Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet

Abstract

Background & aims: It is not known whether arginine homeostasis is negatively affected by a "long term" dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healthy subjects.

Methods: Ten healthy adults received a complete amino acid diet for 1 week (control diet) and following a break period, six subjects received a 4-week arginine, proline, glutamate and aspartate-free diet (APF diet). The other four subjects continued for 4 weeks with the complete diet. On days 4 and 7 of the first week and days 25 and 28 of the 4-week period, the subjects received 24-h infusions of arginine, citrulline, leucine and urea tracers.

Results: During the 4-week APF, plasma arginine fluxes for the fed state, were significantly reduced. There were no significant differences for citrulline, leucine or urea fluxes. Arginine de novo synthesis was not affected by the APF intake. However, arginine oxidation was significantly decreased.

Conclusions: In healthy adults, homeostasis of arginine under a long term arginine- and precursor-free intake is achieved by decreasing catabolic rates, while de novo arginine synthesis is maintained.

Conflict of interest statement

Conflict of interest statement None of the authors have any conflict of interest with the funding agencies.

Figures

Figure 1

Experimental design used to explore a 4-week adaptation period to an arginine- and precursor-free (APF) diet. The isotopically labeled compounds used during the 24 h tracer infusions are indicated in the bottom of the tracer infusion figure.

Figure 2

(A) Isotopic enrichment of plasma l-[guanidino-15N2,5,5,2H2]arginine, l-[1-13C]leucine and [13C]urea during the last 6 or 8 h of the fed and fasting periods in subjects receiving the control diet at 1 and 4 weeks. (B) Isotopic enrichment of plasma l-[guanidino-15N2,5,5,2H2]arginine, [13C]leucine and [13C]urea during the last 6 or 8 h of the fed and fasting periods in subjects receiving the control diet for 1 week and APF diet during the 4-week period.

Figure 3

(A) Isotopic enrichment of plasma l-[5-13C]arginine, l-[13C-ureido, 5,5,2H2]citrulline and its labeled arginine derivative during the fed and fasting periods in subjects receiving the control diet at 1 and 4 weeks. (B) Isotopic enrichment of plasma l-[5-13C]arginine, l-[13C-ureido,5,5,2H2]citrulline and its labeled arginine derivative in subjects receiving the adequate diet for 1 week and APF diet during the 4-week period.

Figure 4

(A) Rates of 13CO2 production (V13CO2) derived from l-[1-13C]arginine tracer on days 7 and 28 and from l-[1-13C]leucine tracer on days 4 and 25 for the control group at 1 and 4 weeks. (B) Rates of 13CO2 production (V13CO2) derived from l-[1-13C]arginine on days 7 and 28 and from l-[1-13C]leucine tracer on days 4 and 25 for the APF group at 1 week adequate intake and 4 weeks APF.

Figure 5

Schematic representation of the contribution of proline, glutamate and aspartate to arginine synthesis. Alpha-ketoglutarate and oxaloacetate donate carbon skeleton for synthesis of glutamate and aspartate, respectively. l-Glutamic γ semialdehyde forms l-Δ′-pyrroline-5-carboxylic acid to yield l-proline and ornithine. Ornithine and carbamyl phosphate will form citrulline, and aspartate will yield arginino succinate, an intermediate precursor of arginine.