Beriberi pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
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Overview
Pathophysiology
The active form of thiamine "thiamine pyrophosphate or TTP" is an essential cofactor for four enzymes i.e. these enzymes use TTP to transfer an aldehyde unit to their substrates in various metabolic pathways.[1] These enzymes are:
- Pyruvate dehydrogenase: involved in glycolysis (energy production) and synthesis of acetyl coA (the precursor for the neurotransmitter acetylcholine). Impaired activity leads to energy deprivation and deficient acetylcholine synthesis.
- α-ketoglutarate dehydrogenase: regulates oxidative phosphorylation and ATP production in the Krebs cycle. The Kreb's cycle is the main source of ATP production and is important for the synthesis of some neurotransmitters as the excitatory neurotransmitter (glutamate) and the inhibitory neurotransmitter (GABA). Therefore, impaired activity of α-ketoglutarate dehydrogenase leads of energy deprivation and deficient synthesis of glutamate and GABA neurotransmitters.
- Transketolase: involved in the hexose monophosphate shunt, which links glycolysis and pentose phosphate pathway. It is essential for the synthesis of nicotinamide adenine dinucleotide phosphate (NADPH), which is involved in intra-mitochondrial electron transport, as well as the synthesis of fatty acids ans steroids in the liver and adrenal gland. Impaired activity leads to energy deprivation.
- Branched-chain α-ketoacid dehydrogenase (BCKDH): catalyzes the oxidative decarboxylation of branched amino acids as leucine, isoleucine, and valine.This process generates acetyl coA and assists in the production of cholesterol and other neurotransmitters as glutamate and GABA.
Therefore, thiamine deficiency mainly affects the tissues that require high amounts of energy (ATP) as the heart and the brain. It is believed that energy deprivation and deficient neurotransmitter synthesis are responsible for the neural defects in dry beriberi. Other studies revealed non-coenzyme functions for thiamine in the brain as maintaining cell membrane stability and possibly acting as a trophic factor.[2] Although energy deprivation is also believed to be the main mechanism of wet beriberi, the full pathophysiological picture of this subtype is not yet fully elucidated.
References
- ↑ Singleton CK, Martin PR (2001). "Molecular mechanisms of thiamine utilization". Curr Mol Med. 1 (2): 197–207. doi:10.2174/1566524013363870. PMID 11899071.
- ↑ Bâ A (2008). "Metabolic and structural role of thiamine in nervous tissues". Cell Mol Neurobiol. 28 (7): 923–31. doi:10.1007/s10571-008-9297-7. PMID 18642074.