Kolluru Viswanatha Chaitanya et al. / Journal of Pharmacy Research 2012,5(11),5144-5148 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info Role of Thiamine in Human Metabolism – A Review

Kolluru Viswanatha Chaitanya*, Venkata Ramana Gopavajhula and Shaik Khasim Beebi Department of Biotechnology, GITAM Institute of Technology, GITAM University, Visakhapatnam-530045, India. Received on:11-07-2012; Revised on: 19-08-2012; Accepted on:23-09-2012

ABSTRACT Thiamine is an important water soluble vitamin essential for humans and obtained from plant and microbial products. This vitamin plays a major role in a number of metabolic reactions occurring in the human body mainly in the protein and carbohydrate metabolisms which are essential for the generation of energy, for RBC synthesis, in the functioning of nervous system, heart and muscles. Severe deficiency of thiamine results in Beri beri, optic neuropathy, Wernicke-Korsakoff syndrome and gastro intestinal disorders. The present review emphasizes on the role of thiamine in human metabolism and the diseases caused due to its deficiency.

Key words: Thiamine, Human metabolism, Beri Beri. INTRODUCTION Thiamine is one of the eight water soluble B complex vitamins, named as phosphate throwing light on complexity of thiamine metabolism[9]. Till vitamin B1 and is one of the first organic compounds, identified and date, no known physiological activity of thiamine mono phosphate has characterized in 1930’s. It is also termed as Aneurin as its deficiency resulted been determined. in several neurological disorders. Thiamine is synthesized by bacteria, fungi and plants. Animals lack privilege of its bio synthesis hence obtained in Phosphate derivative of thiamine was characterized as thiamine pyro optimum amounts from diet as an essential nutrient[1]. Several compounds phosphate (TPP), which is active in multiple cellular processes. TPP serves such as allithiamine, prosultiamine, furultiamine, benfotiamine etc. were as a co enzyme and also as a transient carrier of specific atoms or functional discovered as derivatives of thiamine, which alleviate the symptoms of its groups and is pivotal in catabolism of sugars and amino acids. Its presence deficiency[2]. in pyruvate dehydrogenase, 2-oxogluterate dehydrogenase (a-ketogluterate dehydrogenase), branched chain a keto acid dehydrogenase, 2-hydroxy Thiamine along with other vitamins of the B complex, assists and regulates phytanoyl-CoA lyase and transketolase in various metabolic pathways of carbohydrate, fat and protein metabolism which are essential mechanisms several species is noteworthy. It is present in Pyruvate decarboxylase of for the production of energy in humans[3]. Thiamine also contributes for several bacteria and yeasts[10]. The enzymes transketolase, pyruvate hemoglobin synthesis and RBC production. It is essential for the synthesis dehydrogenase (PDH), and 2-oxoglutarate dehydrogenase (OGDH) play a of acetylcholine thereby functioning of nervous system and also for the pivotal role in carbohydrate metabolism. Similarly transketolase is crucial functioning of heart and muscles, and is a key metabolite in the biosynthesis in the pentose phosphate pathway which is a major pathway for the of g-amino butyric acid (GABA)[4]. Unattended or untreated thiamine fabrication of the pentose sugars, deoxy ribose and ribose[11]. Both PDH deficiency will pose a potential threat or fatal blow on health[5]. Deficiency and OGDH are equally important in generation of ATP, an in famous energy of thiamine leads to many syndromes and diseases such as Korsacoffs form in the power house of the cell. PDH concatenates glycolysis to the syndrome, optic neuro pathy and Beri beri etc[6]. In birds, its deficiency citric acid cycle where OGDH catalyzes a rate limiting step in the citric acid causes Poly neuritis[7]. Still exact mechanisms of thiamine deficiency leading cycle. In nervous system, PDH involvement is necessary for the production to specific symptoms need to be investigated. of