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Evidence that liver microsomes of human neonates desaturate essential fatty acids
J P Poisson1, R P Dupuy, P Sarda
1Unité de Recherche de Nutrition Cellulaire et Métabolique, Université de Bourgogne, Faculté des Sciences Mirande, Dijon, France.
Insights
Newborns possess essential delta 6- and delta 5-desaturase activities for polyunsaturated fatty acids (PUFAs) synthesis, crucial for brain development. However, these enzyme activities are lower in neonates compared to adults.
Area of Science:
- Biochemistry
- Human Physiology
- Perinatal Medicine
Background:
- Polyunsaturated fatty acids (PUFAs) are vital for cellular function and development.
- Essential fatty acid desaturation via delta 6- and delta 5-desaturase is critical for PUFA biosynthesis.
- PUFA accretion is particularly active in the developing central nervous system during the perinatal period.
Purpose of the Study:
- To investigate the presence and activity of delta 6- and delta 5-desaturase enzymes in human neonates.
- To quantify these desaturase activities in newborn liver microsomes.
- To compare neonatal desaturase activity with that reported in adult humans and other mammals.
Main Methods:
- Utilized radiochemical assays to measure delta 6- and delta 5-desaturase activities.
- Employed reverse-phase High-Performance Liquid Chromatography (HPLC) for product analysis.
- Analyzed enzyme kinetics in liver microsomes from three human neonates.
Main Results:
- Detected significant delta 6- and delta 5-desaturase activities in human neonatal liver microsomes.
- Quantified n-6 series activities: delta 6-desaturase (4.8–13.6 pmol/min/mg) and delta 5-desaturase (3.2–16.4 pmol/min/mg).
- Quantified n-3 series delta 6-desaturase activity (5.3–12.8 pmol/min/mg), noting potential substrate inhibition for n-6 fatty acids.
Conclusions:
- Human neonates exhibit functional delta 6- and delta 5-desaturase activities.
- Neonatal desaturase activity is lower than reported in adult humans and mammals, especially rodents.
- These findings highlight potential differences in PUFA metabolism during early development.
Abstract:
delta 6- and delta 5-Desaturation of essential fatty acids of n-6 and n-3 series are required for the biosynthesis of polyunsaturated fatty acids (PUFAs), which are precursors of eicosanoids and constituents of membrane phospholipids. This pathway could be of special importance during the perinatal period, when PUFAs accretion in the central nervous system is very active. However, experimental evidence of delta 6- and delta 5-desaturase activities in man is very scarce, and no data are available for newborns. We report the delta 6- and delta 5-desaturase activities detected in human liver microsomes from three neonates who died from associated malformations. Radiochemical assays of delta 6- and delta 5-desaturase activities performed with reverse phase HPLC analysis of the products in the n-6 series ranged from 4.8-13.6 to 3.2-16.4 pmol substrate converted.min-1.mg-1 microsomal proteins, respectively. In the n-3 series delta 6-desaturase activity ranged from 5.3 to 12.8 pmol.min-1.mg-1. The relationships between enzyme activities and substrate concentrations suggest excess substrate inhibition for n-6 and not for n-3 fatty acids. These results demonstrate significant delta 6- and delta 5-desaturase activities in human liver of neonates, but this activity was lower than previously reported in adult humans and in mammals, especially rodents.