NADH cytochrome b5 reductase 3 (B5R, diaphorase-1, CYB5R3, DIA1)

Function

• desaturation & elongation of fatty acids
• cholesterol biosynthesis
• drug metabolism
• in erythrocyte, methemoglobin reduction
• component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) & MOSC2 (putative)
• microsomal electron transport system

NADH + 2 ferricytochrome b5 <--> NAD+ + H+ + 2 ferrocytochrome b5

Cofactor: FAD

Structure

• belongs to the flavoprotein pyridine nucleotide cytochrome reductase family

Compartment

• isoform 1:
  • endoplasmic reticulum membrane lipid-anchor,cytoplasmic side
  • mitochondrion outer membrane lipid-anchor, cytoplasmic side
• isoform 2: cytoplasm, produces soluble form found in erythrocytes Alternative promoter:
• named isoforms=2

Expression

• isoform 2 (soluble form) is expressed at late stages of erythroid maturation

Pathology

• defects in CYB5R3 are the cause of hereditary methemoglobinemia

Polymorphism

• Ser-117 seems to only be found in persons of African origin, allele frequency is 0.23 in African Americans, not found in Caucasians, Asians, Indo-Aryans, or Arabs, no effect on the enzyme activity

More general terms

• NADH cytochrome b5 reductase; NADH-methemoglobin reductase
• myristoylated protein
• phosphoprotein

Database

• UniProt: http://www.uniprot.org/uniprot/P00387.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1727
• OMIM: https://mirror.omim.org/entry/250800