acetylcholine[12]. The list of metabolic pathways along with thiamine derived enzymes was given in Table 1. Physical and Chemical Properties of Thiamine Thiamine contains an amino pyrimidine ring and a thiazole ring along with Table 1: List of enzymes utilizing thiamin pyrophosphate and their pathways the methyl hydroxyl ethyl side chains linked by a methylene bridge in its Enzyme Pathways structure. Thiamine is soluble in water, methanol, glycerol and is more stable at acidic pH and unstable in solutions of alkaline nature[8]. This Pyruvate decarboxylase Ethanol fermentation vitamin is highly sensitive to heat, U.V light and gamma irradiation. The Pyruvate dehydrogenase Synthesis of acetyl-CoA Transketolase Carbon-assimilation reactions sensitivity decreases with decreasing temperature. Pentose phosphate pathway a-Ketoglutarate dehydrogenase Citric acid cycle Derivatives and Functions of Thiamine Thiamine is active at its phosphorylated forms which occur as thiamine The existence of thiamine triphosphate (ThTP) which is the neuro active mono phosphate, thiamine tri phosphate and thiamine di phosphate. form of aneurin was observed recently in bacteria, fungi, plants and animals [13] Recently a new form of thiamine phosphate has been identified, which is giving a hint of its mundane role at cellular level . During amino acid [14] named as Adenosine thiamine tri phosphate and Adenosine thiamine di starvation the response of E.coli substantiates the above point . In E.coli, during carbon starvation, adenosine thiamine triphosphate (AThTP) is found *Corresponding author. to be accumulated which may account for 20 % of the total vitamin B1 Dr. K.V.Chaitanya present in the organism. In minute forms it occurs in the yeast, roots of Assistant Professor higher plants and animal tissue. Adenosine thiamine diphosphate (AThDP) Department of Biotechnology, GIT is present in the minute amounts in vertebrate liver[15]. GITAM University Visakhaptnam- 530045, A.P. India.

Journal of Pharmacy Research Vol.5 Issue 11.November 2012 5144-5148 Kolluru Viswanatha Chaitanya et al. / Journal of Pharmacy Research 2012,5(11),5144-5148 Nutrition in Dietary Supplements place through simple passive diffusion [17]. In the jenunal cells, the transport Thiamine is not a nutrient found in plethora of dietary supplements unlikely, is at its maximum due to presence of thiamine pyrophospo kinase. Release in low concentrations, in a wide variety of edibles. Its concentration is at of thiamine by the serosal cells of intestine is found to be dependent on Na+ zenith in yeast, yeast extract and also in the pork. By virtue of ubiquity dependent ATPase. Most of the thiamine content in the blood is bound to cereal grains became one of the most vital resources of thiamine. However, serum proteins and in the erythrocytes. The transport of thiamine in during the refining process, outer layers of grains were peeled away which erythrocytes is Na+ independent, electroneutral process exhibiting saturable posses most of the thiamine. Thus whole grain is preferable rather than a and non-saturable components. The process is carrier mediated and follows refined one. As an exemplary we consider that 100mg of white flour consists Michelis-Menten kinetics. In the rat serum, a binding protein namely of only 0.06 mg of thiamine whereas the same amount of whole wheat flour thiamine-binding protein has been identified, which is assumed to be a consists of 0.55 mg of thiamine. Oat meal, flax, sun flower seeds, brown carrier protein regulated by hormones intended for tissue distribution of rice, whole grain rye, asparagus, kale, cauliflower, potatoes, oranges, eggs, thiamine[9]. liver of the beef, pork and chicken are rich sources of thiamine[6]. Betaxin which is also known to be thiamine hydrochloride, is a hygroscopic Uptake and distribution of thiamine crystalline white color food additive used in gravies or soups to give meaty Low concentrations of thiamine are facilitated by transepethelial or brothy flavor. Betaxin evolves