Methionine and guanidinoacetic acid metabolism in Yucatan miniature piglets

Asiriwardhana, Mahesha (2025) Methionine and guanidinoacetic acid metabolism in Yucatan miniature piglets. Doctoral (PhD) thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (2MB)

Abstract

Methionine, an essential amino acid, plays crucial roles beyond its incorporation into proteins. It can be converted into S-adenosylmethionine (SAM), the universal methyl donor involved in over 50 transmethylation reactions. These reactions are essential for creatine and phosphatidylcholine (PC) synthesis and DNA methylation. The first experiment in this thesis investigated the methionine requirement for synthesizing major transmethylated products, whole body proteins and tissue specific proteins. Data from the first experiment demonstrated that DNA methylation is prioritized over hepatic creatine synthesis, while PC synthesis continuously increases with methionine intake. When methionine was limited, liver protein synthesis was prioritized, followed by kidney and muscle protein synthesis. Since different tissues have varying methionine requirements, our data provide insights into why growth is restricted at lower amino acid intakes, to spare limited amino acids for intestinal function and critical metabolic processes in other vital organs.. These findings indicate that using protein synthesis alone to determine whole-body methionine requirements is inadequate, as more methionine is needed to fulfill its non-protein roles. The second major objective of this thesis was to investigate the effect of dietary methionine on supplemental guanidinoacetate (GAA) absorption and creatine synthesis in neonatal piglets. Using a 4-h duodenal infusion with radioisotope tracers and dietary treatments varying in methionine levels, we found that excess dietary methionine increases the portal appearance of GAA and enhances creatine synthesis in piglets. Furthermore, our data revealed that GAA accumulates in the liver when dietary methionine is deficient, although no toxic effect was apparent. Recently, researchers identified that the GAA + creatine mixture enhanced muscle and brain creatine levels in healthy individuals. However, there is little information on how the GAA + creatine mixture affects GAA absorption, transport, and utilization in pigs. Hence, we compared the effectiveness of three supplementation options: GAA alone, GAA + methionine, and GAA + creatine, in enhancing creatine stores and GAA absorption in neonatal piglets. Moreover, we evaluated the effectiveness of creatine and GAA combinations in enhancing GAA absorption across the gut in neonatal piglets using an ex vivo Ussing chamber model. This study demonstrated that both GAA + methionine and GAA + creatine groups showed increased brain creatine levels, compared to control. Moreover, hepatic creatine concentration was highest in the GAA + creatine group, compared to control and GAA groups, suggesting GAA+ creatine is the best combination to improve hepatic creatine stores. Findings from the Ussing chamber model showed that a higher level of creatine enhanced GAA absorption across the jejunum. Overall, these studies improve our understanding of methionine metabolism in both protein and non-protein pathways and GAA metabolism and creatine synthesis in neonatal piglets. These findings could significantly impact the animal industry and health and disease management across various populations, including different age groups and animal species.

Actions (login required)

View Item