Transmembrane ascorbate-dependent reductase cytochrome b561 (CYB561)

Transmembrane ascorbate-dependent reductase cytochrome b561 (CYB561) is a multipass transmembrane enzyme that functions as an electron transporter, predominantly located in the membranes of secretory vesicles, such as chromaffin granules in neuroendocrine tissues[1][2][3]. This protein is involved in the transfer of electrons from cytosolic ascorbate (vitamin C) to intravesicular substrates, including iron (ferric chelates) and peptide-processing enzymes, thereby enabling enzymatic activities essential for neurotransmitter and peptide hormone biosynthesis (e.g., dopamine to norepinephrine conversion via dopamine-beta-hydroxylase)[1][2][3]. Structurally, it is composed of 273 amino acids with six transmembrane domains and two non-covalently bound heme groups that mediate electron transport[1][2][3]. CYB561 represents a distinct family of eukaryotic electron transfer enzymes and plays a key role in ascorbate recycling and iron absorption[3]. It is highly expressed in nervous and neuroendocrine tissues, such as the adrenal medulla and brain, but not in most peripheral organs[2]. No drugs are currently known to specifically target this protein, and no safety concerns or clinical biomarkers have been established for CYB561 as of current knowledge.

Other names

Transmembrane ascorbate-dependent reductase CYB561ferric-chelate reductase 2chromaffin granule cytochrome b561CGCytbcytochrome b-561cytochrome b561 family member A1FRRS2CYB561A1ORTHYP2

Substrate-mediated electron transfer from ascorbate to membrane-bound heme groups; Reduction of intravesicular ferric iron (Fe³⁺) to ferrous iron (Fe²⁺); Supply of reducing equivalents to enzymes (dopamine-beta-hydroxylase, peptide amidase)