FMN

**Structure and synthesis** - Riboflavin (vitamin B2) + ATP → FMN via riboflavin kinase (requires ATP; thyroid hormone upregulates this step). - FMN + ATP → FAD via FAD synthetase. - FMN is riboflavin-5'-phosphate. It is not a true nucleotide because it has a ribitol sugar alcohol rather than ribose.

**Biochemical function** - Redox cofactor: accepts 2 electrons and 2 H+ to become FMNH2 (fully reduced). It can also form a semiquinone (FMNH•), so it can bridge 2-electron and 1-electron transfers. - Complex I (NADH-ubiquinone oxidoreductase) of the ETC: NADH donates electrons to FMN, which passes them to Fe-S clusters and then to coenzyme Q (ubiquinone). This is coupled to proton pumping (4 H+) into the intermembrane space. - FAD is used by succinate dehydrogenase (Complex II), α-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and acyl-CoA dehydrogenase. FMN is used by Complex I, L-amino acid oxidase, and pyridoxine (pyridoxamine) 5'-phosphate oxidase, which activates B6.

**Clinical significance** - Riboflavin deficiency (ariboflavinosis) causes the "2 C's and 2 S's": cheilosis, corneal vascularization, stomatitis, and seborrheic dermatitis. It can also cause angular stomatitis, glossitis (magenta tongue), and normocytic anemia. - Causes include alcoholism, malabsorption, and phototherapy in neonates (riboflavin is light-sensitive). - Riboflavin (B2) is a cofactor for flavoproteins in redox reactions. Mnemonic: "FAD and FMN are derived from riboflavin (B2 = 2 ATP)". FAD formation requires 2 ATP, and FMN formation requires 1 ATP. - Riboflavin supplementation is used in migraine prophylaxis. Riboflavin is also used in multiple acyl-CoA dehydrogenase deficiency (MADD). - Urine turns bright yellow-orange with supplementation. - Complex I inhibitors that block electron flow from FMN/Fe-S to CoQ: rotenone, amytal (amobarbital), and MPP+ (the active metabolite of MPTP, linked to parkinsonism). Cyanide, CO, and azide inhibit Complex IV. Antimycin A inhibits Complex III. Oligomycin inhibits ATP synthase (Complex V). - Leber hereditary optic neuropathy (mitochondrial inheritance) involves Complex I mutations (commonly MT-ND4, MT-ND1, MT-ND6).

**Other meanings (avoid confusion)** - FMN can also mean "fibromuscular network" or "frontal midline..." but on USMLE it nearly always means flavin mononucleotide.

**High-yield takeaway** Riboflavin (B2) → FMN (1 ATP) → FAD (2nd ATP). FMN is the first electron acceptor of Complex I, which accepts electrons from NADH.