Branched-chain amino acid carbon and nitrogen arteriovenous concentration differences across the ovine fetal hindlimb.

Abstract

During fasting, branched-chain amino acids (BCAA) are thought to be major sources of nitrogen for myocyte synthesis of alanine (Ala) and glutamine (Gln), as well as possible sources of carbon skeleton for Gln synthesis. To study the relationships between Ala, Gln, and BCAA, we utilized the chronic fetal lamb preparation and measured arteriovenous concentration differences of Ala, Gln, BCAA, and branched-chain alpha-keto acids across the fetal hindlimb. Studies were performed when the ewe was fed and repeated after 1 and 5 days of complete maternal fasting. Ala and Gln are released from fetal hindquarters during fasting (arteriovenous -9.6 +/- 5 and -8.8 +/- 4.1 mumol/liter), while arteriovenous differences for BCAA simultaneously increase by 65% as compared to the fed state. During fasting, total nitrogen exiting fetal hindlimb as Ala and Gln equals nitrogen entering as BCAA. Branched-chain alpha-keto acids are released from fetal hindquarters during the fed state as well as after 1 day of fasting; at 5 days of fasting only keto-isovalerate had a net negative arteriovenous difference. In all cases, the release was much smaller than the entry of the corresponding amino acid, as determined by simultaneously measured arteriovenous concentration differences. These results indicate: Ala and Gln are released from fetal hindlimb, as in postnatal animals, during fasting, shuttling nitrogen and carbon to liver and/or other tissues. There is negligible movement of BCAA carbon as the branched-chain alpha-keto acids from hindlimb to other tissues in the fetus. BCAA carbon taken up is utilized within the hindquarters. It may be used for tissue synthesis, as an energy source, or possibly for Gln synthesis.