Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 May;51(5):1195–1202. doi: 10.1172/JCI106913

Amino acid metabolism during starvation in human pregnancy

Philip Felig 1,2, Young Jin Kim 1,2, Vincent Lynch 1,2, Rosa Hendler 1,2
PMCID: PMC292250  PMID: 5020432

Abstract

To evaluate the factors regulating gluconeogenesis in pregnancy, plasma amino acid levels were determined during the course of an 84-90 hr fast in physically healthy women studied during wk 16-22 of gestation (before undergoing therapeutic abortion), and in nonpregnant controls. The effect of pregnancy on the glycemic response to exogenous alanine administration during starvation was also investigated.

In the nonpregnant group fasting resulted in a 2- to 3-fold increase in the levels of plasma valine, leucine, isoleucine, and α-aminobutyrate, while the concentration of alanine and glycine fell. In the pregnant group, the levels of most amino acids were significantly reduced in the postabsorptive state. With starvation, the plasma concentration of alanine fell more rapidly in the pregnant group and was significantly below that of the nonpregnant subjects for the first 60 hr of the fast. In contrast, a significant elevation in plasma glycine, serine, and threonine was observed in the pregnant group after 84 hr of fasting, whereas similar increments were not demonstrable until after 10 days of fasting in previously studied nonpregnant obese subjects. Paralleling the changes in maternal plasma, amniotic fluid levels of valine, leucine, and isoleucine increased while that of alanine fell during the fast.

Although the plasma glucose concentration was lower in the pregnant group at termination of the fast, intravenous alanine administration (0.15 g/kg), resulted in a prompt, comparable increase (20-25 mg/100 ml) in plasma glucose in both groups of subjects.

It is concluded that (a) pregnancy accelerates and exaggerates the hypoalaninemic and hyperglycinemic effects of starvation; (b) lack of key endogenous substrate rather than altered intrahepatic processes may limit hepatic gluconeogenesis in pregnancy and contribute to gestational hypoglycemia; (c) maternal caloric deprivation profoundly alters the levels of amino acids in amniotic fluid.