as an intermediate from the thiamine-Hcl transport[18]. Thiamine uptake by the cells of tissues and blood is facilitated reaction after hydrolysis and phosphorylation, which is used in the form of by active and passive diffusions. Brain is in constant demand of huge TPP in many enzymatic, carbohydrate, amino and fatty acid reactions. To amounts of thiamine but may not get enough due to blood brain barrier and prevent thiamine deficiency a varied diet is essential. Average dietary passive distribution. Almost 80 % of the total intracellular thiamine is thiamine in take among young adult men and women is in the ratio of 2mg/ phosphorylated where ions bounds to proteins. Soluble thiamine transporter day: 1.2 mg/day respectively (Table 2). However a survey on sexagenarians is substantiated by Na+ and a transcellular proton gradient is found to be and above resulted in thiamine intake of 1.4 mg/day in men and 1.1 mg/day mediating thiamine secretions and uptake in some tissues[6]. in women. Adding fuel to the fire both poverty and institutionalization increased the inadequate amounts of thiamine among the old population16 Optimum concentration of thiamine is stored temporarily in brain, heart, (Table 3). skeletal muscles kidneys and liver accounting to almost 25 to 30 mg. Thiamine Table 2: Recommended dietary allowance of thiamine monophsophate is present in cerebrospinal fluid, milk, plasma and also presumed to be found in all extracellular fluids. Free thiamine and highly Life stage Age Male (mg/day) Female (mg/day) phosphorylated forms of thiamine such as ThMP, ThPP,ThTP etc. can cross the cell membranes although thiamine content is found to be less in Infants 0-6 months 0.2 0.2 human beings in contrast to remaining species[9]. Acid metabolites such as Infants 7-12 months 0.3 0.3 Children 1-3 years 0.5 0.5 thiamine acetic acid, 2-methyl 4-amino 5-pyrimidine carboxylic acid and 4- Children 4-8 years 0.6 0.6 methyl thiazole 5-acetic acid along with thiamine are principally excreted Children 9-13 0.9 0.9 via urine[19]. Adolescents 14-18 years 1.2 1.0 Adults 19 years & older 1.2 1.1 Thiamine Deficiency Pregnancy all ages – 1.4 Breast feeding all ages – 1.4 Reasons for thiamine deficiency Table 3: Dietary food composition of thiamine Aqueous Thiamine fluid is dispersed throughout the body. It is not stored Food product ( 100 g) Levels of Thiamine (mg) in the body and appreciable amount of thiamine is replenished everyday as it lasts in the body only for 14-18 hours after consumption or ingestion. Lentils 0.17 The excessive loss of thiamine from the body, inadequate thiamine intake, Peas 0.21 increased requirement for thiamine and consumption of anti-thiamine factors Long grain Brown rice 0.19 Long grain white rice {enriched} 0.26 in food, or a combination of these factors may result in thiamine deficiency. Long grain white rice {unenriched} 0.04 Whole wheat bread 0.10 When there is inadequacy in consumption of appropriate amount of thiamine White bread {enriched} 0.11 necessary for the body, its deficiency deteriorates the health, which is Fortified Breakfast Cereal 0.5-2.0 prevalent in many under developed countries[20]. In many low-income Wheat germ Breakfast Cereal 4.47 Pork,lean(cooked) 0.72 populations, vitamin B1 deficiency is common due to their imbalanced diet Brazil nuts 0.18 habits with huge amounts of carbohydrates and low amounts of thiamine. Pecans 0.19 Polishing the food grains is adding more complexity to the problem. Infants Spinach 0.09 are vulnerable to infantile Beri beri due to the milk they take from their Orange 0.10 mothers which lacks thiamine. This in turn indicate that even the women at Cantaloupe 0.11 Milk 0.10 the stage of post pregnancy need to have adequate thiamine in order to Egg (cooked) 0.03 avoid ill effects of its deficiency. Even developed countries are not exceptional in this case where addiction to alcohol is associated with low thiamine Cellular absorption and transport of thiamine intake in diet resulting in deficiency problems.

