Involved in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 6 of the fatty acyl chain. Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively (PubMed:12713571). Subsequently, in the biosynthetic pathway of HUFA n-3 series, it desaturates tetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3), which is then converted to docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system function (By similarity). Desaturates hexadecanate (palmitate) to produce 6Z-hexadecenoate (sapienate), a fatty acid unique to humans and major component of human sebum, that has been implicated in the development of acne and may have potent antibacterial activity (PubMed:12713571). It can also desaturate (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 6 generating (6Z,11E)-octadecadienoate (By similarity). In addition to Delta-6 activity, this enzyme exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA substrates (By similarity). (9Z,12Z)-octadecadienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (6Z,9Z,12Z)-octadecatrienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (9Z,12Z,15Z)-octadecatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O 2 Fe(II)-[cytochrome b5] + 2 H(+) + hexadecanoyl-CoA + O2 = (6Z)-hexadecenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (6Z,11E)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (11Z,14Z)-eicosadienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (8Z,11Z,14Z)-eicosatrienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (11Z,14Z,17Z)-eicosatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = (8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O Lipid metabolism; polyunsaturated fatty acid biosynthesis. Expressed in a wide array of tissues, highest expression is found in liver followed by brain, lung, heart, and retina. A lower level is found in breast tumor when compared with normal tissues; lowest levels were found in patients with poor prognostic index. Found in fetal heart. Repressed by dietary highly unsaturated fatty acids. The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes HXXXH, HXXHH, and QXXHH (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases. Belongs to the fatty acid desaturase type 1 family.