OVINE FETAL LEUCINE KINETICS AND PROTEIN-METABOLISM DURING ACUTE METABOLIC-ACIDOSIS

Fetal acidosis is associated with poor fetal growth. Because protein a ccretion is an important component of fetal growth, we used seven chro nically prepared fetal lambs (10-16 days postoperation) to find whethe r fetal metabolic acidosis affected fetal protein accretion, and, if s o, whether such effects were due to decreased synthesis or increased b reakdown of proteins. Fetal leucine kinetics were measured during infu sion of [1-C-14] leucine by the reciprocal pool method. After control measurements, metabolic acidosis was induced by fetal infusion of 0.5 N HCl, and the measurements were repeated. Although fetal leucine conc entration rose (164 +/- 11 vs. 216 +/- 15 mu M; P < 0.001), fetal leuc ine uptake fell during acidosis (3.33 +/- 0.30 vs. 1.43 +/- 0.35 mu mo l . kg(-)1 . min(-1); P < 0.05). However, the influx of leucine from p rotein breakdown increased (12.6 +/- 2.6 vs. 14.7 +/- 2.6 mu mol . kg( -1) . min(-1); P < 0.02). The incorporation of leucine into fetal prot ein was unaffected by acidosis, so that fetal protein accretion fell ( 0.48 +/- 1.04 vs. -2.32 +/- 1.53 mu mol . kg(-1) . min(-1); P < 0.001) . Fetal leucine decarboxylation increased during acidosis (2.85 +/- 0. 33 vs. 3.75 +/- 0.61 mu mol . kg(-1) . min(-1); P < 0.05). We conclude that fetal metabolic acidosis stimulates pathways to degrade both pro tein and at least one of the subsequently derived amino acids, leucine . The consequence of such changes induced by acidosis is decreased pro tein accretion, a finding incompatible with normal fetal growth.