1. Thiamin (Vitamin B1): Beriberi Sara Parnell

2. Thiamin Discovered to be an important nutrient during the 1800s when rice was being made with only the endosperm people developed neurological problems (beriberi) Water-soluble B vitamin Structure consists of pyramidine ring and thiazole linked by a methylene bridge Source: http://www.natuurlijkerwijs.com/english/vitamins.htm

3. Food Sources RDA ◦ Men: 1.2 mg ◦ Women: 1.1 mg (up to 1.5 mg if pregnant/lactating) Meat (pork, beef, liver) Salmon Legumes Whole, fortified, or enriched grains In the American diet, majority comes from foods enriched with the vitamin.

4. Biochemistry Thiamin is precursor to the coenzyme thiamin pyrophosphate (TPP) Involved in carbohydrate metabolism  catalyzes synthesis or cleavage of bonds between carbonyl carbons Pyruvate Dehydrogenase Complex Citric Acid Cycle Pentose Phosphate Pathway Source: http://www.chegg.com/homework-help/questions-and-answers/preeti-dhardepartment- chemistrysuny-new-paltz-people-malaysia-belong-communities-local-peo-q4080231

5. Metabolic Pathways PDC Oxidative decarboxylation of pyruvate (via pyruvate dehydrogenase, E1) to form acetyl CoA Thiamin used as building block for TPP The reaction also helps generate ATP Citric Acid Cycle Decarboxylation of α-ketoglutarate Reaction 4 Pentose Phosphate Pathway TPP coenzyme for transketolase, which is needed for NADPH synthesis and pentoses

6. Thiamin Inhibition If oxidative decarboxylation inhibited, ATP cannot be synthesized and acetyl CoA cannot be formed. If acetyl CoA does not form, leads to accumulation of pyruvate, lactic acid, and α- ketoglutarate. Source: http://www.stories-for- children.ca/beriberi-good-discovery.phphttp://www.stories-for- children.ca/beriberi-good-discovery.php

7. Digestion & Absorption Intestinal phosphatases responsible for digestion Mediated by thiamin transporters (ThTr1 and ThTr2 in kidney and intestine) Defects in the gene SLC19A2 (codes for ThTr1) shown to cause deficiency Source: http://www.mikeblaber.org/oldwine/BCH4053/Lecture33/Lecture33.htm

8. Antithiamin Factors Factors that contribute to decreased thiamin absorption Polyhydroxyphenols in coffee, tea, blueberries, and brussel sprouts - inactivate thiamin by oxyreductive process that destroys the thiazole ring Thiaminases in fish – catalyze cleavage of thiamin and decreases uptake of thiamin.

9. Beriberi Beriberi – “beri” means weakness in Singhalese Prevalence is high in Eastern Asian countries Incidence rate unknown Individuals with this disease have high levels of pyruvate and α-ketoglutarate in the blood Can be life threatening, but effects are reversible – mortality is rare Dry beriberi Wet beriberi

10. Dry Beriberi Chronic low thiamin intake Affects nervous system More prominent in adults Muscle weakness Difficulty walking Mental confusion/speech difficulties Strange eye movements Vomiting Acute beriberi : occurs predominantly in infants Lactic acidosis

11. Wet Beriberi Wet beriberi affects the cardiovascular system Cardiomegaly Tachycardia Shortness of breath Peripheral edema

12. Beriberi Alcoholism in developed countries leads to Wernicke’s encephalopathy Biggest cause of thiamin deficiency in the United States Decreased thiamin absorption Alcohol dependency leads to decreased food consumption, but also increased thiamin needs due to liver damage GI cancers, liver disease, IBD can decrease ability to absorb thiamin

13. New Research and Treatments Thiamin deficiency may occur following bariatric surgery Decreased food intake in weeks following surgery Thiamin half life = 20 days Treatment requires 15 to 250 mg daily thiamin supplement for one month or more depending on the severity Thiamin injections can also be given With treatment, symptoms are reversible

14. References (2012). Beriberi: Thiamine deficiency; vitamin b1 deficiency. PubMed Health, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001379/ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001379/ Boyer, R. (2006). Biochemistry. (3rd ed.). Hoboken, NJ: John Wiley & Sons, Inc. Gropper, S., & Smith, J. (2013). Advanced nutrition and human metabolism. (6th ed.). Wadsworth Cengage Learning. Jurgenson, C. T., Begley, T. P., & Ealick, S. E. (2009). The strctural and biochemical foundations of thiamin biosynthesis. Annu. Rev. Biochem., Rabinowitz, S. (2012, April 16). Pediatric beriberi. Retrieved from http://emedicine.medscape.com/article/984721-overview