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 three enzymes i.e. these enzymes use TTP to transfer an aldehyde unit to their substrates in various metabolic pathways. 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.
- Alpha 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 alpha 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.
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. 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.