Year-end Sale % OFF 
Abstract
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.
Highlights
Tracer purity The 2H5-Tetracosahexaenoic acid (THA) infusate and the 2H5-ALA + 13C22-DHA infusate were assessed by GC/MS for contaminant isotopes that would result in false-positive determinations of the origin of n-3 PUFA metabolites, with representative chromatograms presented (Fig. 1)
In the 2H5-ALA + 13C22-DHA infusate (Fig. 1B), no 13C20-22-n-3 PUFA contaminants were detected for EPA, n-3 docosapentaenoic acid (DPAn-3), n-3 tetracosapentaenoic acid (TPAn-3), or THA, with 13C22-DHA being the only 13C-n-3 PUFA identified
In the 2H5-THA infusate (Fig. 1C), no 2H5-n-3 PUFA contaminants were detected for ALA, EPA, DPAn-3, DHA, or TPAn-3
Summary
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. A lack of labeled DHA accumulation in Zellweger’s patients [2, 3] signaled a role for the peroxisomes in the -oxidation of THA to DHA, following the elongation and subsequent 6desaturation of DPAn-3 to n-3 tetracosapentaenoic acid (TPAn-3; 22:5n-3) and THA, respectively. The human cell study demonstrated that in the absence of functional 6-desaturase activity, labeled DPAn-3 could be converted directly to DHA [5]; it is possible that this 4-desaturase activity is upregulated in response to the absence of a 6desaturase enzyme
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
