To determine whether circulating citrulline can be manipulated in vivo in humans, and, if so, whether citrulline availability affects the levels of related amino acids, nitric oxide, urinary citrulline, and urea nitrogen, 10 healthy volunteers were studied on 3 separate days: 1) under baseline conditions; 2) after a 24-h treatment with phenylbutyrate (0.36 g.kg(-1).day(-1)), a glutamine "trappi...

The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal, it only accounts for ~60-70% of the citrulline produced. Because the only known fate for citrull...

L-Citrulline is a non-essential but still important amino acid that released from enterocytes. Because plasma levels are reduced in case of impaired intestinal function, it has become biomarker to monitor integrity. Moreover, oxidative stress induces protein citrullination, and antibodies against anti-citrullinated proteins useful rheumatoid diseases. Citrullinated histones, however, may even p...

The ornithine + citrulline -+ arginine cycle of urea synthesis originally proposed by Krebs and Henseleit (1) has had increasing experimental support (2-10). The position of citrulline in the cycle, however, has been questioned (11). With the advent of the successful separation of the two over-all enzymatic steps, ornithine -+ citrulline and citrulline -+ arginine (lo), from the intact cellular...

The kidney is a major site of arginine synthesis where citrulline is converted to arginine via argininosuccinate synthase (ASS) and lyase (ASL). The rate-limiting step in arginine synthesis by the normal kidney is the rate of citrulline delivery and uptake to the renal cortex. We tested whether with chronic kidney disease (CKD) renal arginine synthesis may be compromised. Using the 5/6 renal ab...

BACKGROUND Plasma citrulline is a biomarker of enterocyte mass and function in humans. OBJECTIVE We evaluated citrulline in the reemerging context of diarrhea in HIV-infected patients receiving highly active antiretroviral therapy. DESIGN This study prospectively measured citrulline in 6 groups of HIV-1 patients (n = 115): 1) undetectable viral load without chronic diarrhea (a; n = 40) and ...

Low plasma citrulline levels have been associated with a reduction of functional gut mass in various clinical situations. In critically ill patients, citrulline variations are tricky to interpret because of sepsis, vascular abnormalities, and multiple organ failure. In the previous issue of Critical Care, Ware and colleagues made an important contribution by demonstrating that very low citrulli...

The amino acid citrulline is poorly represented in food, except for the Cucurbitaceae family of fruits (watermelons, etc.) and sap from birch trees, which have both been used in the treatment of reproductive disorders for centuries. Recently, an interesting observation was published regarding citrulline as a promising candidate biomarker of abnormal embryogenesis. Our study was undertaken to in...

AIMS Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can be converted to l-citrulline and nitric oxide (NO) by the enzyme NO synthase....