FORMATION OF UREA IN LIVER HOMOGENATES FROM CITRULLINE AND VARIOUS N-ALKYL DERIVATIVES OF ASPARTIG ACID

Abstract

The effects of various N-alkylated derivatives of aspartic acid on the synthesis of urea by rat liver homogenates have been studied. At 5 × 10⁻³ M concentration, N-methyl, N-ethyl, N-isopropyl, and N-cyclohexyl aspartic acids are not utilized and have no effect on the formation of urea. At this concentration, N-allyl-DL-aspartic acid inhibits the formation of endogenous urea by 77%. At concentrations of 2.5 to 7.5 × 10⁻² M, N-methyl, N-ethyl, and N-isopropyl aspartic acids slightly increase the formation of endogenous urea; this is about 15% of the value obtained when aspartic acid alone is added at the same concentration. In the case of simple N-alkylated aspartic acids, liver homogenates are able to cleave the alkylated chain with the result that a small amount of urea synthesis is possible. N-allylaspartic acid totally inhibits the formation of urea from aspartic acid at a relatively low concentration of 6.2 × 10⁻³ M. N-cyclohexylaspartic acid has also an inhibitory effect which is ten times less pronounced than that of the N-allyl derivative.Natural amino acids such as DL- and L-valine, DL- and L-leucine, DL- and L-lysine, DL-alanine and glycine, at concentrations of 1.2 to 5 × 10⁻² M, also inhibit the formation of urea. This inhibition is probably due to the fact that other metabolic pathways, used by these amino acids, have priority over the formation of urea. Amino acid analogues, such as 1-aminocyclopentane carboxylic acid and 1-amino-2-methylcyclopentane-carboxylic acid, do not have any effect on the synthesis of urea.A free amino group in the aspartic acid molecule seems to be essential for the synthesis of argininosuccinic acid.