Effect of post-ruminal guanidinoacetic acid supplementation on creatine synthesis and plasma homocysteine concentrations in cattle

Abstract

Creatine stores high-energy phosphate bonds in muscle, which is critical for muscle activity. In animals, creatine is synthesized in the liver from guanidinoacetic acid (GAA) with methylation by S-adenosylmethionine. Because methyl groups are used for the conversion of GAA to creatine, methyl group deficiency may occur as a result of GAA supplementation. With this study, the metabolic responses of cattle to post-ruminal supplementation of GAA were evaluated with and without methionine (Met) supplementation as a source of methyl groups. Six ruminally cannulated Holstein heifers (520 kg) were used in a split-plot design with treatments arranged as a 2 × 5 factorial. The main plot treatments were 0 or 12 g/d of l-Met arranged in a completely randomized design; three heifers received each main plot treatment throughout the entire experiment. Subplot treatments were 0, 10, 20, 30, and 40 g/d of GAA, with GAA treatments provided in sequence from lowest to highest over five 6-d periods. Treatments were infused continuously to the abomasum. Heifers were limit-fed twice daily a diet consisting of (dry matter basis) 5.3 kg/d rolled corn, 3.6 kg/d alfalfa hay, and 50 g/d trace-mineralized salt. Plasma Met increased (P < 0.01) when Met was supplemented, but it was not affected by supplemental GAA. Supplementing GAA linearly increased plasma arginine (% of total amino acids) and plasma concentrations of GAA and creatinine (P < 0.001). Plasma creatine was increased at all levels of GAA except when 40 g/d of GAA was supplemented with no Met (GAA-quadratic × Met, P = 0.07). Plasma homocysteine was not affected by GAA supplementation when heifers received 12 g/d Met, but it was increased when 30 or 40 g/d of GAA was supplemented without Met (GAA-linear × Met, P = 0.003); increases were modest and did not suggest a dangerous hyperhomocysteinemia. Urinary concentrations of GAA and creatine were increased by all levels of GAA when 12 g/d Met was supplemented; increasing GAA supplementation up to 30 g/d without Met increased urinary GAA and creatine concentrations, but 40 g/d GAA did not affect urine concentrations of GAA and creatine when no Met was supplemented. Overall, post-ruminal GAA supplementation increased creatine supply to cattle. A methyl group deficiency, demonstrated by modest increases in plasma homocysteine, became apparent when 30 or 40 g/d of GAA was supplemented, but it was ameliorated by 12 g/d Met.

Effects of Dietary Guanidinoacetic Acid on the Feed Efficiency, Blood Measures, and Meat Quality of Jinjiang Bulls

“…Could there be a GAMT catalytic reaction that occurs in the body after dietary GAA supplementation? This may be evidenced from the serum metabolites HCY and CRE, given that HCY is the end-product of the methylation reaction on GAA (20,24) and CRE is the endproduct of CK catalyzing PCr in an energy releasing reaction (20,(40)(41)(42)(43)(44). In our study, we found that dietary GAA increased the HCY content of plasma, and CRE in both serum and LT muscles, indicating a substantial GAMT catalytic reaction and energy buffering effect.…”

“…At present, the existing literature (20,24,31,32) and our study revealed that GAA influenced beef growth and feed efficiency in bulls. In addition, GAA influenced body growth and feed efficiency in other ruminants (37)(38)(39), and also in poultry and other livestocks (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

“…Combining the results of the aforementioned previous studies (24,31,32) with our results for blood measures, ADG and the F:D ratio, it could be inferred that 0.05-0.4% GAA is a suitable supplementation dosage for a bull's diet given subtle differences between different beef breeds, feeding models, and dietary components. This finding is probably related to the potential for ruminal degradation and utilization of GAA in rumen microbiota from different ruminant hosts (20)(21)(22)(23)(24). Bulls have high muscle growth efficiency and are favored by Chinese farmers than cows (18).…”

“…, Speer et al (23), and Li et al (24) argued that the potential for ruminal degradation would need to be considered if GAA was provided to beef cattle through their diet. Potentially, supplementing a diet with an optimal dosage of GAA could produce effects similar to that of non-ruminant animals (20)(21)(22)(23)(24).…”

Machine learning applied to serum and cerebrospinal fluid metabolomes revealed altered arginine metabolism in neonatal sepsis with meningoencephalitis

“…Creatine is synthesized in the liver by GAA through S-adenosylmethionine methylation, and is essential for muscle activity. Phosphokinase catalyzes creatine to form high-energy creatine phosphate, and creatine phosphate is hydrolyzed to release energy and creatinine and phosphoric acid when energy is needed by the body [43] . We found that the serum phosphoric acid concentration was significantly lower in the group with meningoencephalitis compared with its concentration in the group without meningoencephalitis, which suggests the presence of energy homeostasis in neonatal sepsis with meningoencephalitis.…”