Absorption When there is more demand for thiamine, one can observe symptoms such Substantiated by the action of pyro phosphate and pentose phosphate, as fever, strenuous physical exertion, and adolescent growth etc; Post thiamine is released in the distal part of the small intestine and its absorption pregnancy nutritional requirements and breast-feeding to infants will increase takes place at the proximal part with the rate decreasing in stomach and its demand. It is found from the investigations that the malaria patients in colon. The concentrations above 2.5mg of thiamine are largely unabsorbed. Thailand facing sever thiamine deficiency more frequently than normal The process of thiamine absorption in the intestine occurs mainly through individuals[21]. Malarial infection increases the metabolic demand for the two different mechanisms. At lower concentrations (>1mmol), thiamine is glucose in the body. Due to thiamine deficiency, enzymes which are active absorbed by active carrier mediated system involving intracellular in glucose metabolism gets inactivated inhibiting the synthesis of glucose phosphorylation. The phosphorylation takes place both in averted jejuna adding up to the demand. In predisposed individuals, this stress may sacs and enterocytes. Phosphorylation of thiamine forms an effective means exacerbate thiamine deficiency. Thiamine deficiency is also found to be of membrane transport. At higher concentrations, the absorption takes Journal of Pharmacy Research Vol.5 Issue 11.November 2012 5144-5148 Kolluru Viswanatha Chaitanya et al. / Journal of Pharmacy Research 2012,5(11),5144-5148

G

Fig. 1: Effects of thiamine on human health increased in HIV infected individuals, which may be due to lack of thiamine Thiamine is a co-factor for several key enzymes involved in energy intake as per the requirement[22]. Due to severe alcoholism, the efficacy of metabolism. Metabolic disturbances caused by thiamine deficiency can intestinal absorption is impaired which results in additional requirement of stimulate the nerve cell damage through several mechanisms including the thiamine. Diuretics may prevent reabsorption of thiamine by the kidneys impairment in carbohydrate metabolism leading to energy failure and resulting in enhanced urinary flow leading to over excretion followed by accumulation of free radicals[28], stress on endoplasmic reticulum and rapid thiamine deficiency[23]. Patients with kidney failure who are undergoing decrease in the K+ membrane conductance[29]. All these mechanisms can hemodialysis are subjected to thiamine deficiency due to loss in huge aggravate neuron damage leading to neurodegenerative disorders such as amounts[24]. Alcohol addiction coupled with high fluid intake along with Wernicke-Korsakoff syndrome[30]. Chronic diseases like gastro intestinal excessive urine outflow may experience increased loss of thiamine[25]. diseases and persistent vomiting associated with impaired nutritional status will exacerbate thiamine deficiency[31]. Deficiency of thiamine might be Anti-thiamine factors & antagonists high in the diabetes patients due to the plethora of complications[32]. Beri Thiamine levels in the body can be down-regulated by a specific group of beri, optic neuropathy, Wernicke-Korsakoff syndrome etc. were well known compounds and enzymes called anti thiamine factors and antagonists, which diseases caused due to vitamin B1 deficiency[33]( Fig.1). occur naturally in food and contribute to the destruction of thiamine levels when consumed. These anti thiamine factors are also present in certain Beriberi plants seldom reacting with thiamine to form an inactive oxidized product. Beri beri also called as clinically apparent thiamine deficiency is a disease Thiaminases are the enzymes that are found in ferns like Pteridum aquilinum, associated with a variety of syndromes such as peripheral neuropathy, Equisetum arvense, Marsilea drummondii and Cheilanthes sieberi, in the myocardial dysfunction, encephalopathy, hypoglycemia and lactic acidosis. viscera of raw and shell fishes and even in few bacteria like Clostrridium Beriberi became a dominant public health problem in Asia, responsible for sporogenes and Bascillus species, which cleaves the thiamine molecule and a considerable mortality, especially amongst infants with all most three render it biologically inactive. Bacterial thiaminases are cell surface enzymes forms