vitamin b 2 : riboflavin karilyne manahan & alyssa specht
TRANSCRIPT
Chemical Name and Structure
● Riboflavin also known as vitamin B2 and is an essential water-
soluble 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)
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
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
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
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
References1. Powers H. Riboflavin (vitamin B2) and health. AM J Clin Nutr. 2003; 77:1352-60.2. Gropper S, Smith J. Advanced Nutrition and Human Metabolism. 6th ed. Belmont, CA: Wadsworth CENGAGE Learning; 2013. 3. 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/ 4. Wang G, Li W, Zhao X. Riboflavin alleviates cardiac failure in type I diabetic cardiomyopathy. Heart Int [Internet]. 2011; 6(21): 75-
79. 5. 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.1755-5949.2012.00379.x/full 6. 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. 7. 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.
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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.
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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
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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.