Ovine fetal leucine kinetics and protein metabolism during acute metabolic acidosis.
Fetal acidosis is associated with poor fetal growth. Because protein accretion is an important component of fetal growth, we used seven chronically prepared fetal lambs (10-16 days postoperation) to find whether fetal metabolic acidosis affected fetal protein accretion, and, if so, whether such effects were due to decreased synthesis or increased breakdown of proteins. Fetal leucine kinetics were measured during infusion of [1-(14)C]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 concentration rose (164 +/- 11 vs. 216 +/- 15 microM; P < 0.001), fetal leucine uptake fell during acidosis (3.33 +/- 0.30 vs. 1.43 +/- 0.35 micromol x kg(-1) x min(-1); P < 0.05). However, the influx of leucine from protein breakdown increased (12.6 +/- 2.6 vs. 14.7 +/- 2.6 micromol x kg(-1) x min(-1); P < 0.02). The incorporation of leucine into fetal protein was unaffected by acidosis, so that fetal protein accretion fell (0.48 +/- 1.04 vs. -2.32 +/- 1.53 micromol x kg(-1) x min(-1); P < 0.001). Fetal leucine decarboxylation increased during acidosis (2.85 +/- 0.33 vs. 3.75 +/- 0.61 micromol x kg(-1) x min(-1); P < 0.05). We conclude that fetal metabolic acidosis stimulates pathways to degrade both protein and at least one of the subsequently derived amino acids, leucine. The consequence of such changes induced by acidosis is decreased protein accretion, a finding incompatible with normal fetal growth.
Milley
J R
JR
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132, USA.
D000138:Acidosis / Q000378:metabolism*; D000208:Acute Disease; D000818:Animals; D050260:Carbohydrate Metabolism; D005312:Fetal Blood; D005333:Fetus / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000378:metabolism*; D010101:Oxygen Consumption; D011506:Proteins / Q000378:metabolism*; D012756:Sheep / Q000196:embryology
D006728:Hormones; D011506:Proteins; D007930:Leucine