Molecular Mechanisms of Thiamine Utilization.

Abstract

Thiamine is required for all tissues and is found in high concentrations in skeletal muscle, heart, liver, kidneys and brain. A state of severe depletion is seen in patients on a strict thiamine-deficient diet in 18 days, but the most common cause of thiamine deficiency in affluent countries is alcoholism. Thiamine diphosphate is the active form of thiamine, and it serves as a cofactor for several enzymes involved primarily in carbohydrate catabolism. The enzymes are important in the biosynthesis of a number of cell constituents, including neurotransmitters, and for the production of reducing equivalents used in oxidant stress defenses and in biosyntheses and for synthesis of pentoses used as nucleic acid precursors. Because of the latter fact, thiamine utilization is increased in tumor cells. Thiamine uptake by the small intestines and by cells within various organs is mediated by a saturable, high affinity transport system. Alcohol affects thiamine uptake and other aspects of thiamine utilization, and these effects may contribute to the prevalence of thiamine deficiency in alcoholics. The major manifestations of thiamine deficiency in humans involve the cardiovascular (wet beriberi) and nervous (dry beriberi, or neuropathy and/or Wernicke-Korsakoff syndrome) systems. A number of inborn errors of metabolism have been described in which clinical improvements can be documented following administration of pharmacological doses of thiamine, such as thiamine-responsive megaloblastic anemia. Substantial efforts are being made to understand the genetic and biochemical determinants of inter-individual differences in susceptibility to development of thiamine deficiency-related disorders and of the differential vulnerabilities of tissues and cell types to thiamine deficiency.

Vitamin B1 in critically ill patients: needs and challenges

“…Peripheral vasodilation, biventricular myocardial failure, volume overload, tachycardia, depression of left ventricular function with low ejection fraction, sudden onset cardiac failure and acute renal failure are just some of the signs of wet beriberi [6,63,64]. In contrast, signs of dry beriberi include ophthalmoplegia, ataxia, confusion, memory loss and confabulation in chronic settings [6,65,66]. These symptoms seem to be variable depending on age and the spectrum of the deficiency and may only precipitate during periods of increased energy demand or metabolism in individuals with only a subclinical deficiency.…”

“…These stores can however become depleted in as little as 18 days after the cessation of thiamine intake [2,3]. This leads to a variety of clinical features that are often vague and sometimes non-specific [4][5][6]. In recent years, there has been increasing recognition of its importance in neurological function as well as the discovery of new thiamine adenine nucleotide species [6][7][8][9][10].…”

“…This leads to a variety of clinical features that are often vague and sometimes non-specific [4][5][6]. In recent years, there has been increasing recognition of its importance in neurological function as well as the discovery of new thiamine adenine nucleotide species [6][7][8][9][10]. A greater understanding of human thiamine biochemistry is highly desirable and clinically relevant as thiamine deficiency (TD) is still reported worldwide.…”

"Infusão de glicose e tiamina em ratos tratados com dose aguda de etanol"

“…Masalkar e Abhang (2005), utilizando o MDA como índice de peroxidação lipídica em pacientes com doença hepática ocasionada pelo álcool, encontraram uma correlação positiva entre os níveis de MDA e o aumento na severidade da doença.…”

“…Segundo Lieber (2005), o consumo de álcool pode levar a danos no organismo decorrentes de desnutrição primária, ou seja, substituição de outros nutrientes pelo álcool, ou secundária; devido à má digestão e/ou má absorção de nutrientes. Somando-se à desnutrição, o metabolismo do etanol gera substâncias de alta reatividade como o acetaldeído e radicais livres, que provocam injúrias em órgãos inespecíficos, quer por excessivo consumo, quer por modificações em moléculas essenciais à homeostase do organismo.…”