of disorders namely dry, wet and infantile Beriberi[34]. Peripheral that need dissociation from the membrane, to get activated. These neuropathy is one of the foremost important features of dry (nervous or dissociations occur at acidic conditions in ruminants. Rumen bacteria are paralytic) Beri beri. Peripheral neuropathy is associated with a sub acute capable of reducing the sulfate to sulfite which builds up negative effects motor axonal neuropathy, which mimic Guillain Barre syndrome in thiamine under high dietary intake of sulfate causing thiamine antagonistic activity. deficiency or as large fibre proprioceptive central peripheral axonal There are two types of thiaminases, Type I: found in shell fish, ferns and neuropathy represented as a sub acute sensory ataxia[32]. Burning feet some bacteria. It displaces the pyrimidine methylene group of thiamine syndrome may occur in the initial days of this sort of deficiency. Several with a nitrogenous base or SH-compound to eliminate the thiazole ring. other symptoms like muscular pain with tenderness adding difficulty in Type II: Reported in bacteria, acts through the hydrolytic cleavage of the rising from a squatting position, abnormal exaggeration of reflexes with a methylene-thiazole-N bond to yield pyrimidine and thiamine moieties. Both diminished sensation coupled by weakness in legs. Patients may also the types of enzymes require a co-substrate for the action which is either an experience seizures[35]. Wet beri beri is characterized by cardio vascular amine or proline and sometimes cysteine. Once the thiamine molecule is manifestation along with the neurological symptoms, showing rapid heart cleaved by a specific thiaminase, it makes the body incapable of restoring it, rate enlargement, severe swelling and difficulty in breathing, sometimes there by inducing thiamine deficiency inspite of sufficient amount of thiamine may leads to cognitive heart failure. It was also associated with the in the diet[26]. Thiamine levels in the human body are also affected by certain symptoms such as peripheral neuropathy, mental confusion, edema, heat stable antagonists like polyphenols (e.g. caffeic acid, chlorogenic acid, muscular atrophy, tachycardia and cardiomegaly[36]. Infantile thiamine is tannic acid), flavonoids (e.g. quercetin, rutin) and haemin. Interaction between another manifestation of thiamine, posing threat to the infants life through thiamine and these compounds results in the oxidation of thiazole ring cardiac, pseudo meningitic or aphonic forms of disorders[37]. making it incapable to absorb[27]. Cerebral Beriberi is a chronic situation caused either due to alcohol abuse or Diseases resulting in the thiamine deficiency malnutrition or genetic manipulations leading to Wernicker’s encephalopathy Journal of Pharmacy Research Vol.5 Issue 11.November 2012 5144-5148 Kolluru Viswanatha Chaitanya et al. / Journal of Pharmacy Research 2012,5(11),5144-5148 and Korsakoff’s psychosis. Wernickers encephalopathy is a disorder due disease was caused due to the abnormality in the activation of pyruvate to insufficient levels of thiamine in the brain, showing the symptoms like dehydrogenase complex, an important process in thiamine metabolism. Sub abnormal eye movements, abnormalities in mental function that may include acute necrotizing encephalomyelopathy, opaclonic cerebellopathy which a confused apathetic state or a profound memory disorder termed is a paraneoplastic syndrome and Nigerian ataxia are the disorders implicated Korsakoff’s amnesia or Korsakoff’s psychosis, stance and gait abnormalities. due to putative role of the thiamine. It is found that inherited disorders of Korsakoff’s involves neuronal loss, that is, damage to neurons, gliosis, ThDP dependent enzymes are responding when they are treated with [46] which is a result of damage to supporting cells of the central nervous thiamine . system and hemorrhage or bleeding in mammillary bodies[38]. When Wernicke’s encephalopathy accompanies Korsakoff’s syndrome, the Drug-drug interactions in relation to thiamine levels in human body combination is called the Wernicke-Korsakoff syndrome[39]. Drugs, which are administered into the human body for different disease, also regulate the levels of thiamine. Individuals suffering from epilepsy taking anticonvulsant phenytoin for longer periods of time have been Optic neuropathy reportedly found to be