Acetyl-CoA and acetylcholine metabolism in nerve terminal compartment of thiamine deficient rat brain.
Summary of "Acetyl-CoA and acetylcholine metabolism in nerve terminal compartment of thiamine deficient rat brain."
Abstract The decrease of pyruvate and ketoglutarate dehydrogenase complex activities is the main cause of energy and acetyl-CoA deficits in thiamine deficiency-evoked cholinergic encephalopathies. However, disturbances in pathways of acetyl-CoA metabolism leading to appearance of cholinergic deficits remain unknown. Therefore, the aim of this work was to investigate alterations in concentration and distribution of acetyl-CoA and in acetylcholine metabolism in brain nerve terminals, caused by thiamine deficits. They were induced by the pyrithiamine, a potent inhibitor of thiamine pyrophosphokinase. The thiamine deficit reduced metabolic fluxes through pyruvate and ketoglutarate dehydrogenase steps, yielding deficits of acetyl-CoA in mitochondrial and cytoplasmic compartments of K-depolarized nerve terminals. It also inhibited indirect transport of acetyl-CoA though ATP-citrate lyase pathway being without effect on its direct Ca-dependent transport to synaptoplasm. Resulting suppression of synaptoplasmic acetyl-CoA correlated with inhibition of quantal acetylcholine release (r=0.91, p=0.012). On the other hand, thiamine deficiency activated nonquantal acetylcholine release that was independent of shifts in intraterminal distribution of acetyl-CoA. Choline acetyltransferase activity was not changed by these conditions. These data indicate that divergent alterations in the release of nonquantal and quantal acetylcholine pools from thiamine deficient nerve terminals could be caused by the inhibition of acetyl-CoA and citrate synthesis in their mitochondria. They in turn, caused inhibition of acetyl-CoA transport to the synaptoplasmic compartment through ATP-citrate lyase pathway yielding deficits of cholinergic functions.
Department of Laboratory Medicine,Medical University of Gda?sk, Poland.
This article was published in the following journal.
Name: Journal of neurochemistry
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20649840
- DOI: http://dx.doi.org/10.1111/j.1471-4159.2010.06919.x
Brain thiamine homeostasis has an important role in energy metabolism and displays reduced activity in Alzheimer's disease (AD). Thiamine deficiency (TD) induces regionally specific neuronal death in ...
Cell growth requires fatty acids for membrane synthesis. Fatty acids are assembled from 2-carbon units in the form of acetyl-CoA (AcCoA). In nutrient and oxygen replete conditions, acetyl-CoA is predo...
Cells sense and appropriately respond to the physical conditions and availability of nutrients in their environment. This sensing of the environment and consequent cellular responses are orchestrated ...
The purpose of this study was to find the effect of endurance training and thiamine supplementation on anti-fatigue during the exercise. Each nine students from K Women's University went through three...
In adults, the lateral pterygoid muscle (LPM) is usually divided into the upper and lower head, between which the buccal nerve passes. Recent investigations have demonstrated foetal developmental chan...
The purpose of this study is to determine whether Acetyl L-carnitine can prevent the development of nerve damage, known as neuropathy, in individuals taking anti-HIV drugs over a 48-week p...
There are different treatments for nausea and vomiting in pregnancy. According to the ACOG recommendations, promethazine is the first line of parenteral treatment after oral treatment had ...
Heart failure remains an increasing cause of morbidity and mortality in the United States even in the face of recent advances in the treatment of cardiovascular disease. There is an urgent...
The major goal of this project is to determine whether the use of thiamine in patients with septic shock will result in attenuation of lactic acidosis and a more rapid reversal of shock.
The study is performed to consider the effect of thiamine supplementation on symptoms and signs of patients with heart failure and systolic and diastolic function of left ventricle.
Medical and Biotech [MESH] Definitions
Veterinary coccidiostat that interferes with thiamine metabolism. It may cause thiamine deficiency.
A hexosiminidase that specifically hydrolyzes terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-beta-D-galactosaminides.
An enzyme present in nerve tissue. It catalyzes reversibly the formation of thiamine diphosphate and orthophosphate from thiamine triphosphate. EC 220.127.116.11.
An enzyme that hydrolyzes thiamine pyrophosphate to thiamine monophosphate plus inorganic phosphate. EC 3.6.1.-.
A thiamine antagonist due to its inhibition of thiamine pyrophosphorylation. It is used to produce thiamine deficiency.