Download Vitamin B2: Riboflavin

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.