with reduced thiamine levels in blood. Drugs used in There is probability of damaging the optical nerve due to vitamin B1 the cancer therapy such as flurouracil will impede the process of deficiency which is characterized by cecocentral scotomas, impaired color phosphorylation between thiamine-to-thiamine pyrophosphate, which perception and bilateral visual loss. It was learned from the ophthalmological inhibits its production[47]. Dieuritics such as flurosemide also known as findings that optic disk in acute phase shows a bilateral oedema post ceded Lasix may increase the urinary excretion of thiamine in individuals of marginal by bilateral optic atrophy[32]. thiamine intake, which accelerate deficiency[48]. Extreme alcoholism also increases the excretion of thiamine due to impaired gut function to absorb Congestive heart failure thiamine[49]. Wet beriberi occurs due to severe thiamine deficiency and can lead to congestive heart failure as a result of impaired cardiac function. Congestive CONCLUSIONS AND FUTURE PROSPECTS heart failure is common in the people of old age albeit, such manifestations Thiamine is an essential micronutrient, which plays a pivotal role in controlling of beriberi are rare in several industrialized countries. When measured with the health of humans. Its presence is very important for the function of vital the transketolase assay, it was found that thiamine nutritional status among organs in the human body and also in the key metabolic pathways like patients of congestive heart failure and myocardiac diseases is fairly low carbohydrate metabolism for the energy release. Even though there is no due to the administration of diuretics as a part of treatment to congestive upper limit to the thiamine intake, presence of anti thiamine factors naturally heart failure which potentially excretes thiamine leading initially to marginal suggest that there is an in built mechanism in metabolic pathways to regulate thiamine deficiency. Risk of thiamine deficiency is high in aged rather than the levels of thiamine, which need to be elucidated clearly. Its role in human in young[36]. health after deterioration also need to be understood well with ample amount of sample size to direct necessary experiments with acquainted randomization Cancer to enlighten more about this essential vitamin. It has been observed that rapid growth of tumors in some patients, when they are suffering with cancer coupled with thiamine deficiency. It is found REFERENCES from the studies that the thiamine is a requirement for the cancer cells, 1. Webb ME, Marquet A, Mendel RR, Rebeille F, Smith AG. which divide rapidly[40]. Rapidly dividing cells will have a great demand for Elucidating biosynthetic pathways for vitamins and cofactors. nucleic acids but some cancerous cells substantiate more on the TPP- Nat Prod Rep 2007; 24: 988–1008. dependent enzymes like transketolase to vouch safe ribose-5-phosphate 2. Gangolf M, Czerniecki J, Radermecker M, Detry O, Nisolle M. which is mandatory for the synthesis of nucleic acid. It is in common Thiamine status in humans and content of phosphorylated practice to give thiamine supplements to the cancer patients whether they thiamine derivatives in biopsies and cultured cells. Plos One 2010; are found to be deficient in vitamin B1 or not. However, it was reported 5: e13616. that thiamine ingestion in overdoses may act as fuel for the growth of 3. Thomson AD, Jane Marshall E. The natural history and malignant tumors which in turn accelerate the rate of cancer development[41]. pathophysiology of Wernicke's encephalopathy and Korsakoff's psychosis. Alcohol and Alcoholism 2006; 41: 151-158. Alzheimer’s disease 4. Krishnaswamy B, Hamid MS. Functional role of specific amino Alzheimer’s disease is one of the most common forms of dementia associated acid residues in human thiamine transporter SLC19A2: mutational with neuro degeneration. Thiamine levels were reported to be reduced in the analysis. Am J Physiol Gastrointest Liver Physiol 2002; 283: patients suffering with the Alzheimer’s disease but improved after the oral G37-G43. supplementation of thiamine[42]. Patients suffering with Alzheimer’s disease 5. Sneha C, Narayan Agarwal, Ramya B, Ramana GV, Chaitanya have decreased the function of thiamine dependent enzymes thiamine KV.Characterization of hydroxymethyl pyrimidine diphosphate and thiamine diphosphatase activities. It was also reported monophosphate kinase for thiamine synthesis in wheat. Journal that lack of thiamine can cause dementia in people suffering with Wernicke- of Advanced Bioinformatics Applications and Research 2011; 2: Korsakoff syndrome[43]. 