Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients
Titus Lau, … , Vernon R. Young, Leticia Castillo
Titus Lau, … , Vernon R. Young, Leticia Castillo
Published May 1, 2000
Citation Information: J Clin Invest. 2000;105(9):1217-1225. https://doi.org/10.1172/JCI7199.
View: Text | PDF
Article

Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients

Abstract

The kidneys are thought to be a major site of net de novo arginine synthesis, but the quantitative status of arginine metabolism and its substrate precursor relationship to nitric oxide (NO) synthesis in end stage renal disease (ESRD) patients have not been characterized. We have investigated kinetic aspects of whole body arginine metabolism in six patients with ESRD. They received two pre- and two post-hemodialysis intravenous tracer infusion studies with L-[guanidino-15N2]arginine and L-[13C]leucine during the first study, and L-[5-13C]arginine and L-[5-13C-ureido,5,5,2H2]citrulline during the second study. Arginine homeostasis in ESRD patients was found to be associated with a lower rate of arginine oxidation, and despite the decrease in renal function, the rate of de novo arginine synthesis appeared to be preserved. Plasma citrulline concentrations and flux were also elevated in these subjects compared with healthy adults. The rate of whole body NO synthesis was increased in the ESRD patients, but apparently not different pre- and post-hemodialysis therapy. The anatomic site(s) responsible for the maintenance of net de novo arginine synthesis and for the elevated NO synthesis and its pathophysiological importance in ESRD remain to be established.

Authors

Titus Lau, William Owen, Yong Ming Yu, Natan Noviski, Jeremy Lyons, David Zurakowski, Rita Tsay, Alfred Ajami, Vernon R. Young, Leticia Castillo

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Illustration of the tracers used on days 1 and 3, and their metabolic fa...
Illustration of the tracers used on days 1 and 3, and their metabolic fates. (a) Day 1: [1-13C]leucine (I) is converted to [1-13C]α-ketoisocaproate (II), which liberates 13CO2 (III) during its oxidative decarboxylation. L[guanidino-15N2]arginine (IV) liberates 15NO (V) and L-[15N-ureido]citrulline (VI) through the activity of NO synthase. (b) Day 3: L-[13C]ureido[5,5,H2]citrulline (VII) is converted to L-[13C-guanidino, 5,5,2H2] argenine (VIII), which is used as a measure of de novo arginine synthesis. L-[5-13C]arginine (IX) is converted to L-[5-13C]ornithine (X), which is then converted to L-[5-13C]glutamic acid (XI). The latter, via transamination, is then converted to [5-13C]α-ketoglutarate (XII), which upon decarboxylation by α-ketoglutarate dehydrogenase yields [13C]succinyl CoA (not shown). This releases its 13C as 13CO2 (III) during subsequent revolutions of the citric acid cycle.