Acetyl-CoA and acetylcholine metabolism in nerve terminal compartment of thiamine deficient rat brain.

06:00 EDT 24th July 2010 | BioPortfolio

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.

Journal Details

This article was published in the following journal.

Name: Journal of neurochemistry
ISSN: 1471-4159


DeepDyve research library

PubMed Articles [9651 Associated PubMed Articles listed on BioPortfolio]

Treatment of genetic defects of thiamine transport and metabolism.

Thiamine is a key cofactor for energy metabolism in brain tissue. There are four major genetic defects (SLC19A2, SLC19A3, SLC25A19 and TPK1) involved in the metabolism and transport of thiamine throug...

α7 nicotinic acetylcholine receptor-deficient mice exhibit sustained attention impairments that are reversed by β2 nicotinic acetylcholine receptor activation.

Disruptions of executive function, including attentional deficits, are a hallmark of a number of diseases. Acetylcholine in the prefrontal cortex (PFC) regulates attentive behaviour; however the role ...

Correlat ion of thiamine metabolite levels with cognitive function in the non-demented elderly.

Thiamine metabolism is critical for glucose metabolism and also vital for brain function, which is susceptible to decline in the elderly. This study aimed to investigate whether thiamine metabolites c...

Biochemical changes correlated with blood thiamine and its phosphate esters levels in patients with diabetes type 1 (DMT1).

Thiamine (vitamin B1) is an essential enzyme cofactor in most organisms required at several stages of anabolic and catabolic intermediary metabolism. However, little is known on the positive effects o...

AβPP-Transgenic 2576 Mice Mimic Cell Type-Specific Aspects of Acetyl-CoA-Linked Metabolic Deficits in Alzheimer's Disease.

The pyruvate-derived acetyl-CoA is a principal direct precursor substrate for bulk energy synthesis in the brain. Deficits of pyruvate dehydrogenase in the neocortex are common features of Alzheimer's...

Clinical Trials [2302 Associated Clinical Trials listed on BioPortfolio]

ALCAR Prophylaxis Study

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...

Thiamine Supplement in Patients With Severe Hyperthyroidism

Thyrotoxicosis is a hypermetabolic state in which there is increased utilization of thiamine. Thiamine deficiency has been observed in association with hyperthyroidism. Several studies doc...

A Pilot Study Investigating the Effects of Acetyl-L-Carnitine and Vincristine-Induced Neuropathy in Pediatric Patients With ALL

The purpose of this study is to see if a drug called Acetyl-L-Carnitine can help prevent painful nerve damage and nerve pain which is caused by vincristine, a drug used in chemotherapy in ...

Does Thiamine Help Vomiting and Nausea in Pregnancy?

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 ...

Thiamine and Acute Decompensated Heart Failure: Pilot Study

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...

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

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.

Quick Search

DeepDyve research library

Relevant Topic

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Searches Linking to this Article