Harpers

490 / CHAPTER 45FMN. The main dietary sources of riboflavin are milkand dairy products. In addition, because of its intenseyellow color, riboflavin is widely used as a food additive.Flavin Coenzymes Are Electron Carriersin Oxidoreduction ReactionsThese include the mitochondrial respiratory chain, keyenzymes in fatty acid and amino acid oxidation, andthe citric acid cycle. Reoxidation of the reduced flavinin oxygenases and mixed-function oxidases proceeds byway of formation of the flavin radical and flavin hydroperoxide,with the intermediate generation of superoxideand perhydroxyl radicals and hydrogen peroxide.Because of this, flavin oxidases make a significant contributionto the total oxidant stress of the body.Riboflavin Deficiency IsWidespread But Not FatalAlthough riboflavin is fundamentally involved in metabolism,and deficiencies are found in most countries,it is not fatal as there is very efficient conservation oftissue riboflavin. Riboflavin deficiency is characterizedby cheilosis, lingual desquamation and a seborrheic dermatitis.Riboflavin nutritional status is assessed by measurementof the activation of erythrocyte glutathionereductase by FAD added in vitro.NIACIN IS NOT STRICTLY A VITAMINNiacin was discovered as a nutrient during studies of pellagra.It is not strictly a vitamin since it can be synthesizedin the body from the essential amino acidtryptophan. Two compounds, nicotinic acid and nicotinamide,have the biologic activity of niacin; its metabolicfunction is as the nicotinamide ring of the coenzymesNAD and NADP in oxidation-reduction reactions(Figure 45–11). About 60 mg of tryptophan is equivalentto 1 mg of dietary niacin. The niacin content of foods isexpressed as mg niacin equivalents = mg preformed niacin+ 1/60 × mg tryptophan. Because most of the niacin incereals is biologically unavailable, this is discounted.NAD Is the Source of ADP-RiboseIn addition to its coenzyme role, NAD is the source ofADP-ribose for the ADP-ribosylation of proteins andpolyADP-ribosylation of nucleoproteins involved in theDNA repair mechanism.Pellagra Is Caused by Deficiencyof Tryptophan & NiacinPellagra is characterized by a photosensitive dermatitis.As the condition progresses, there is dementia, possibly+NCONH 2OH OHOCH 2NCOONicotinic acidO OO P O P OO ONADOH OHdiarrhea, and, if untreated, death. Although the nutritionaletiology of pellagra is well established and tryptophanor niacin will prevent or cure the disease, additionalfactors, including deficiency of riboflavin orvitamin B 6 , both of which are required for synthesis ofnicotinamide from tryptophan, may be important. Inmost outbreaks of pellagra twice as many women asmen are affected, probably the result of inhibition oftryptophan metabolism by estrogen metabolites.Pellagra Can Occur as a Resultof Disease Despite an AdequateIntake of Tryptophan & NiacinA number of genetic diseases that result in defects oftryptophan metabolism are associated with the developmentof pellagra despite an apparently adequate intakeof both tryptophan and niacin. Hartnup disease is arare genetic condition in which there is a defect of themembrane transport mechanism for tryptophan, resultingin large losses due to intestinal malabsorption andfailure of the renal resorption mechanism. In carcinoidsyndrome there is metastasis of a primary liver tumorof enterochromaffin cells which synthesize 5-hydroxytryptamine.Overproduction of 5-hydroxytryptaminemay account for as much as 60% of the body’s tryptophanmetabolism, causing pellagra because of the diversionaway from NAD synthesis.Niacin Is Toxic in ExcessNicotinic acid has been used to treat hyperlipidemiawhen of the order of 1–6 g/d are required, causing dilationof blood vessels and flushing, with skin irritation.Intakes of both nicotinic acid and nicotinamide in excessof 500 mg/d can cause liver damage.NNicotinamideNNNNCH 2NH 2OCONH 2Figure 45–11. Niacin (nicotinic acid and nicotinamide)and nicotinamide adenine dinucleotide (NAD).* Shows the site of phosphorylation in NADP.