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Can you list 4 enzymes that are thiamine-dependent and the reactions they catalyze? How does thiamine deficiency result in the clinical features of the WK syndrome?

Significance Of Thiamine in Human Metabolism and Medicine
Significance Of Thiamine in Human Metabolism and Medicine
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Thiamin, widely called vitamin B1, is a vital nutrient for all cellular species. Thiamin
comprises a pyrimidine group and thiazole ring, which together form a structure that contains
sulfur with two rings connected by a methylene cluster. Thiamin is required in all mammalian
diets. It contributes to the production of energy from sources containing carbohydrates by acting
as a coenzyme or prosthetic group during the conversion of many carbon chains in the Krebs
cycle and when glucose is converted to ATP.1 Thiamin is a reactant in both the hexose and
pentose monophosphate pathways. Further to it being a key element in metabolic activities,
thiamin is also essential for other activities, like performing oxidative decarboxylation in
proteins, initiating conduction pathways in neuroblastomal cells, and operating as phosphate
ester forms in the intestinal lumen.
Through its control and activating the immune cells and proteins of the immune structure,
thiamin is engaged in some tasks in the immune body system. In this case, thiamin is intimately
associated with hemin-dependent oxygenases, the effect of which it impacts the release of ICAM
(intracellular adhesion molecule) proteins on the immune system.2 In immunological reactions,
ICAMs bind integrins, which then influence T-cell activity and other immune system cells.
Thiamin’s function in developing CD40L-mediated inflammatory and immunological processes
and immunoglobulins in the cells of the brain also contributes significantly to the immune
system’s responsiveness.
Shielding the sulfhydryl groups on the cell surfaces from oxidation provides antioxidative
effects on neutrophil cells and enhances the activity of the cell via its antioxidative function.1
Thiamin also protects macrophages by inhibiting the oxidative stress-induced activation of NFB, that drives macrophages to produce a range of inflammatory indicators, including
chemokines, cytokines, immune-responsive proteins, and growth factors. Thiamin is also an anti-
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inflammatory factor that prevents inflammation from repeating and controls the production of
inflammatory chemicals.1
Thiamin plays a crucial role in several enzymatic activities associated with brain
formation, brain activity, maintenance, and interneuronal communication. Thiamin participates
in nerve tissue healing and nerve integration due to its newly shown function in the regulation of
heat hyperalgesia.1
The deficiency of thiamin causes a variety of pathologies connected to a nerve and
cognitive system development, cell metabolism, digestion, differentiation and proliferation, and
cell cycle function in several physiological functions.1 Thiamin supports the metabolism and cell
activity essential for tissue regeneration, brain activity, and organ function by regulating lactic
acid concentration. In the presence of thiamin deficiency, lactic acid concentration rises,
resulting in a fall in pH and cell damage. The consequences of this condition in humans include
difficulties in learning and memory, bradycardia, anorexia, coordination abnormalities, motor
function activity, as well as other neuro-mechanical flaws.4
Thiamin has a role in the absorption serotonin, that influences the functioning of the
hypothalamus, cerebellum, and hippocampus.2 Its deficit results in a variety of
neurodegenerative conditions and neurochemical disorders. Thiamin also plays a role in
preserving the function and structure of cerebellar cells; thiamin deficiency leads to impairment
to the thalamic areas manifesting as lesions in the cortex, stem, hippocampus, and cerebellum,
producing cognitive and motor impairment problems. Individuals with thiamin deficiency have
increased oxidative stress in their nervous tissues and neural systems due to the impaired control
of peroxidase enzymes in microglia brain cells. Thiamine deficiency is a medical illness caused
by thiamine insufficiency. Thiamine deficiency advances to beriberi, a more severe variant.3
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In conclusion, thiamin is a vital dietary component and an essential vitamin for typically
all species. This vitamin shortage results in decreased concentrations of various cellular
substrates created by TPP-dependent enzymes and elevated amounts of lactic acid.
Consequently, neurological, metabolic, and developmental issues may ensue, including
cerebellar, neurological, and brain abnormalities.
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References
1. Manzetti S, Zhang J, van der Spoel D. Thiamin Function, Metabolism, Uptake, and
Transport. Biochemistry. 2014;53(5):821-835. doi:10.1021/bi401618y
2. Rosenthal MD, Glew RH. Medical Biochemistry : Human Metabolism in Health and
Disease. Wiley-Blackwell; 2009.
3. Wiley KD, Mohit Gupta. Vitamin B1 Thiamine Deficiency (Beriberi). Nih.gov. Published
January 2, 2019. https://www.ncbi.nlm.nih.gov/books/NBK537204/
4. Dhir S, Tarasenko M, Napoli E, Giulivi C. Neurological, Psychiatric, and Biochemical
Aspects of Thiamine Deficiency in Children and Adults. Frontiers in Psychiatry. 2019;10.
doi:10.3389/fpsyt.2019.00207

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