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Balasubramaniam et al. J Transl Genet Genom 2020;4:285-306  I  http://dx.doi.org/10.20517/jtgg.2020.34                  Page 287

















































               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
                             [5]
                                                     [3]
               (see also Barile et al.  2016 and Balasubramaniam et al.  2019). FAD: flavin adenine dinucleotide; FMN: flavin mononucleotide; FADT:
               flavin adenine dinucleotide transporter
               MITOCHONDRIA-THE CELL’S POWERHOUSE
               Mitochondria are maternally inherited multifunctional double-membrane, highly dynamic cytoplasmic
               organelles, ubiquitously present in all cells, except erythrocytes. The mitochondrion is composed of several
               compartments that carry out specialized functions. These include the outer membrane, inner membrane,
               the intermembrane space, and cristae, which are the in-folding of the inner membrane and matrix.
               Mitochondria execute myriad vital cellular processes including fatty acid oxidation, urea cycle, Krebs cycle,
               biosynthesis of heme and steroids, maintenance of calcium homeostasis, caspase-dependent apoptosis,
               reactive oxidant species (ROS) generation, and heme and steroid synthesis [12,13] . In addition to these
               functions, the hallmark of mitochondria is the pivotal role it plays in aerobic cellular energy generation via
               oxidative phosphorylation (OXPHOS).
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