Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Basal metabolic rate wikipedia , lookup
Biosynthesis wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Oxidative phosphorylation wikipedia , lookup
Biochemistry wikipedia , lookup
Citric acid cycle wikipedia , lookup
Metabolic network modelling wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Vitamin B2: Riboflavin Karilyne Manahan & Alyssa Specht Chemical Name and Structure ● Riboflavin also known as vitamin B2 and is an essential watersoluble vitamin ● Chemical name: 7,8-dimethyl-10-ribityl-isoalloxazine1 ● Chemical formula: C17H20N4O6 2 ● Composed from 3 ring structure call flavin and 5 carbon chain sugar alcohol named ribitol2 ○ Gets name ribo-flavin Major Coenzymes2 ● Two coenzymes derived from B2 ○ Flavin mononucleotide (FMN) ○ Flavin adenine dinucleotide (FAD) ● Formed by enzymes and composed of riboflavin and phosphate group (FMN) ● FAD further adds additional adenosine phosphate group (AMP) (2) Chief Functions2 ● Coenzymes FMN and FAD involved in several intermediary reactions involving flavoproteins ● Flavoproteins - enzymes requiring FMN or FAD as coenzymes ● Specifically in oxidation-reduction (redox) reactions Redox Reactions2 ● Essential for energy production by catabolizing carbohydrates, fats, and lipids to generate ATP by transferring electrons ● Flavins act as oxidizing agents by accepting 2 hydrogen atoms and losing 2 elections ● FMN and FAD reduced to FMNH2 and FADH2 Reducing of FMN or FAD2 FAD Reactions - Energy Production2 ● Metabolic pathways involved in: ○ Pyruvate Dehydrogenase Complex ○ Fatty Acid Beta-Oxidation ■ acyl-CoA dehydrogenase ○ Citric Acid Cycle ■ α-ketoglutarate dehydrogenase and succinate dehydrogenase enzyme pathways ○ Complex II of Electron Transport Chain (ETC) ○ FADH2 converted to ATP in ETC (1.5 ATP) FAD Reactions - Coenzyme Synthesis ● B3 from tryptophan2 ○ Kyrureninase monooxygenase ● Antioxidants3 ○ Xanthine oxidase to produce uric acid ○ Glutathione reductase to produce glutathione ● Converts folate to active form2 Continue ● aldehydes → carboxylic acids (aldehyde oxidase)2 ○ B6 → pyriodoxic acid ○ Retinol → retinoic acid FMN Reactions2 ● Energy production reactions ○ Complex I rxns in ETC ● Synthesis reactions ○ Formation of coenzyme form of B6 (pyridoxal phosphate or PLP) ■ pyridoxine phosphate oxidase Chief Functions: Disease Prevention and Treatment ● Protective against diseases with root cause from oxidative stress and inflammation ○ Cardioprotection4 ○ Neuroprotection ■ Stoke5 and Migraine Treatment(6,7) ○ Cancer Inhibition(1,2,8) ■ metabolize carcinogens Metabolic Pathways Bioavailability ● Riboflavin is not created or stored in the body9 must be consumed through diet ● Mostly found as FAD form in foods; lesser amount FMN1 and little “free” riboflavin in foods10 ● Must be converted to free riboflavin for absorption if bonded to proteins or if in FAD or FMN form2 ● If bond to histidine or cysteine cannot be converted2 Digestion2 ● Starts in stomach ○ Riboflavin-protein compounds → free riboflavin by hydrochloric acid ● Then small intestine ○ FAD → FMN → free riboflavin at brush border (intestinal phosphatases) Absorption ● Once in free form can be absorbed2 ● Major absorption site - proximal small intestine2 ● Occurs through carrier mediated1 sodium-independent active transport2 ● Per meal ~95% of riboflavin is absorbed2 ○ Max ~25mg Metabolism & Transport2 ● Quickly upon absorption into intestinal cell riboflavin → FMN (enzyme flavokinase) **Requires ATP** ● At serosal membrane FMN → riboflavin - - > portal vein - - > liver - - > tissues Metabolism & Transport2 ● Flavins in blood mostly found as riboflavin (50%) with some FAD (40%) and FMN (10%) ● FAD and FMN transported with protein carriers ○ albumin (primarily), fibrinogen, and globulins ● Once transported to tissue absorbed by a carrier-mediated riboflavin-binding protein ● High concentration enter by diffusion Metabolism & Transport10 ● In tissues: riboflavin → FMN ○ same process as earlier ● Further FMN → FAD (enzyme FAD synthetase) **Requires ATP** ● Phosphatases in tissue can convert back flavins back to riboflavin (2) Excretion ● Excreted through urine2 ● Small amounts stored in ○ liver, spleen, sm intestine,kidneys, and heart2 ● Can meet body’s needs for 2-6 weeks2 ● Protects against toxicity9 Daily Recommended Intake • Glutathione reductase an adequate indicator of riboflavin requirements as its processes2 o reduction of glutathione disulfide --> glutathione is dependent upon FAD and NADPH • Meeting the DRI is not a large issue in the United States due to it’s fortification of many grains and cereals(11,12) Daily Recommended Intake(1,2) Group Needs (mg/d) Men 1.3 Women 1.1 Pregnant/Lactating Women 1.4/1.6 Infants 0-6 months .3 Infants 6 months - 1 y .4 Children aged 1-3 y .5 Children aged 4-8 y .6 Deficiency • Ariboflavinosis (riboflavin disease in isolation) is rare o often in congruence with other vit./min. deficiencies(1,2) • Clinical Signs: o cheilosis, angular stomatitis, oral hyperemia, edema, seborrheic dermatitis, and neuropathy2 o Protein and DNA damage also possible due to GI phase of Cell cycle inhibited2 • Anemia, growth retardation, susceptibility to some carcinogens also possible2 Deficiency • Also related to B12 and folate deficiencies o Decreased riboflavin = ↓folate = ↓methionine → homocysteine (may ↑ CVD risk)1 o B12 derivative dependent on flavoproteins • Current treatment for riboflavin deficiency is 10-20 mg/d supplementation until symptoms are resolved1 • Other diseases that inc. risk of deficiency: o thyroid disease, DBM, chronic stress, depression, gastrointestinal diseases, cataracts(1,2) Deficiency • Populations at Risk o Pregnant/lactating women, infants, school-aged children, elderly, athletes, vegetarians/vegans, alcoholics, anorexics, third world country populations1 o Lactating women have estimated 40-90% increased needs12 o Infants treated for hyperbilirubinemia at risk due to phototherapy treatment1 Toxicity • The body is protected from riboflavin toxicity due to its ability to readily excrete excess levels in the urine • No tolerable upper level intake has been established1 Significant Sources • • Predominantly found as FAD in foods Milk and eggs have high amounts of free riboflavin2 o these and other dairy products are primary sources of riboflavin13 o • riboflavin in cow’s milk is 90% free form13 Grains provide up to 20% daily requirements as whole grains or fortified products14 • Meat, legumes, and dark leafy vegetables are good sources2 Negative Effects on Riboflavin Content ● Light has the biggest effect on riboflavin - up to 50% of riboflavin destroyed if held in light for only 2 hours3 ● Oxidation15 ○ Trolox & ascorbic acid can reduce by antioxidant mechanisms ● Fairly heat resistant, however pasteurization and UHT slightly lower levels13 Fortification & Additives ● These processes enrich riboflavin content in foods making them good sources ● Cost-effective way to increase riboflavin in foods → increase population intakes ● Fortification is highly used in grain products ● Additives, like improved lactic acid bacteria (LAB) strains added to yogurt to increase riboflavin synthesis16 References 1. 2. 3. 4. 5. 6. 7. 8. 9. Powers H. Riboflavin (vitamin B2) and health. AM J Clin Nutr. 2003; 77:1352-60. Gropper S, Smith J. Advanced Nutrition and Human Metabolism. 