emDocs - October 24, 2017 - Authors: Reyes J and Baker A
Edited by: Singh M and Koyfman A
"...The multi-organ manifestations of thiamine deficiency can be explained by the essential role of thiamine in the body’s most basic metabolic processes. Thiamine pyrophosphate or thiamine diphosphate is a coenzyme in the pyruvate dehydrogenase complex, which accelerates the conversion of pyruvate to acetyl coenzyme A. This process links anaerobic glycolysis to the aerobic Krebs cycle which produces 36 mol of adenosine triphosphate (ATP) from 1 mol of glucose.
When thiamine is not available to facilitate these reactions, energy production is limited to the comparatively paltry 2 mol of ATP produced via anaerobic metabolism. Thiamine is also a cofactor for alpha-ketoglutarate dehydrogenase (also of the Krebs cycle) and transketolase (of the pentose phosphate pathway) in which essential nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate (NADH and NADPH) are created for use in energy production and reductive biosynthesis.4,7 Thiamine deficiency therefore results in massive energy deficits and defects in cell synthesis, replication, and repair.
In the central nervous system, decreased acetylcholine synthesis results in impaired conduction, and mitochondrial dysfunction from oxidative stress leads to neurodegeneration. In the peripheral nerve and muscle tissues, this leads to decreased sensorimotor activity, muscle atrophy, and neuropathy. In cardiac muscle, lack of thiamine shifts pyruvate toward increased lactate production, resulting in a dysfunctional myocardium..."