Abstract
Creatine stores high-energy phosphate bonds in muscle and is synthesized in the liver through methylation of guanidinoacetic acid (GAA). Supplementation of GAA may therefore increase methyl group requirements, and this may affect methyl group utilization. Our experiment evaluated the metabolic responses of growing cattle to postruminal supplementation of GAA, in a model where methionine (Met) was deficient, with and without Met supplementation. Seven ruminally cannulated Holstein steers (161 kg initial body weight [BW]) were limit-fed a soybean hull-based diet (2.7 kg/d dry matter) and received continuous abomasal infusions of an essential amino acid (AA) mixture devoid of Met to ensure that no AA besides Met limited animal performance. To provide energy without increasing the microbial protein supply, all steers received ruminal infusions of 200 g/d acetic acid, 200 g/d propionic acid, and 50 g/d butyric acid, as well as abomasal infusions of 300 g/d glucose. Treatments, provided abomasally, were arranged as a 2 × 3 factorial in a split-plot design, and included 0 or 6 g/d of l-Met and 0, 7.5, and 15 g/d of GAA. The experiment included six 10-d periods. Whole body Met flux was measured using continuous jugular infusion of 1-13C-l-Met and methyl-2H3-l-Met. Nitrogen retention was elevated by Met supplementation (P < 0.01). Supplementation with GAA tended to increase N retention when it was supplemented along with Met, but not when it was supplemented without Met. Supplementing GAA linearly increased plasma concentrations of GAA and creatine (P < 0.001), but treatments did not affect urinary excretion of GAA, creatine, or creatinine. Supplementation with Met decreased plasma homocysteine (P < 0.01). Supplementation of GAA tended (P = 0.10) to increase plasma homocysteine when no Met was supplemented, but not when 6 g/d Met was provided. Protein synthesis and protein degradation were both increased by GAA supplementation when no Met was supplemented, but decreased by GAA supplementation when 6 g/d Met were provided. Loss of Met through transsulfuration was increased by Met supplementation, whereas synthesis of Met from remethylation of homocysteine was decreased by Met supplementation. No differences in transmethylation, transsulfuration, or remethylation reactions were observed in response to GAA supplementation. The administration of GAA, when methyl groups are not limiting, has the potential to improve lean tissue deposition and cattle growth.
Molecular docking and density functional theory studies on creatine, guanidinoacetic acid, and their phosphorylated analogues binding to muscle creatine kinase