167-172. 6. Combs G, Jr F. The vitamins: fundamental aspects in nutrition Genetic disorders and thiamine deficiency and health 3rd edition. Ithaca, NY: Elsevier Academic Press 2008. Even though the genetic diseases caused by the thiamine transport are rare, 7. Koikea H, Misua K, Hattoria N, Itoa S, Ichimuraa M, Itoa H, their outcome is serious and at time fatal. Mutation in high affinity thiamine Hirayamaa M, Nagamatsua M, Sasakib I, Sobuea G. transporter genes such as SLC19A2 results in Thiamine Responsive Postgastrectomy polyneuropathy with thiamine deficiency. J Megaloblastic Anemia (TRMA), a rare autosomal disorder with sensorineural Neurol Neurosurg Psychiatry 2001; 71:357-362. deafness and diabetes mellitus, as symptoms[44]. When thiamine deficiency 8. Mahan LK, Escott-Stump S. Krause's food, nutrition, & diet symptoms are absent in the patients of TRMA, then it was suggested therapy 10th edition. Philadelphia: W.B. Saunders Company 2000. super fluousness of thiamine transport system, which leads to the discovery 9. Bettendorff L, Wirtzfeld B, Makarchikov AF, Mazzucchelli G, of SLC19A3 a second high affinity thiamine transporter acting as a Frédérich M, Gigliobianco T, Gangolf M, De Pauw E, Angenot L contingency[45]. Sub acute necrotizing encephalomyelopathy or Leigh disease and Wins P. Discovery of a natural thiamine adenine nucleotide. is an inherited disorder effecting the central nervous system among infants Nature Chem Biol 2007; 3: 211–212. during their first five years of life span. It was hypothesized that Leigh 10. Tadhg PB, McMurry J. The organic chemistry of biological

Journal of Pharmacy Research Vol.5 Issue 11.November 2012 5144-5148 Kolluru Viswanatha Chaitanya et al. / Journal of Pharmacy Research 2012,5(11),5144-5148 pathways. Roberts and Co. Publishers 2005. induces endoplasmic reticulum stress in neurons. Neuroscience 11. Wikner C, Nilsson U, Meshalkina L, Udekwu C, Lindqvist Y, 2007; 144: 1045-1056. Schneider G. Identification of catalytically important residues in 30. Lonsdale D. A review of the biochemistry, metabolism and clinical yeast transketolase. Biochemistry 1997; 36: 15643–15649. benefits of thiamine(e) and its derivatives. Evid Based 12. Ronowska A, Dys A, Jankowska-Kulawy A, Klimaszewska-Lata Complement Alternat Med 2006; 3: 49-59. J, Bielarczyk H, Romianowski P, Pawelczyk T, Szutowicz A. 31. Bettendorff L, Wins P. Thiamine diphosphate in biological Short-term effects of zinc on acetylcholine metabolism and chemistry: New aspects of thiamine metabolism, especially viability of SN56 cholinergic neuroblastoma cells. Neurochem Int triphosphate derivatives acting other than as cofactors. FEBS J 2010; 56:143-151. 2009; 276: 2917–2925. 13. Makarchikov AF, Lakaye B, Gulyai IE, Czerniecki J, Coumans 32. Spinazzi M, Angelini C, Patrini C. Subacute sensory ataxia and B, Wins P, Grisar T, Bettendorff L. Thiamine triphosphate and optic neuropathy with thiamine deficiency. Nat Rev Neurol 2010; thiamine triphosphatase activities: from bacteria to mammals. 6:288-293. Cell Mol Life Sci 2003; 60: 1477–1488. 33. Kopelman MD, Thomson AD, Guerrini I, Marshall EJ The 14. Lakaye B, Wirtzfeld B, Wins P, Grisar T, Bettendorff L. Thiamine Korsakoff syndrome: clinical aspects, psychology and treatment. triphosphate, a new signal required for optimal growth of Alcohol Alcohol 2009; 44:148–154. Escherichia coli during amino acid starvation. J Biol Chem 2004; 34. Khounnorath S, Chamberlain K, Taylor AM, Soukaloun D, 279: 17142–17147. Mayxay M. Clinically unapparent infantile thiamine deficiency 15. Frédérich M, Delvaux D, Gigliobianco T, Gangolf M, Dive G, in vientiane, Laos. PLoS Negl Trop Dis 2011; 5: e969. Mazzucchelli G, Elias B, De Pauw E, Angenot L, Wins P, 35. Thurnham D Beriberi. Encyclopedia of Human Nutrition, 2nd Bettendorff L. Thiamineylated adenine nucleotides-chemical edition. London: Academic Press 2005. synthesis, structural characterization and natural occurrence. FEBS 36. Essa E, Michael RV, Sakima S, Shivraman G, Subha VR, Richard Journal 2009; 276: 3256–3268. JG. Cardiovascular magnetic resonance in wet beriberi. Journal of 16. Russell RM, Suter PM. Vitamin requirements of elderly people: Cardiovascular Magnetic Resonance 2011; 13:41-43. an update. Am J Clin Nutr 1993; 58: 4-14. 