Full text

PDF
1195

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adibi S. A. Influence of dietary deprivations on plasma concentration of free amino acids of man. J Appl Physiol. 1968 Jul;25(1):52–57. doi: 10.1152/jappl.1968.25.1.52. [DOI] [PubMed] [Google Scholar]
  2. Block W. D., Markovs M. E., Steele B. F. Comparison between free amino acid levels in plasma deproteinated with picric acid and with sulfosalicylic acid. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1089–1091. doi: 10.3181/00379727-122-31333. [DOI] [PubMed] [Google Scholar]
  3. CHRISTENSEN P. J., DATE J. W., SCHONHEYDER F., VOLQVARTZ K. Amino acids in blood plasma and urine during pregnancy. Scand J Clin Lab Invest. 1957;9(1):54–61. doi: 10.3109/00365515709088114. [DOI] [PubMed] [Google Scholar]
  4. Carlsten A., Hallgren B., Jagenburg R., Svanborg A., Werkö L. Arterio-hepatic venous differences of free fatty acids and amino acids. Studies in patients with diabetes or essential hypercholesterolemia, and in healthy individuals. Acta Med Scand. 1967 Feb;181(2):199–207. doi: 10.1111/j.0954-6820.1967.tb07246.x. [DOI] [PubMed] [Google Scholar]
  5. Emery A. E., Burt D., Nelson M. M., Scrimgeour J. B. Antenatal diagnosis and aminoacid composition of amniotic fluid. Lancet. 1970 Jun 20;760(1):1307–1308. doi: 10.1016/s0140-6736(70)91908-2. [DOI] [PubMed] [Google Scholar]
  6. Felig P., Lynch V. [Starvation in human pregnancy: hypoglycemia, hypoinsulinemia, and hyperketonemia]. Science. 1970 Nov 27;170(3961):990–992. doi: 10.1126/science.170.3961.990. [DOI] [PubMed] [Google Scholar]
  7. Felig P., Marliss E., Cahill G. F., Jr Plasma amino acid levels and insulin secretion in obesity. N Engl J Med. 1969 Oct 9;281(15):811–816. doi: 10.1056/NEJM196910092811503. [DOI] [PubMed] [Google Scholar]
  8. Felig P., Marliss E., Owen O. E., Cahill G. F., Jr Blood glucose and cluconeogenesis in fasting man. Arch Intern Med. 1969 Mar;123(3):293–298. [PubMed] [Google Scholar]
  9. Felig P., Marliss E., Pozefsky T., Cahill G. F., Jr Amino acid metabolism in the regulation of gluconeogenesis in man. Am J Clin Nutr. 1970 Jul;23(7):986–992. doi: 10.1093/ajcn/23.7.986. [DOI] [PubMed] [Google Scholar]
  10. Felig P., Owen O. E., Wahren J., Cahill G. F., Jr Amino acid metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):584–594. doi: 10.1172/JCI106017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Felig P., Pozefsky T., Marliss E., Cahill G. F., Jr Alanine: key role in gluconeogenesis. Science. 1970 Feb 13;167(3920):1003–1004. doi: 10.1126/science.167.3920.1003. [DOI] [PubMed] [Google Scholar]
  12. Felig P., Wahren J. Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest. 1971 Aug;50(8):1702–1711. doi: 10.1172/JCI106659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. GHADIMI H., PECORA P. FREE AMINO ACIDS OF CORD PLASMA AS COMPARED WITH MATERNAL PLASMA DURING PREGNANCY. Pediatrics. 1964 Apr;33:500–506. [PubMed] [Google Scholar]
  14. HUGGETT A. S., NIXON D. A. Use of glucose oxidase, peroxidase, and O-dianisidine in determination of blood and urinary glucose. Lancet. 1957 Aug 24;273(6991):368–370. doi: 10.1016/s0140-6736(57)92595-3. [DOI] [PubMed] [Google Scholar]
  15. Herrera E., Knopp R. H., Freinkel N. Carbohydrate metabolism in pregnancy. VI. Plasma fuels, insulin, liver composition, gluconeogenesis, and nitrogen metabolism during late gestation in the fed and fasted rat. J Clin Invest. 1969 Dec;48(12):2260–2272. doi: 10.1172/JCI106192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kerr G. R. The free amino acids of serum during development of Macaca mulatta. II. During pregnancy and fetal life. Pediatr Res. 1968 Nov;2(6):493–500. doi: 10.1203/00006450-196811000-00007. [DOI] [PubMed] [Google Scholar]
  17. Kim Y. J., Felig P. Plasma chorionic somatomammotropin levels during starvation in midpregnancy. J Clin Endocrinol Metab. 1971 Jun;32(6):864–867. doi: 10.1210/jcem-32-6-864. [DOI] [PubMed] [Google Scholar]
  18. Levy H. L., Montag P. P. Free amino acids in human amniotic fluid. A quantitative study by ion-exchange chromatography. Pediatr Res. 1969 Mar;3(2):113–120. doi: 10.1203/00006450-196903000-00002. [DOI] [PubMed] [Google Scholar]
  19. Lindblad B. S., Rahimtoola R. J., Said M., Haque Q., Khan N. The venous plasma free amino acid levels of mother and child during delivery. 3. In a lower socio-economic group of a refugee area in Karachi, West Pakistan, with special reference to the "small for dates" syndrome. Acta Paediatr Scand. 1969 Sep;58(5):497–505. doi: 10.1111/j.1651-2227.1969.tb04751.x. [DOI] [PubMed] [Google Scholar]
  20. Marliss E. B., Aoki T. T., Pozefsky T., Most A. S., Cahill G. F., Jr Muscle and splanchnic glutmine and glutamate metabolism in postabsorptive andstarved man. J Clin Invest. 1971 Apr;50(4):814–817. doi: 10.1172/JCI106552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Metzger B. E., Agnoli F. S., Freinkel N. Effect of sex and pregnancy on formation of urea and ammonia during gluconeogenesis in the perfused rat liver. Horm Metab Res. 1970 Nov;2(6):367–368. doi: 10.1055/s-0028-1096820. [DOI] [PubMed] [Google Scholar]
  22. Milunsky A., Littlefield J. W., Kanfer J. N., Kolodny E. H., Shih V. E., Atkins L. Prenatal genetic diagnosis (second of three parts). N Engl J Med. 1970 Dec 24;283(26):1441–1447. doi: 10.1056/NEJM197012242832605. [DOI] [PubMed] [Google Scholar]
  23. Müller W. A., Faloona G. R., Unger R. H. The effect of alanine on glucagon secretion. J Clin Invest. 1971 Oct;50(10):2215–2218. doi: 10.1172/JCI106716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nadler H. L., Gerbie A. B. Role of amniocentesis in the intrauterine detection of genetic disorders. N Engl J Med. 1970 Mar 12;282(11):596–599. doi: 10.1056/NEJM197003122821105. [DOI] [PubMed] [Google Scholar]
  25. OWEN E. E., ROBINSON R. R. Amino acid extraction and ammonia metabolism by the human kidney during the prolonged administration of ammonium chloride. J Clin Invest. 1963 Feb;42:263–276. doi: 10.1172/JCI104713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Owen O. E., Felig P., Morgan A. P., Wahren J., Cahill G. F., Jr Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574–583. doi: 10.1172/JCI106016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pozefsky T., Felig P., Tobin J. D., Soeldner J. S., Cahill G. F., Jr Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels. J Clin Invest. 1969 Dec;48(12):2273–2282. doi: 10.1172/JCI106193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. SCOW R. O., CHERNICK S. S., BRINLEY M. S. HYPERLIPEMIA AND KETOSIS IN THE PREGNANT RAT. Am J Physiol. 1964 Apr;206:796–804. doi: 10.1152/ajplegacy.1964.206.4.796. [DOI] [PubMed] [Google Scholar]
  29. STEIN W. H., MOORE S. The free amino acids of human blood plasma. J Biol Chem. 1954 Dec;211(2):915–926. [PubMed] [Google Scholar]
  30. Saunders S. J., Truswell A. S., Barbezat G. O., Wittman W., Hansen J. D. Plasma free aminoacid pattern in protein-calorie malnutrition. Reappraisal of its diagnostic value. Lancet. 1967 Oct 14;2(7520):795–797. doi: 10.1016/s0140-6736(67)92233-7. [DOI] [PubMed] [Google Scholar]
  31. Williamson J. R. Effects of fatty acids, glucagon and anti-insulin serum on the control of gluconeogenesis and ketogenesis in rat liver. Adv Enzyme Regul. 1967;5:229–255. doi: 10.1016/0065-2571(67)90019-2. [DOI] [PubMed] [Google Scholar]
  32. Young M., Prenton M. A. Maternal and fetal plasma amino acid concentrations during gestation and in retarded fetal growth. J Obstet Gynaecol Br Commonw. 1969 Apr;76(4):333–334. doi: 10.1111/j.1471-0528.1969.tb05842.x. [DOI] [PubMed] [Google Scholar]
  33. Zinneman H. H., Seal U. S., Doe R. P. Urinary amino acids in pregnancy, following progesterone, and estrogen-progesterone. J Clin Endocrinol Metab. 1967 Mar;27(3):397–405. doi: 10.1210/jcem-27-3-397. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES