Amino acid metabolism during prolonged starvation.

Plasma concentration, splanchnic and renal exchange, and urinary excretion of 20 amino acids were studied in obese subjects during prolonged (5-6 wk) starvation. Splanchnic amino acid uptake was also investigated in postabsorptive and briefly (36-48 hr) fasted subjects.A transient increase in plasma valine, leucine, isoleucine, methionine, and alpha-aminobutyrate was noted during the 1st wk of starvation. A delayed, progressive increase in glycine, threonine, and serine occurred after the 1st 5 days. 13 of the amino acids ultimately decreased in starvation, but the magnitude of this diminution was greatest for alanine which decreased most rapidly during the 1st week of fasting. In all subjects alanine was extracted by the splanchnic circulation to a greater extent than all other amino acids combined. Brief fasting resulted in an increased arterio-hepatic venous difference for alanine due to increased fractional extraction. After 5-6 wk of starvation, a marked falloff in splanchnic alanine uptake was attributable to the decreased arterial concentration. Prolonged fasting resulted in increased glycine utilization by the kidney and in net renal uptake of alanine. It is concluded that the marked decrease in plasma alanine is due to augmented and preferential splanchnic utilization of this amino acid in early starvation resulting in substrate depletion. Maintenance of the hypoalaninemia ultimately serves to diminish splanchnic uptake of this key glycogenic amino acid and is thus an important component of the regulatory mechanism whereby hepatic gluconeogenesis is diminished and protein catabolism is minimized in prolonged fasting. The altered renal extraction of glycine and alanine is not due to increased urinary excretion but may be secondary to the increased rate of renal gluconeogenesis observed in prolonged starvation.

[1]  W. Block,et al.  Comparison Between Free Amino Acid Levels in Plasma Deproteinated with Picric Acid and with Sulfosalicylic Acid.∗ , 1966, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[2]  M. Swendseid,et al.  PROLONGED STARVATION AS TREATMENT FOR SEVERE OBESITY. , 1964, JAMA.

[3]  W. Stein.  A chromatographic investigation of the amino acid constituents of normal urine. , 1953, The Journal of biological chemistry.

[4]  H. Krebs,et al.  The rate of gluconeogenesis from various precursors in the perfused rat liver. , 1967, The Biochemical journal.

[5]  J. Rathbun,et al.  CITRULLINURIA. , 1963, Pediatrics.

[6]  P. Felig,et al.  Liver and kidney metabolism during prolonged starvation. , 1969, The Journal of clinical investigation.

[7]  D. Kipnis,et al.  Hormone-fuel interrelationships during fasting. , 1966, The Journal of clinical investigation.

[8]  G F Cahill,et al.  Brain metabolism during fasting. , 1967, The Journal of clinical investigation.

[9]  F. Nuttall,et al.  Effect of Endogenous Insulin on Human Amino Acid Metabolism , 1966, Diabetes.

[10]  S. Moore,et al.  Automatic recording apparatus for use in the chromatography of amino acids. , 1958, Federation proceedings.

[11]  Elvehjem Ca,et al.  Availability of amino acids in vivo. , 1954 .

[12]  S. Adibi.  Influence of dietary deprivations on plasma concentration of free amino acids of man. , 1968, Journal of applied physiology.

[13]  W. Beisel,et al.  Circadian Periodicity of Blood Amino-acids in Adult Men , 1967, Nature.

[14]  A. Svanborg,et al.  Amino acids and free fatty acids in plasma in diabetes. I. The effect of insulin on the arterial levels. , 2009, Acta medica Scandinavica.

[15]  D. Williamson,et al.  Concentrations of free glucogenic amino acids in livers of rats subjected to various metabolic stresses. , 1967, The Biochemical journal.

[16]  I. Wool,et al.  Concentration of Amino-acids in Rat Muscle and Plasma , 1964, Nature.

[17]  P. Hamilton,et al.  ION EXCHANGE CHROMATOGRAPHY OF THE FREE AMINO ACIDS IN THE PLASMA OF THE NEWBORN INFANT. , 1965, Pediatrics.

[18]  H. Krebs.  The Metabolic Fate of Amino Acids , 1964 .

[19]  P. Felig,et al.  Insulin blockade of amino acid release by human forearm tissues. , 1968, Transactions of the Association of American Physicians.

[20]  W. Hoffman.  A RAPID PHOTOELECTRIC METHOD FOR THE DETERMINATION OF GLUCOSE IN BLOOD AND URINE , 1937 .

[21]  A. Morgan,et al.  The absorption by immature and adult rats of amino acids from raw and autoclaved fresh pork. , 1958, The Journal of nutrition.

[22]  A. Freedman,et al.  Pyruvate Metabolism and Control: Factors Affecting Pyruvic Carboxylase Activity , 1964, Science.

[23]  C. G. Webb,et al.  Evidence for the Release of Individual Amino-acids from the Resting Human Forearm , 1965, Nature.

[24]  C. Elvehjem,et al.  Availability of amino acids in vivo. , 1954, The Journal of biological chemistry.

[25]  W. Gerok,et al.  Control of the levels of free amino acids in plasma by the liver. , 1965, Biochemische Zeitschrift.

[26]  S. Freeman,et al.  Free plasma levels and urinary excretion of eighteen amino acids in normal and diabetic dogs. , 1951, The American journal of physiology.

[27]  C. Elvehjem,et al.  New method for cannulating the portal vein of dogs. , 1953, Journal of Biological Chemistry.

[28]  S. Moore,et al.  The free amino acids of human blood plasma. , 1954, The Journal of biological chemistry.

[29]  A. Daniels,et al.  Further studies of the effect of insulin on the amino acid content of blood. , 1928 .

[30]  Homer W. Smith.  Principles of Renal Physiology , 1957 .

[31]  H. Taussky,et al.  ON THE COLORIMETRIC DETERMINATION OF CREATININE BY THE JAFFE REACTION , 1945 .

[32]  A. Svanborg,et al.  Arterio-hepatic venous differences of free fatty acids and amino acids. Studies in patients with diabetes or essential hypercholesterolemia, and in healthy individuals. , 2009, Acta medica Scandinavica.

[33]  H. Lardy,et al.  METABOLIC AND HORMONAL CONTROL OF PHOSPHOENOLPYRUVATE CARBOXYKINASE AND MALIC ENZYME IN RAT LIVER. , 1963, The Journal of biological chemistry.