Thiamine, Thiamine Phosphates, and Their Metabolizing Enzymes in Human Brain

@article{Bettendorff1996ThiamineTP,
  title={Thiamine, Thiamine Phosphates, and Their Metabolizing Enzymes in Human Brain},
  author={Lucien Bettendorff and Frank Mastrogiacomo and Stephen J. Kish and Thierry Grisar},
  journal={Journal of Neurochemistry},
  year={1996},
  volume={66}
}
Abstract: Total thiamine (the sum of thiamine and its phosphate esters) concentrations are two‐ to fourfold lower in human brain than in the brain of other mammals. There were no differences in the total thiamine content between biopsied and autopsied human brain, except that in the latter, thiamine triphosphate was undetectable. The main thiamine phosphate‐metabolizing enzymes could be detected in autopsied brain, and the kinetic parameters were comparable to those reported in other species… 

Brain thiamine, its phosphate esters, and its metabolizing enzymes in alzheimer's disease

Although the magnitude of the TDP reduction is slight, a chronic subclinical TDP deficiency could contribute to impaired brain function in AD and might provide the basis for the modest improvement by thiamine in cognitive status of some patients with AD.

Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease

The results imply that an imbalance of phosphorylation-dephosphorylation related to thiamine and glucose metabolism may be a potential target for AD prevention and therapy.

Thiamine Status in Humans and Content of Phosphorylated Thiamine Derivatives in Biopsies and Cultured Cells

A novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation.

Low Thiamine Diphosphate Levels in Brains of Patients with Frontal Lobe Degeneration of the Non‐Alzheimer's Type

Results suggest that decreased contents of TDP, which is essentially mitochondrial, is a specific feature of FNAD, and provides a basis for a trial of thiamine, to improve the cognitive status of the patients.

Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain*

The results show for the first time that a high energy triphosphate compound other than ATP can be produced by a chemiosmotic type of mechanism, and might shed a new light on the understanding of the mechanisms of thiamine deficiency-induced brain lesions.

Brain levels of thiamine and its phosphate esters in Friedreich's ataxia and spinocerebellar ataxia type 1

In FA, brain thiamine concentrations are normal, whereas in SCA1 the levels are, at most, only slightly reduced, a finding that might be related to the severe neuronal damage in this brain area.

Thiamine triphosphate: a ubiquitous molecule in search of a physiological role

In some tissues where adenylate kinase activity is high and ThTPase is absent, ThTP accumulates, reaching ≥ 70 % of total thiamine, with no obvious physiological consequences, raising the possibility that ThTP is part of a still uncharacterized cellular signaling pathway.

Molecular Characterization of a Specific Thiamine Triphosphatase Widely Expressed in Mammalian Tissues*

The recombinant ThTP enzyme had properties similar to those of human brain ThTPase, and it was specific for ThTP, and the mRNA was expressed in most human tissues but at relatively low levels.

High thiamine diphosphate level as a protective factor for Alzheimer’s disease

Blood TDP levels were significantly decreased in female AD patients compared to male AD patients, and its protective efficacy may be independent of other metabolic factors.
...

References

SHOWING 1-10 OF 74 REFERENCES

Distribution of Thiamine, Thiamine Phosphates, and Thiamine Metabolizing Enzymes in Neuronal and Glial Cell Enriched Fractions of Rat Brain

Thiamine and thiamine mono‐ and pyrophosphate were present in neuronal enriched fractions at concentrations 2.8‐fold higher in neuronal than in glial fractions, whereas the levels of TPKase, UMPase, IMPase, IDPase, UDPase, and TPPase were 2.0‐, 2.2‐, 1.3‐, 3.7‐, and 20.6 times higher than inglial fractions.

Thiamine phosphatases in human brain: regional alterations in patients with alcoholic cirrhosis.

Increased TDP degradation resulting from increased activities of TDPase could contribute to the pathophysiological mechanisms involved in alcohol-related brain dysfunction.

Content of thiamin phosphate esters in mammalian tissues--an extremely high concentration of thiamin triphosphate in pig skeletal muscle.

An extremely high concentration of thiamin triphosphate (TTP) was detected in adult pig skeletal muscles and may give a clue as to the physiological functions of TTP.

Metabolism of Thiamine Triphosphate in Rat Brain: Correlation with Chloride Permeability

The results suggest that TTP synthesis is catalyzed by an ATP:TDP transphosphorylase rather than by the cytoplasmic adenylate kinase that may be present in the vesicles and a regulatory role of TTP on chloride permeability, but the target remains to be characterized.

Low Energy Levels in Thiamine‐Deficient Encephalopathy

It is suggested that a low energy state is closely related to the formation of edematous lesions in thiamine-deficient encephalopathy.

Brain glutamate and γ-aminobutyrate (GABA) metabolism in thiamin-deficient rats

Investigation of the brain metabolism of glutamate and γ-aminobutyrate in thiamin-deficient and pair-fed control rats found a marked circumannual variation, with a peak in mid-summer and a minimum value inMid-winter, suggesting a considerable increase in the metabolic flux through the GABA shunt inThiamin deficiency.

Distribution of the α‐ketoglutarate dehydrogenase complex in rat brain

These data are the first to demonstrate KGDHC immunoreactivity in discrete areas of rat brain and are vital to the understanding of selective vulnerability to metabolic insults and disease.
...