86. Urea Formation in Mammalian Liver

Leuthardt [1938a] and Bach [1939] have expressed the opinion that in addition to the ornithine cycle there are other mechanisms of urea synthesis in the mammalian liver. Leuthardt [1938a] found that liver of starved guinea-pigs forms urea more rapidly from glutamine than from NH4Cl. He concluded that NH3 cannot be an intermediate in the urea formation from glutamine and that there is a more or less direct conversion of glutamine into urea. He suggested the following scheme: Glutamine + 2HCO' = urea+ pyrollidone carboxylic acid. (1) This scheme, however, is not in accordance with the fact that in liver tissue glutamine yields not pyrollidone carboxylic acid but glutamic acid [Krebs, 1935b], and Leuthardt [1938b] later appears to have given up the above scheme in favour of the more general idea that glutamine might act as a direct nitrogen donator to the 'urea forming system'. Bach [1939] proposed two further mechanisms of urea formation, viz. 'urea synthesis from citrulline by oxidative hydrolysis':