37. Soukaloun D, Lee SJ, Chamberlain K, Taylor AM, Mayxay M. 17. Rindi G, Laforenza U. Thiamine intestinal transport and related Erythrocyte transketolase activity, Markers of cardiac issues: recent aspects. Proc Soc Exp Biol Med 2000; 224:246- dysfunction and the diagnosis of infantile Beriberi. PLoS Negl 255. Trop Dis 2011; 5: e971. 18. Tanphaichitr V. Thiamine. Modern nutrition in health and disease. 38. Oudman E. Intact memory for implicit contextual information in 9th edition. Baltimore: Lippincott Williams & Wilkins 1999. Korsakoff's amnesia. Neuropsychologia 2011; 49: 2848–2855. 19. Rindi G. Thiamine. Present Knowledge in Nutrition. 7th edition. 39. Kessels RPC, Van Oort R. Executive dysfunction in Korsakoff’s Washington D.C. ILSI Press 1996. syndrome: time to revise the DSM criteria for alcohol-induced 20. Krishna S, Taylor AM, Supanaranond W. Thiamine deficiency persisting amnestic disorder?. International Journal of Psychiatry and malaria in adults from southeast Asia. Lancet 1999; 353: 546- in Clinical Practice 2009; 13: 78–81. 549. 40. Lee BY, Yanamandra K, Bocchini JA Jr. Thiamine deficiency: a 21. Muri RM, Von Overbeck J, Furrer J, Ballmer PE. Thiamine possible major cause of some tumors?. Oncol Rep 2005;14:1589- deficiency in HIV-positive patients: evaluation by erythrocyte 1592. transketolase activity and thiamine pyrophosphate effect. Clin 41. Boros LG, Brandes JL, Lee WN. Thiamine supplementation to Nutr 1999;18:375-378. cancer patients: a double edged sword. Anticancer Res 1998; 22. Suter PM, Haller J, Hany A, Vetter W. Diuretic use: a risk for 18:595-602. subclinical thiamine deficiency in elderly patients. J Nutr Health 42. Khanh VQL, Lan THN, Role of Thiamine in Alzheimer's Disease. Aging 2000; 4:69-71. American Journal of Alzheimer's Disease and Other Dementias 23. Hung SC, Hung SH, Tarng DC, Yang WC, Chen TW, Huang TP. 2011; 26: 588-598. Thiamine deficiency and unexplained encephalopathy in 43. Michael G, Robert AH, Marianne FC. Plasma Thiamine Deficiency hemodialysis and peritoneal dialysis patients. Am J Kidney Dis Associated with Alzheimer's Disease but Not Parkinson's Disease. 2001; 38: 941-947. Metabolic Brain Disease 1998; 13: 43-53. 24. Wilcox CS. Do diuretics cause thiamine deficiency?. J Lab Clin 44. Borgna-Pignatti C, Azzalli M, Pedretti S. Thiamine-responsive Med 1999;134: 192-193. megaloblastic anemia syndrome: long term follow-up. J Pediatr 25. Zajicek JL, Brown L, Brown SB, Honeyfield DC, Fitzsimons 2009; 155:295-297. JD, Tillitt DE. Variations of thiaminease I activity pH 45. Zaman T, Kadivar M and Moradian R. Thiamine–responsive dependencies among typical great lakes forage fish and megaloblastic anemia, sensorineural deafness and diabetes mellitus. Paenibacillus thiamineolyticus. J Aquat Anim Health 2009 ; Acta Medica Iranica 2006; 44: 425- 428. 21:207-216. 46. Narasimha Rao. S, Shalini Mani, Karuna Madap, Kranthi Kumar 26. Kruse M, Navarro D, Desjardins P, Butterworth RF Increased M. V, Lalji Singh, and Giriraj Ratan Chandak . High prevalence of brain endothelial nitric oxide synthase expression in thiamine infantile encephalitic Beriberi with overlapping features of Leigh's deficiency: relationship to selective vulnerability. Neurochem Int disease. J Trop Pediatr 2008; 54: 328-332. 2004; 45: 49-56. 47. Schumann K. Interactions between drugs and vitamins at advanced 27. Martin P, Singleton CK, Hiller-Sturmhofel S. The role of thiamine age. Int J Vitam Nutr Res 1999; 69:173-178. deficiency in alcoholic brain disease. Alcohol Res Health 2003; 48. Rieck J, Halkin H, Almog S, et al. Urinary loss of thiamine is 27: 134-142. increased by low doses of furosemide in healthy volunteers. J 28. Oliveira FA, Galan DT, Ribeiro AM, Santos CJ. Thiamine Lab Clin Med 1999; 134: 238-243. deficiency during pregnancy leads to cerebellar neuronal death in 49. Zenuk C, Healey J, Donnelly J, Vaillancourt R, Almalki Y, Smith rat offspring: Role of voltage-dependent K(+) channels. Brain S. Thiamine deficiency in congestive heart failure patients receiving Res 2007; 1134: 79-86. long term furosemide therapy. Can J Clin Pharmacol 2003;10:184- 29. Wang X, Wang B, Fan Z, Shi X, Ke ZJ, Luo J Thiamine deficiency 188. Source of support: Nil, Conflict of interest: None Declared

Journal of Pharmacy Research Vol.5 Issue 11.November 2012 5144-5148