6th ed. Belmont, CA: Wadsworth CENGAGE Learning; 2013. Higdon J, Delage B, McNulty H, McCann A. Riboflavin. [Internet]. Oregon: Linus Pauling Institute. 2002 [2013]. Availible from: http://lpi.oregonstate.edu/infocenter/vitamins/riboflavin/ Wang G, Li W, Zhao X. Riboflavin alleviates cardiac failure in type I diabetic cardiomyopathy. Heart Int [Internet]. 2011; 6(21): 75-79. Zhou Y, Zhang X, Su F, Liu X. Importance of riboflavin kinase in the pathogenesis of stroke. CNS Neurosci Ther [Internet]. 2012 Oct 18(10):834-840. Available from Wiley Online Library: http://onlinelibrary.wiley.com/doi/10.1111/j.17555949.2012.00379.x/full MacLennan SC, Wade FM, Forrest KM, Ratanayake PD, Fagan E, Antony J. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol 2008;23(11):1300-4. Bruijn J, Duivenvoorden H, Passchier J, Locher H, Dijkstra N, Arts WF. Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial. Cephalalgia [Internet]. Mar 26 2010;30(12):1426-34. Sharp L, Carsin A, Cantwell M, Anderson L, Murray L. Intakes of dietary folate and other B vitamins are associated with risks of esophageal adenocarcinoma, barrett’s esophagus, and reflux esophagitis. J Nutr [Internet]. 2013 Dec [cited March 20, 2014] 143(12):1966-1973. Available from: http://nutrition.highwire.org/content/143/12/1966.short Subramanian V, Subramanya S, Ghosal A, Said H. Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport. American Journal Of Physiology: Cell Physiology [Internet]. 2013, Sep, [cited March 20, 2014];305(5):C539-C546. Available from: Academic Search Complete. References 10. Dey M, Mukherjee D, Dutta M, Mallik S, Ghosh D, Bandyopadhyay D. Flavin mono nucleotide phosphatase from goat heart: A forgotten enzyme of an important metabolic pathway. Journal Of Cell & Tissue Research [Internet]. 2013, Dec [cited March 20, 2014]; 13(3): 3851-3858. Available from: Academic Search Complete. 11. Feili Lo Y, Pei-Chun L, Yung-Ying C, Jui-Line W, Ning-Sing S. Prevalence of thiamin and riboflavin deficiency among the elderly in Taiwan. Asia Pacific Journal Of Clinical Nutrition [serial on the Internet]. 2005, Sept [cited March 20, 2014];14(3):238-243. Available from: Academic Search Complete. 12. Papathakis P, Pearson K. Food fortification improves the intake of all fortified nutrients, but fails to meet the estimated dietary requirements for vitamins A and B6, riboflavin and zinc, in lactating South African women. Public Health Nutrition [serial on the Internet]. 2012, Oct [cited March 20, 2014];15(10):1810-1817. Available from: Academic Search Complete. 13. Sunaric S, Denic M, Kocic G. Evaluation of riboflavin content in dairy products and non-dairy substitutes. Italian Journal Of Food Science [serial on the Internet]. (2012, Oct), [cited March 20, 2014]; 24(4): 352-357. Available from: Academic Search Complete. 14. Martinez-Villaluenga C, Michalska A, Frias J, Piskula M, Vidal-Valverde C, Zieliński H. Effect of Flour extraction rate and baking on thiamine and riboflavin content and antioxidant capacity of traditional rye bread. Journal Of Food Science [Internet]. (2009, Jan), [cited March 20, 2014];74(1):C49-C55. Available from: Academic Search Complete 15. Hall N, Chapman T, Kim H, Min D. Antioxidant mechanisms of Trolox and ascorbic acid on the oxidation of riboflavin in milk under light. Food Chemistry [Internet]. (2010, Feb), [cited March 20, 2014];118(3):534-539. Available from: Academic Search Complete. 16. Jayashree S, Rajendhran J, Jayaraman K, Kalaichelvan G, Gunasekaran P. Improvement of Riboflavin Production by Lactobacillus fermentum Isolated from Yogurt. Food Biotechnology [Internet]. 2011, July, [cited March 20, 2014]; 25(3): 240-251. Available from: Academic Search Complete.