Disorders of Thiamine Metabolism

2016 ◽  
Author(s):  
Frédéric Sedel ◽  
Carla E. M. Hollak
Keyword(s):  
Plasma Membrane ◽  
Biosynthetic Pathway ◽  
Megaloblastic Anemia ◽  
Active Form ◽  
Pentose Phosphate ◽  
Water Soluble ◽  
Thiamine Pyrophosphate ◽  
Disease Mutations ◽  
Water Soluble Vitamin ◽  
Basal Ganglia Disease

Thiamine is a water-soluble vitamin acting in the mitochondria as a cofactor for energy metabolism and, in the cytoplasm, in the pentose phosphate biosynthetic pathway. Its transport through the plasma membrane requires two transporters with overlapping functions: THTR1 encoded by SLC19A2, and THTR2 encoded by SLC19A3. Thiamine is transformed into its active form, thiamine pyrophosphate (TPP) by a kinase encoded by the TPK1 gene. Then it may enter the mitochondria through a TPP transporter encoded by SLC25A19. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anemia (TRMA). Mutations in SLC19A3 cause biotin/thiamine–responsive basal ganglia disease. Mutations in SLC25A19 may cause early microcephaly with death in infancy (also called Amish microcephaly) or a later-onset bilateral striatal necrosis with progressive peripheral neuropathy. Recently, mutations in the TPK1 gene have been associated with recurrent encephalopathy with mild lactic acidosis.

Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2

2006 ◽  
Vol 291 (5) ◽  
pp. C851-C859 ◽  
Author(s):  
Veedamali S. Subramanian ◽  
Jonathan S. Marchant ◽  
Hamid M. Said
Keyword(s):  
Basal Ganglia ◽  
Cell Surface ◽  
Megaloblastic Anemia ◽  
Tissue Growth ◽  
Water Soluble ◽  
Transport Activity ◽  
Thiamine Transport ◽  
Sodium Dependent ◽  
Cast Doubt ◽  
Basal Ganglia Disease

The water-soluble micronutrient thiamine is required for normal tissue growth and development in humans. Thiamine is accumulated into cells through the activity of two cell surface thiamine transporters (hTHTR1 and hTHTR2), which are differentially targeted in polarized tissues. Mutational dysfunction of hTHTR1 is associated with the clinical condition of thiamine-responsive megaloblastic anemia: the symptoms of which are alleviated by thiamine supplementation. Recently, two hTHTR2 mutants (G23V, T422A) have been discovered in clinical kindreds manifesting biotin-responsive basal ganglia disease (BBGD): the symptoms of which are alleviated by biotin administration. Why then does mutation of a specific thiamine transporter isoform precipitate a disorder correctable by exogenous biotin? To investigate the suggestion that hTHTR2 can physiologically function as a biotin transporter, we examined 1) the cell biological basis of hTHTR2 dysfunction associated with the G23V and T422A mutations and 2) the substrate specificity of hTHTR2 and these clinically relevant mutants. We show that the G23V and T422A mutants both abrogate thiamine transport activity rather than targeting of hTHTR2 to the cell surface. Furthermore, biotin accumulation was not detectable in cells overexpressing either the full length hTHTR2 or the clinically relevant hTHTR2 mutants, yet was demonstrable in the same assay using cells overexpressing the human sodium-dependent multivitamin transporter, a known biotin transporter. These results cast doubt on the most parsimonious explanation for the BBGD phenotype, namely that hTHTR2 is a physiological biotin transporter.

scholarly journals Developmental maturation of the colonic uptake process of the microbiota-generated thiamin pyrophosphate

2021 ◽  
Author(s):  
Subrata Sabui ◽  
Jose M Romero ◽  
Hamid M Said
Keyword(s):  
Developmental Regulation ◽  
Cell Metabolism ◽  
Active Form ◽  
Vitamin B1 ◽  
Water Soluble ◽  
Biologically Active ◽  
Nuclear Factors ◽  
Water Soluble Vitamin ◽  
Uptake Process ◽  
Thiamin Pyrophosphate

The water-soluble vitamin B1 is essential for normal human health and physiology. In its main biologically active form, i.e., thiamin pyrophosphate (TPP), the vitamin plays many critical roles in cell metabolism; thus, its deficiency leads to a variety of adverse effects. Humans/mammals obtain vitamin B1 from two exogenous sources: diet and gut microbiota. Considerable amount of the microbiota-generated vitamin B1 exists in the form of TPP, and colonocytes can efficiently absorb this TPP via a high-affinity and specific carrier-mediated mechanism that involves the recently cloned colonic TPP transporter (cTPPT; product of SLC44A4 gene). There is nothing currently known about colonic uptake of TPP during early stages of life, and whether the process undergoes developmental regulation. We addressed this issue using the mouse as animal model. Our results showed that colonic uptake of TPP undergoes developmental up-regulation as the animal moves from the suckling period to weanling and adulthood. This up-regulation in uptake was found to be associated with a parallel induction in level of expression of the cTPPT protein, mRNA and heterologous nuclear RNA (hnRNA), suggesting possible involvement of transcriptional mechanism(s). We also found a parallel up-regulation in level of expression of the two nuclear factors that drive activity of the SLC44A4 promoter (i. e., CREB-1 and Elf-3) with maturation. These results demonstrate, for the first time, that colonic TPP uptake process and cTPPT expression are developmentally up-regulated, and that this up-regulation is likely driven via transcriptional mechanism(s).

