abstract

Comparative effects of various orally administered β-aminoisobutyric acid (BAIB) precursors on urinary BAIB excretion in genetically determined high and low excretors were studied in man. Orally administered thymine gives rise to more urinary BAIB than equal amounts of dihydrothymine (DHT) or β-ureidoisobutyric acid (BUIB) which metabolically are closer to BAIB (thymine DHT ⇒ 4 BUIB → BAIB). However, this phenomenon is shown to be due to the poorer in vivo uptake of DHT and BUIB than thymine. At low levels of BAIB precursors (thymine, DHT, and BUIB), a marked difference in the urinary BAIB excretion rate occurs between low and high excretors; whereas, at high levels, this difference is almost eliminated. The data rule out the possibility of this difference resulting from a metabolic block in the thymine → BAIB pathway in low excretors. Several other possible explanations are pointed out. Comparative aspects of the thymine → BAIB pathway in man, rat, and the mouse are discussed. Although this pathway is functional in all three species, marked differences exist which serve to explain why urinary BAIB is found normally only in man. Experiments with other test substances (thymidine, cytosine, orotic acid, thiamine, and valine) indicate that thymine is probably the only significant source of urinary BAIB in man.