fig1

Figure 1. Metabolism and transport of riboflavin and flavocoenzyme. Dietary FAD and FMN are converted to riboflavin by non-specific hydrolases on the brush-border membrane of ileal enterocytes and are subsequently absorbed into the intestine via apically expressed RFVT3. Inside the enterocytes, riboflavin can either be further metabolized to FMN by riboflavin kinase and subsequently to FAD by FAD synthase or released into portal blood by basolaterally expressed RFVT1 and RFVT2. Circulating plasma riboflavin associates with albumin or globulins or is converted into a coenzyme form in erythrocytes or leukocytes. RFVT2-mediated transport allows riboflavin uptake into the brain where it is highly expressed, and additionally into endocrine organs, such as pancreas, liver, and muscle tissue. The mechanism of import of riboflavin into the mitochondrial matrix has not been precisely elucidated to date. “RFVT?” is depicted as a putative riboflavin transporter responsible for this step. The mitochondrial FADT imports FAD from the cytosol into the mitochondria. The question mark indicates that FADT-mediated efflux of FAD from the mitochondrial matrix to the cytosol remains to be established (see also Barile et al.^[5] 2016 and Balasubramaniam et al.^[3] 2019). FAD: flavin adenine dinucleotide; FMN: flavin mononucleotide; FADT: flavin adenine dinucleotide transporter