scholarly journals A case report on hyperpigmentation in vitamin B12 deficiency

2019 ◽  
Vol 7 (5) ◽  
pp. 1944
Author(s):  
Vivek Kumar Verma ◽  
V. Vijayavarman
Keyword(s):  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Water Soluble ◽  
Animal Origin ◽  
Adequate Treatment ◽  
Cutaneous Manifestations ◽  
Food Of Animal Origin ◽  
Water Soluble Vitamin ◽  
B12 Deficiency

Cobalamin (Vitamin B12) is a water-soluble vitamin. Cobalamin is synthesized only by microorganisms. The only source of vitamin B12 for humans is food of animal origin. Hyperpigmentation of skin has been reported only rarely as the presenting manifestation of vitamin B12 deficiency. We report a patient who had hyperpigmentation as her presenting medical complaint and in whom Vitamin B12 deficiency was the cause.  A 36-year-old female presented with generalised weakness and progressive and asymptomatic hyperpigmentation of hand and feet for 5 months. She is vegetarian by diet. On examination, hyperpigmentation was present over dorsal aspect of metacarpophalangeal, proximal and distal interphalangeal joints. Hyperpigmentation were present over dorsum of the foot and over the joints. The tongue was depaillated, and hyperpigmentation was present. Her serum level of vitamin B12 was diminished (83pg/ml). Megaloblastic anemia presents with protean manifestations. The association between vitamin B12 deficiency and hyperpigmentation, although unusual, has been described. Cutaneous manifestations associated with B12 deficiency include characteristic mucocutaneous hyperpigmentation (most common), vitiligo, angular cheilitis, and hair-nail changes. It mainly affects knuckle pads and oral mucosa. It is an under-recognized sign of megaloblastic anemia and should always be looked for in the setting of pallor. Hyperpigmentation could be the earliest manifestation of vitamin B12 deficiency before anemia sets in. It is worthwhile to consider the possibility of vitamin B12 or folate deficiency in a patient with unexplained pigmentary changes. Early detection and adequate treatment will prevent anemia and various neurological manifestations.

scholarly journals Water-Soluble Vitamin Levels and Supplementation in Chronic Online Hemodiafiltration Patients

2020 ◽  
Vol 5 (12) ◽  
pp. 2160-2167 ◽  
Author(s):  
Nora Schwotzer ◽  
Michiko Kanemitsu ◽  
Sebastien Kissling ◽  
Roger Darioli ◽  
Mohammed Benghezal ◽  
...  
Keyword(s):  
Water Soluble ◽  
Water Soluble Vitamin

scholarly journals Perspective: Practical Approach to Preventing Subclinical B12 Deficiency in Elderly Population

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1913
Author(s):  
Alessandra Vincenti ◽  
Laura Bertuzzo ◽  
Antonio Limitone ◽  
Giuseppe D’Antona ◽  
Hellas Cena
Keyword(s):  
Vitamin B12 ◽  
Elderly Population ◽  
Vitamin B12 Deficiency ◽  
Water Soluble ◽  
Health Issues ◽  
Animal Products ◽  
Water Soluble Vitamin ◽  
Age Dependent ◽  
B12 Deficiency ◽  
Inadequate Dietary Intake

Vitamin B12 (also known as cobalamin) is an essential water-soluble vitamin that plays a pivotal role for several physiologic functions during one’s lifespan. Only certain microorganisms are able to synthetize B12, thus humans obtain cobalamin exclusively from their diet, specifically from animal-derived foods. Specific sub-group populations are at risk of vitamin B12 subclinical deficiency due to different factors including poor intake of animal source foods and age-dependent decrease in the capacity of intestinal B12 uptake. Consumption of animal products produces some negative health issues and negatively impacts sustainability while a plant-based diet increases the risk of B12 deficiency. Taking a cue from the aforementioned considerations, this narrative review aims to summarize facts about B12 deficiency and the burden of inadequate dietary intake in elderly population, as well as to discuss sustainable approaches to vitamin B12 deficiency in aging population.

Photoactive Water-Soluble Vitamin K: A Novel Amphiphilic Photoinduced Antibacterial Agent

2021 ◽  
Author(s):  
Zheng Zhang ◽  
Nicharee Wisuthiphaet ◽  
Nitin Nitin ◽  
Luxin Wang ◽  
Ryan Kawakita ◽  
...  
Keyword(s):  
Vitamin K ◽  
Antibacterial Agent ◽  
Water Soluble ◽  
Water Soluble Vitamin
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