Docosahexaenoic acid is both a product of and a precursor to tetracosahexaenoic acid in the rat[S]

• Main Authors: Adam H. Metherel, R. J. Scott Lacombe, Raphaël Chouinard-Watkins, Richard P. Bazinet
• Format: Article
• Language: English
• Published: Elsevier 2019-02-01
• Series: Journal of Lipid Research
• Subjects: synthesis-secretion; Sprecher pathway; kinetics; fatty acid/metabolism; fatty acid/biosynthesis; omega-3 fatty acids
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520326523

Tetracosahexaeoic acid (THA; 24:6n-3) is thought to be the immediate precursor of DHA in rodents; however, the relationship between THA and DHA metabolism has not been assessed in vivo. Here, we infused unesterified 2H5-THA and 13C22-DHA, at a steady state, into two groups of male Long-Evans rats and determined the synthesis-secretion kinetics, including daily synthesis-secretion rates of all 20-24 carbon n-3 PUFAs. We determined that the synthesis-secretion coefficient (a measure of the capacity to synthesize a given fatty acid) for the synthesis of DHA from plasma unesterified THA to be 134-fold higher than for THA from DHA. However, when considering the significantly higher endogenous plasma unesterified DHA pool, the daily synthesis-secretion rates were only 7-fold higher for DHA synthesis from THA (96.3 ± 31.3 nmol/d) compared with that for THA synthesis from DHA (11.4 ± 4.1 nmol/d). Furthermore, plasma unesterified THA was converted to DHA and secreted into the plasma at a 2.5-fold faster rate than remaining as THA itself (26.2 ± 6.3 nmol/d), supporting THA's primary role as a precursor to DHA. In conclusion, using a 3 h infusion model in rats, we demonstrate for the first time in vivo that DHA is both a product and a precursor to THA.