Quantifying the effectiveness of dietary precursors on creatine synthesis in Yucatan miniature piglets

Cole Winsor
MSc Student
Department of Biochemistry

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

Abstract:

Neonatal development requires a surplus of creatine to accommodate rapidly growing tissue. We have shown that ~75% of creatine is synthesized in neonatal piglets. When producing creatine, arginine is first used to make guanidinoacetate (GAA), which is then methylated by methionine. Arginine is either consumed in the diet or endogenously synthesized via citrulline. We have shown that higher blood citrulline produced more GAA in the kidneys, the primary site of GAA synthesis, than arginine. Moreover, GAA is an effective precursor, but only when sufficient methionine is supplemented. We tested whether these observations will be true when feeding these precursors in the diet. Yucatan miniature piglets (17–22 d old; n=40) were fed an elemental, complete diet plus: 1) +Alanine (control), 2) +Creatine, 3) +Citrulline, 4) +Arginine, 5) +GAA; all diets contained excess methionine. Creatine synthesis was measured using 3H-methyl-methionine infusions. Preliminary data showed that muscle creatine concentration and creatine specific radioactivity were highest in +Citrulline piglets. Together, these results suggest that citrulline may be the most effective precursor to increase creatine production in neonatal piglets. Further analyses into other tissues (liver, brain, jejunum) will allow a more comprehensive analysis of creatine synthesis from various precursors. Additionally, we can isolate the key organs involved in creatine synthesis by analyzing trans-organ balance across liver, muscle, brain, and kidney. In summary, because neonates must synthesize at least 75% of their required creatine from the essential amino acids arginine and methionine, the provision of alternate precursors could be necessary to meet the creatine requirement, especially if creatine-free diets (e.g. soy-based formula) are used. Accommodating creatine synthesis using alternate precursors will also spare essential amino acids for protein and growth. (Funding provided by Natural Sciences and Engineering Research Council of Canada).