Differences in lysine and arginine requirements among various species such as omnivores (humans, pigs, rats, dogs), carnivores (cats), herbivores (rabbits, horses), ruminants (cattle), poultry, and fish, are covered in detail in this article. Although lysine is classified as an indispensable amino acid across species, the classification of arginine as either an indispensable or dispensable amino acid is more ambiguous because of differences among species in rates of de novo arginine synthesis. Because lysine is most often the limiting amino acid in the diet, its requirement has been extensively studied. By use of the ideal protein concept, the requirements of the other indispensable amino acids can be extrapolated from the lysine requirement. The successful use of this concept in pigs is compared with potential application of the ideal protein concept in humans. The current dietary arginine requirement varies widely among species, with ruminants, rabbits, and rats having relatively low requirements and carnivores, fish, and poultry having high requirements. Interspecies differences in metabolic arginine utilization and reasons for different rates of de novo arginine synthesis are reviewed in detail, as these are the primary determinants of the dietary arginine requirement. There is presently no dietary requirement for humans of any age, although this needs to be reassessed, particularly in neonates. A thorough understanding of the factors contributing to the lysine and arginine requirements in different species will be useful in our understanding of human amino acid requirements.

In mature horses, feeding resulted in increased mammalian target of rapamycin signaling and the mechanism appeared to be independent of an increase in Akt phosphorylation at Ser⁴⁷³. Results indicate that adult horses may be able to increase rates of muscle protein synthesis in response to feeding and that dietary amino acids appear to be the main mediators of this effect.

Although neonatal piglets can synthesize some arginine from proline, there is a limit to this synthesis, and piglets fed an arginine-deficient diet have diminished whole-body arginine status. To help elucidate where the limitation in arginine synthesis may occur, our objective was to determine the most effective arginine precursor in 1-wk-old enterally fed piglets. Piglets were administered either an arginine-deficient (basal) diet [1.15 mmol arginine/(kg.d)] or the basal diet supplemented with equimolar [9.18 mmol/(kg.d)] amounts of proline (+Pro), ornithine (+Orn), citrulline (+Cit) or arginine (+Arg) for 5 d (n = 5/diet). Daily blood samples were taken and indicators of whole-body arginine status including plasma amino acid, ammonia, and urea concentrations were measured. A primed, constant intragastric (i.g.) infusion of l-[U-(14)C]proline was given to measure the proline to arginine conversion, and intravenous (i.v.) and i.g. infusions of l-[guanido-(14)C]arginine were given to determine arginine flux and to quantify the splanchnic extraction of dietary arginine. Piglets fed the +Cit and +Arg diets had lower plasma ammonia and urea concentrations (P < 0.05) and higher plasma arginine concentrations (P < 0.0001) and arginine fluxes (P < 0.05) than piglets fed the other 3 diets. Piglets fed +Cit and +Arg had a lower proline to arginine conversion (P < 0.05). During first-pass splanchnic metabolism, 52% of the dietary arginine was extracted, and this extraction was not affected by whole-body arginine status (P > 0.05). These data indicate that citrulline, but not ornithine or proline, is an effective arginine precursor, and that either citrulline formation or availability appears to limit arginine synthesis in neonatal piglets.

Urschel KL, Rafii M, Pencharz PB, Ball RO. A multitracer stable isotope quantification of the effects of arginine intake on whole body arginine metabolism in neonatal piglets. Am J Physiol Endocrinol Metab 293: E811-E818, 2007. First published June 26, 2007; doi:10.1152/ajpendo.00290.2007We have previously shown that deficient arginine intake increased the rate of endogenous arginine synthesis from proline. In this paper, we report in vivo quantification of the effects of arginine intake on total endogenous arginine synthesis, on the rates of conversion between arginine, citrulline, ornithine, and proline, and on nitric oxide synthesis. Male piglets, with gastric catheters for diet and isotope infusion and femoral vein catheters for blood sampling, received a complete diet for 2 days and then either a generous (ϩArg; 1.80 g⅐kg Ϫ1 ⅐day Ϫ1; n ϭ 5) or deficient (ϪArg; 0.20 g⅐kg Ϫ1 ⅐day Ϫ1; n ϭ 5) arginine diet for 5 days. On day 7, piglets received a primed, constant infusion of [guanido- ) from both proline (ϩArg: 42, ϪArg: 74, pooled SE: 5) and citrulline (ϩArg: 67, ϪArg: 120; pooled SE: 15) were higher in piglets receiving the ϪArg diet (P Ͻ 0.05); and for both diets proline accounted for ϳ60% of total endogenous arginine synthesis. The conversion of proline to citrulline (ϩArg: 39, ϪArg: 67, pooled SE: 6) was similar to the proline-to-arginine conversion, confirming that citrulline formation limits arginine synthesis from proline in piglets. Nitric oxide synthesis (mol⅐kg Ϫ1 ⅐h Ϫ1), measured by the rate conversion of [guanido-15 N2]arginine to [ureido-15 N]citrulline, was greater in piglets receiving the ϩArg diet (105) than in those receiving the ϪArg diet (46, pooled SE: 10; P Ͻ 0.05). This multi-isotope method successfully allowed many aspects of arginine metabolism to be quantified simultaneously in vivo. arginine synthesis; nitric oxide; arginine precursors ALTHOUGH THE CARBON BACKBONE of citrulline may come from either proline or glutamine/glutamate via pyrroline-5-carboxylate (P5C) or from arginine that is converted to ornithine via the action of arginase (EC no. 3.5.3.1), all the carbon that appears in endogenously synthesized arginine must come from citrulline. Therefore, the conversion of citrulline to arginine is the best measure of total endogenous arginine synthesis, and this method has been successfully used to measure whole body arginine synthesis in adult humans (9). In previous studies, we used the proline-to-arginine conversion as a measure of whole body arginine synthesis in neonatal piglets (27)(28)(29)31); however, how much of the total endogenous arginine synthesis in piglets that arises from proline is currently unknown. By comparing the rate of conversion of proline to arginine to the rate of the citrulline-to-arginine conversion, the relative importance of proline as an arginine precursor can be assessed.In a previous study, we found that the addition of either arginine or citrulline to an arginine-deficient basal diet resulted in similar improvements in whole body arginine statu...

We have shown that first-pass intestinal metabolism is necessary for ϳ50% of whole body arginine synthesis from its major precursor proline in neonatal piglets. Furthermore, the intestine is not the site of increased arginine synthesis observed during dietary arginine deficiency. Primed constant intravenous (iv) and intraportal (ip) infusions of L-[U-14 C]proline, and iv infusion of either L-[guanido-14 C]arginine or L-[4,5-3 H]arginine were used to measure first-pass hepatic arginine synthesis in piglets enterally fed either deficient (0.20 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) or generous (1.80 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) quantities of arginine for 5 days. Conversion of arginine to other urea cycle intermediates and arginine recycling were also calculated for both dietary treatments. Arginine synthesis (g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) from proline was greater in piglets (P Ͻ 0.05) fed the deficient arginine diet in both the presence (generous: 0.07; deficient: 0.17; pooled SE ϭ 0.01) and absence (generous: 0.06; deficient: 0.20; pooled SE ϭ 0.01) of first-pass hepatic metabolism. There was no net arginine synthesis from proline during first-pass hepatic metabolism regardless of arginine intake. Arginine conversion to urea, citrulline, and ornithine was significantly greater (P Ͻ 0.05) in piglets fed the generous arginine diet. Calculated arginine fluxes were significantly lower (P ϭ 0.01) for [4,5-3 H]arginine than for [guanido-14 C]arginine, and the discrepancy between the values was greater in piglets fed the deficient arginine diet (35% vs. 20%). Collectively, these findings show that first-pass hepatic metabolism is not a site of net arginine synthesis and that piglets conserve dietary arginine in times of deficiency by decreasing hydrolysis and increasing recycling.proline; arginine biosynthesis; first-pass metabolism IN WEEK-OLD PIGLETS, IT IS PROLINE and not glutamine/glutamate that is the major precursor for the carbon backbone required for arginine synthesis (7,25,31). Addition of proline to an arginine-free diet prevented severe hyperammonemia when neonatal piglets were enterally, but not parenterally, fed (7). These findings suggested that proline can act as an arginine precursor only when first-pass splanchnic metabolism is intact (7). Indeed, Bertolo et al. (4) showed that first-pass intestinal, and not hepatic or peripheral, metabolism was responsible for the conversion of proline to ornithine. These observations were presumably due to the primary localization of ornithine aminotransferase (OAT, EC 2.6.1.13) to the small intestine (18). However, a subsequent study found that although whole body arginine synthesis was twofold greater in enterally fed piglets receiving a deficient arginine diet relative to piglets fed a generous arginine diet, first-pass intestinal metabolism was necessary for 42-63% of whole body arginine synthesis and was not affected by arginine intake (31). Therefore, there must be sites other than first-pass intestinal metabolism involved in arginine synthesis in the neonatal piglet, and it is the synthesis a...