Lactate inhibits citrulline and arginine synthesis from proline in pig enterocytes

Edgar Dillon, Darrell A. Knabe, Guoyao Wu

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Hypocitrullinemia and hypoargininemia but hyperprolinemia are associated with elevated plasma concentration of lactate in infants. Because the small intestine may be a major organ for initiating proline catabolism via proline oxidase in the body and is the major source of circulating citrulline and arginine in neonates, we hypothesized that lactate is an inhibitor of intestinal synthesis of citrulline and arginine from proline. To test this hypothesis, jejunum was obtained from 14-day-old suckling pigs for preparation of enterocyte mitochondria and metabolic studies. Mitochondria were used for measuring proline oxidase activity in the presence of 0-10 mM L-lactate. For metabolic studies, enterocytes were incubated at 37°C for 30 min in Krebs bicarbonate buffer (pH 7.4) containing 5 mM D-glucose, 2 mM L- glutamine, 2 mM L-[U-14C]proline, and 0, 1, 5, or 10 mM L-lactate. Kinetics analysis revealed noncompetitive inhibition of intestinal proline oxidase by lactate (decreased maximal velocity and unaltered Michaelis constant). Lactate had no effect on either activities of other enzymes for arginine synthesis from proline or proline uptake by enterocytes but decreased the synthesis of ornithine, citrulline, and arginine from proline in a concentration-dependent manner. These results demonstrate that lactate decreased intestinal synthesis of citrulline and arginine from proline via an inhibition of proline oxidase and provide a biochemical basis for explaining hyperprolinemia, hypocitrullinemia, and hypoargininemia in infants with hyperlactacidemia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume276
Issue number5 39-5
StatePublished - May 1999
Externally publishedYes

Fingerprint

Citrulline
Enterocytes
Proline
Proline Oxidase
Arginine
Lactic Acid
Swine
Mitochondria
Ornithine
Jejunum
Bicarbonates
Glutamine
Small Intestine
Buffers
Newborn Infant
Glucose
Enzymes

Keywords

  • Amino acids
  • Intestine
  • Pigs
  • Proline oxidase

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Lactate inhibits citrulline and arginine synthesis from proline in pig enterocytes. / Dillon, Edgar; Knabe, Darrell A.; Wu, Guoyao.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 276, No. 5 39-5, 05.1999.

Research output: Contribution to journalArticle

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