Characterizing the effects of creatine precursors, guanidinoacetic acid (GAA) and methionine on creatine absorption using an in vitro model

Adar Buxton
MSc Student
Department of Biochemistry

Date: September 23, 2024
Time: 1:00 p.m. to 2:00 p.m. 
Room: CSF 1302

Abstract:

Among the many important roles in neonatal development, creatine also functions as a high-energy buffer in cells with a high energy demand. During acute movements and brain activity, these cells temporarily use creatine phosphate to supply inorganic phosphate for the regeneration of ATP. Creatine can be supplemented, or endogenously synthesized from GAA and methionine.
Despite the increasing popularity of creatine supplementation, creatine absorption is limited due to poor solubility and low absorption rates. Studies have shown that klotho, 4-hydroxyisoleucine & carbohydrates have the ability to upregulate creatine absorption, thereby improving bioavailability despite poor solubility. Results from recent studies in our lab indicate that creatine, methionine, and GAA absorption are interdependent in the gut. Using a human intestinal Caco-2 cell line as an in vitro model, we hypothesized that a creatine:methionine:GAA combination (1:4:1) will upregulate creatine transport more than methionine or GAA alone.
Preliminary results showed that GAA may have an inhibitory effect on the transport of creatine. Interestingly, transport across the basolateral (serosal) membrane appears to be enhanced by the presence of GAA while transport across the brush border (lumen) membrane appears to be inhibited by the presence of GAA. Further experiments to deduce the ratio of GAA having the most inhibitory effect on creatine transport have also been carried out. Experiments are underway to isolate primary cells from fast-twitch muscle tissue in Yucatan miniature piglets. The isolated cells will be used to study the inhibitory effects of GAA on the absorption of creatine in cells with a high-energy demand such as skeletal muscle (Funding provided by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada).