Download Thiamin (Vitamin B1): Beriberi

Thiamin (Vitamin B1):
Beriberi
Sara Parnell
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
Food Sources
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RDA
◦ Men: 1.2 mg
◦ Women: 1.1 mg (up to 1.5 mg if pregnant/lactating)
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Meat (pork, beef, liver)
Salmon
Legumes
Whole, fortified, or enriched grains
In the American diet, majority comes from foods
enriched with the vitamin.
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-dhardepartmentchemistrysuny-new-paltz-people-malaysia-belong-communities-local-peo-q4080231
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
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 αketoglutarate.
Source: http://www.stories-forchildren.ca/beriberi-good-discovery.php
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
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.
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
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
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Lactic acidosis
Wet Beriberi
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Wet beriberi affects the cardiovascular system
Cardiomegaly
Tachycardia
Shortness of breath
Peripheral edema
Beriberi
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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
New Research and Treatments
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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
References
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(2012). Beriberi: Thiamine deficiency; vitamin b1 deficiency. PubMed Health,
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001379/
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Boyer, R. (2006). Biochemistry. (3rd ed.). Hoboken, NJ: John Wiley & Sons, Inc.
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Gropper, S., & Smith, J. (2013). Advanced nutrition and human metabolism. (6th ed.). Wadsworth
Cengage Learning.
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Jurgenson, C. T., Begley, T. P., & Ealick, S. E. (2009).The strctural and biochemical foundations of
thiamin biosynthesis. Annu. Rev. Biochem.,
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Rabinowitz, S. (2012, April 16). Pediatric beriberi. Retrieved from
http://emedicine.medscape.com/article/984721-overview