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“B” Healthy B Vitamins

PHM142 Fall 2014 Instructor: Dr. Jeffrey Henderson. “B” Healthy B Vitamins. Corporate Managers Siddharth Bhalla Jennifer Lim Dianna Le Dana Shan. What are B vitamins?. A class of water-soluble vitamins that facilitate:

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“B” Healthy B Vitamins

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  1. PHM142 Fall 2014 Instructor: Dr. Jeffrey Henderson “B” HealthyB Vitamins Corporate Managers Siddharth Bhalla Jennifer Lim Dianna Le Dana Shan

  2. What are B vitamins? • A class of water-soluble vitamins that facilitate: • Physiological processes involved in making or extracting energy from food (metabolism) • RBC production • Cancer/disease prevention?

  3. What are B vitamins? • There are eight different types: • B1 (thiamine) • B2 (riboflavin) • B3 (niacin) • B5 (pantothenic acid) • B6 (pyridine derivatives) • B7 (biotin) • B9 (folic acid) • B12(cyanocobalamin)

  4. Vitamin B3 (niacin) BOS-1T8

  5. Niacin (nicotinic acid) niacin nicotinamide NAD+ NADP+

  6. General Function • Synthesis of fatty acids and cholesterol (NADH) • Hydrogen carriers for reactions catalyzed by dehydrogenase • Metabolism of carbohydrates, fats, proteins (NAD+) • In non-redox reactions, NAD+ is a substrate for mono-ADP-ribosyltransferases and poly-ADP-ribose polymerase • Cytochrome P450 reactions

  7. Sources

  8. Pharmacological applications

  9. Cholesterol: a review Image retrieved from www.clinbiochem.info

  10. Cholesterol: a review Cardiovascular diseases cost the Canadian economy more than $20.9 billion per year Stroke. Image retrieved from http://vascularsurgeon-ny.com/doctor/ Gu-Cheng et al., 2013

  11. Anti-hyperlipidemic • Improves lipid and cholesterol profile • Inhibits hydrolysis of triglycerides into free fatty acids • Inhibits de novo synthesis of triglycerides • Increases functional HDL • Slows and potentially reverses the progression of atherosclerosis

  12. Anti-hyperlipidemic • Improves lipid and cholesterol profile • Inhibits hydrolysis of triglycerides into free fatty acids • Inhibits de novo synthesis of triglycerides • Increases functional HDL • Slows and potentially reverses the progression of atherosclerosis

  13. Anti-hyperlipidemic BOS-1T8 Lukasova et al., 2011.

  14. Anti-hyperlipidemic • Improves lipid and cholesterol profile • Inhibits hydrolysis of triglycerides into free fatty acids • Inhibits de novo synthesis of triglycerides • Increases functional HDL • Slows and potentially reverses the progression of atherosclerosis

  15. Anti-hyperlipidemic HDL Peripheral Tissues LDL Elimination

  16. Anti-hyperlipidemic Leukocyte myeloperoxidase (MPO): H2O2 + Cl- → HOCl (potent microbicide) Marsche et al., 2001.

  17. Anti-hyperlipidemic Reduction in MPO activity attenuates HDL degradation and dysfunction Improves cholesterol clearance Ganji et al., 2014.

  18. Anti-atherothrombotic • Attenuates systemic inflammation • Improves endothelial dysfunction • Decrease in C-reactive protein • ↑ plaque stability → ↓ thrombosis

  19. Dose and side effects • Dose to achieve lipid modifying effects: • Minimal dose: 1 g/day • Greatest efficacy: 2 g/day • Side effects • Subcutaneous flushing • through GPCR109A • Deficiency • Pellagra: four “Ds” • Treat with nicotinamide

  20. “B” Healthy!

