Glutamine synthesis in the developing porcine placenta.
Glutamine plays a vital role in fetal carbon and nitrogen metabolism and exhibits the highest fetal:maternal plasma ratio among all amino acids in pigs. Such disparate glutamine levels between mother and fetus suggest that glutamine may be actively synthesized and released into the fetal circulation by the porcine placenta. We hypothesized that branched-chain amino acid (BCAA) metabolism in the placenta plays an important role in placental glutamine synthesis. This hypothesis was tested by studying conceptuses from gilts on Days 20, 30, 35, 40, 45, 50, 60, 90, or 110 of gestation (n = 6 per day). Placental tissue was analyzed for amino acid concentrations, BCAA transport, BCAA degradation, and glutamine synthesis as well as the activities of related enzymes (including BCAA transaminase, branched-chain alpha-ketoacid dehydrogenase, glutamine synthetase, glutamate-pyruvate transaminase, and glutaminase). On all days of gestation, rates of BCAA transamination were much greater than rates of branched-chain alpha-ketoacid decarboxylation. The glutamate generated from BCAA transamination was primarily directed to glutamine synthesis and, to a much lesser extent, alanine production. Placental BCAA transport, BCAA transamination, glutamine synthesis, and activities of related enzymes increased markedly between Days 20 and 40 of gestation, as did glutamine in fetal allantoic fluid. Accordingly, placental BCAA levels decreased after Day 20 of gestation in association with a marked increase in BCAA catabolism and concentrations of glutamine. There was no detectable catabolism of glutamine in pig placenta throughout pregnancy, which would ensure maximum output of glutamine by this tissue. These novel results demonstrate glutamine synthesis from BCAAs in pig placentae, aid in explaining the abundance of glutamine in the fetus, and provide valuable insight into the dynamic role of the placenta in fetal metabolism and nutrition.
Self
Jon T
JT
Department of Animal Science, Texas A&M University, College Station, Texas 77843-2471, USA.
Spencer
Thomas E
TE
Johnson
Greg A
GA
Hu
Jianbo
J
Bazer
Fuller W
FW
Wu
Guoyao
G
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000378:metabolism; D000409:Alanine / Q000096:biosynthesis; D000410:Alanine Transaminase / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000096:biosynthesis*; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D013552:Swine / Q000378:metabolism; D000637:Transaminases / Q000378:metabolism
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D005973:Glutamine; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000637:Transaminases; D000410:Alanine Transaminase; C019798:branched-chain-amino-acid transaminase; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase; D000409:Alanine