**2. DHA Biochemistry**

DHA belongs to the family of fatty acids (FA) which are divided into distinct families according to the amount of carbon they contain and the presence or absence of unsaturations in their hydrocarbon chain (Figure 1) (see review [8]). Thus, we find saturated fatty acids (SFA) that have no double bond, the most common of which are palmitic acid (C16:0) and stearic acid (C18:0). Then, the presence of a single double bond in the carbon chain qualifies the fatty acid as monounsaturated (MUFA); this is the case for oleic acid (C18:1 omega-9). Finally, from two double bonds, we have polyunsaturated fatty acids (PUFA). This last family is divided into two subfamilies: the omega-6 family and the omega-3 family, which are distinguished by the position of the first double bond carried, respectively, by the sixth (n-6 or ω6) or third carbon (n-3 or ω3) from the terminal methyl end. PUFAs 6 and 3 (C20 and C22) are derived from two indispensable precursors, respectively: linoleic acid and α-linolenic acid (consisting of 18 carbon atoms and 3 double bonds).

**Figure 1.** The different families of fatty acids and their main members. Fatty acids are classified according to the saturation or unsaturation of the carbon chain. There are saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA). Among the latter, we distinguish between omega-3 and omega-6. Docosahexaenoic acid belongs to the omega-3 family.

DHA is a major component of PUFAs in all cell membranes. It is necessary for proper development of the retina and the central nervous system (CNS) [9]. DHA deficiency disrupts the composition membrane lipid and thus the functions of astrocytes at the CNS level [10]. DHA is synthesized in the organism from essential precursors (α-linolenic acid C18:3 ω-3) provided by food [11]. The formation of DHA involves a succession of desaturations and elongations, which take place mainly in the liver, muscles, or even adipose tissue (Figure 2) [12]. DHA is synthesized from α-linolenic acid by two steps: conversion of C18:3 ω-3 to C20:5 ω-3 (eicosapentaenoic acid) then to C22:5 ω-3 (docosapentaenoic acid) and finally to C24:5 ω-3 (tetracosapentaenoic acid) in the endoplasmic reticulum. The second step consists of a single-ring peroxisomal β-oxidation of C24:6 ω-3 to C22:6 ω-3 (DHA) [13]. This step of peroxisomal β-oxidation requires the intervention of straight-chain acyl-CoA oxidase (SCOX), D-bifunctional protein (DBP), 3-ketoacyl-CoA thiolase, and sterol carrier protein (SCPx).

**Figure 2.** Biochemical pathway of DHA biosynthesis. In the endoplasmic reticulum, α-linolenic acid is converted to tetracosahexaenoic acid by the action of elongases and desaturases. Then, in the peroxisome (yellow arrow: electron microscopy of C2C12 myoblasts; provided by Imen Ghzaiel, PhD student), β-oxidation occurs and leads to the synthesis of DHA.