  21. References Antoniades C, Antonopoulos AS, Tousoulis D, Marinou K, Stefanadis C.. 2009. Homocysteine and coronary atherosclerosis: from folate fortification to therecent clinical trials. Eur Heart J 30(1):6-15. Ganji SH, Kamanna VS, Kashyap ML. 2014. Niacin decreases leukocyte myeloperoxidase: mechanistic role of redox agents and Src/p38MAP kinase. Atherosclerosis 235(2):554-61. Gu-Cheng X, Yu Y, Wang C. 2013. Surgical treatment for diffuse coronary artery diseases. INTECH open access publisher. Guthikonda S, Haynes WG. 2006. Homocysteine: role and implications in atherosclerosis. Curr Atheroscler Rep 8(2):100-6. Harvard School of Public Health. Three of the B Vitamins: Folate, Vitamin B6, and Vitamin B12. Retrieved from http://www.hsph.harvard.edu/nutritionsource/vitamin-b/#introduction. Heart & Stroke Foundation. 2008. Stroke. http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3483991/k.34A8/Statistics.htm#stroke. Lukasova M, Hanson J, Tunaru S, Offermanns S. 20111. Nicotinic acid (niacin): new lipid-independent mechanisms of action and therapeutic potentials. Trends Pharmacol Sci 31(12):700-7. Marsche G, Hammer A, Oskolkova O, Kozarsky K, Sattler W, Malle E. 2002. Hypochlorite-modified High Density Lipoprotein, a High Affinity Ligand to Scavenger Receptor Class B, Type I, Impairs High Density Lipoprotein-dependent Selective Lipid Uptake and Reverse Cholesterol Transport. J Biol Chem 277(35):32172-9. Sahebkar A, Chew GT, Watts GF. 2014. Recent advances in pharmacotherapy for hypertriglyceridemia. Prog Lipid Res 56C:47-66. Sauve AA. 2014. NAD+ and vitamin B3: from metabolism to therapies. J Pharmacol Exp Ther 324(3):883-93. Si Y, Zhang Y, Zhao J, Guo S, Zhai L, Yao S et al. 2014. Niacin inhibits vascular inflammation via downregulating nuclear transcription factor-κB signaling pathway. Mediators Inflamm 2014:263786.

  22. References Tiwari V and Khokhar M. 2014. Mechanism of action of anti-hypercholesterolemia drugs and their resistance. Eur J Pharmacol 741C:156-170. [1] Avocado. Image retrieved from http://www.bjjscandinavia.com/2013/01/19/10-health-benefits-of-avocados/. [2] Free range veal. Image retrieved from http://bffbeef.com/products-2/bff-free-range-veal/. [3] Dates. Image retrieved from http://www.popsugar.com.au/fitness/photo-gallery/35024842/image/35024891/Dates. [4] Sashimi combo. Image retrieved from http://www.sushikiku.com/location1takeout/sashimicombo/. [5] Shiitake mushrooms. Image retrieved from http://drleonardcoldwell.com/2014/04/15/shiitake-mushrooms-can-help-prevent-cervical-cancer-study-finds/.

  23. Summary B vitamins • Essential class: obtained from high-protein foods or supplements • Functions: energy metabolism, RBC production Niacin  nicotinamide  NAD+ and NADP+ • Redox functions: fatty acid/cholesterol synthesis; H carriers; metabolism • Non-redox functions: cell signalling (G-proteins) • Other: alter P450 activity • Antihyperlipidemic effects • Too much LDL leads to atherosclerosis and cardiovascular diseases • Niacin slows and potentially reverses the progression of atherosclerosis • Inhibits hydrolysis of triglycerides into free fatty acids (GPCR109A, in adipocytes) • Inhibits de novo synthesis of triglycerides (DGAT2, in hepatocytes) • Increases functional HDL: improves cholesterol clearance • Reduces activity of MPO, which reduces HOCl- production  less HDL degradation • Anti-atherothrombotic effects • Decrease systemic inflammation • Stabilize plaques • Deficiency causes pellagra (4 “Ds”: dermatitis, diarrhea, dementia, death) • Treat with high dose of nicotinamide

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