Thiamine kinase

In humans, thiamine is both actively and passively absorbed to a limited level in the intestines, is transported as the free vitamin, is then taken up in actively metabolizing tissues, and is converted to the phosphate esters via ubiquitous thiamine kinases. During thiamine deficiency all tissues stores are readily mobilhed. Because depletion of thiamine levels in erythrocytes parallels that of other tissues, erythrocyte thiamine levels ate used to quantitate severity of the deficiency. As deficiency progresses, thiamine becomes indetectable in the urine, the primary excretory route for this vitamin and its metaboHtes. Six major metaboHtes, of more than 20 total, have been characterized from human urine, including thiamine fragments (7,8), and the corresponding carboxyHc acids (1,37,38). 

Uptake and Metabolism. A saturable active transport system in the jejunum provides efficient uptake of the vitamin into the intestinal mucosa cell. Thiamine kinase in the intestinal mucosa cell transfers a pyrophosphate from the ATP to the propyl alcohol at po-... 

ATP thiamin phosphotransferase kinase, thiamin (phosphorylating) thiamin kinase... 

Melnick, J. et al (2004) Identification of the two missing bacterial genes involved in thiamine salvage thiamine pyrophosphokinase and thiamine kinase. J. Bacterial, 186 (11), 3660-3662. 

After injection of [ Cj-labelled thiamin to rats, it was found that, in the brain, the incorporation of radioactivity was slower into ThDP than into ThMP and ThTP (Gaitonde and Evans 1983). As ThDP is the most likely precursor of the two other derivatives (thiamin kinase activity has never been... 

In those organisms able to synthesize thiamin, the endpoint of synthesis is ThMP. In enterobacteria, such as E. coli, ThMP can then be phosphorylated to ThDP by thiamin phosphate kinase (EC 2.7.4.16). Thiamin taken up from the extracellular medium is first phosphorylated to ThMP by thiamin kinase (EC 2.7.1.89). In thiamin-synthesizing eukaryotes such as fungi and plants, ThMP is dephosphorylated to thiamin by phosphatases. Thiamin is then pyropho-sphorylated to ThDP by TPK. 

Thiamine, thiamine diphosphate. Humans are not able to synthesize the thiazol ring, the key element of thiamine. Therefore thiamine must be supplied from the diet (daily allowance is 1.0-1.5 mg). It is converted to the active compound thiamine diphosphate (vitamin Bi) by thiamine kinases present in all tissues. 

Thiamine is metabolized to TPP by thiamine pyrophosphokinase (EC 2.1.62) in animal cells including red and white blood cells. This enzyme is also present in plants, yeast, and a bacterium (Paracoccus denitrificans) (7). However, in some bacteria, for example in Escherichia coli, thiamine is metabolized to TPP by a two-step reaction catalyzed by thiamine kinase (EC 2.7.1.89) and TMP kinase (EC 2.7.4.10). Thiamine pyrophosphate is further metabolized to TI P in yeast, animal tissues, and human red blood cells. Evidence has been obtained which indicates that cytosolic adenylate kinase (EC 2.7.4.3) catalyzes TIP synthesis from TPP in vitro (8) and in vivo (3). The enzyme system involved in thiamine metabolism to TTP in human red blood cells was recently identified, purified, and reconstituted (9). 

Biosynthesis of pyrophosphate (5) from pyrimidine phosphate (47) and thia2ole phosphate (48) depends on the activity of five en2ymes, four of them kinases (87). In yeasts and many other organisms, including humans, pyrophosphate (5) can be obtained from exogenous thiamine in a single step cataly2ed by thiamine pyrophosphokinase (88). 

The PDHC catalyzes the irreversible conversion of pyruvate to acetyl-CoA (Fig. 42-3) and is dependent on thiamine and lipoic acid as cofactors (see Ch. 35). The complex has five enzymes three subserving a catalytic function and two subserving a regulatory role. The catalytic components include PDH, El dihydrolipoyl trans-acetylase, E2 and dihydrolipoyl dehydrogenase, E3. The two regulatory enzymes include PDH-specific kinase and phospho-PDH-specific phosphatase. The multienzyme complex contains nine protein subunits, including... 

The hypE proteins are 302-376 residues long and appear to consist of three domains. Domain 1 shows sequence identity to a domain from phosphoribosyl-aminoimida-zole synthetase which is involved in the fifth step in de novo purine biosynthesis and to a domain in thiamine phosphate kinase which is involved in the synthesis of the cofactor thiamine diphosphate (TDP). TDP is required by enzymes which cleave the bond adjacent to carbonyl groups, e.g. phosphoketolase, transketolase or pyruvate decarboxylase. Domain 2 also shows identity to a domain found in thiamine phosphate kinase. Domain 3 appears to be unique to the HypF proteins. 

The answer is B. While all of the listed conditions are consistent with lethargy and developmental defects, the lactic acidosis rules out pyruvate kinase deficiency. Thiamine and niacin deficiencies are unlikely due to the lack of effect of vitamin supplementation. Excess pyruvate is the source of the elevated alanine in the serum. The clinical findings are thus consistent with pyruvate carboxylase deficiency, which is associated with severe hypoglycemia due to fasting due to impaired gluconeogenesis. 

Glycine max (L.) Merrill G. soja Sieb. Zucc. Da Dou Ye Da Dou (Soybean) (seed) Protein, isoflavone derivatives, genisteine, daidzein, riboflavin, thiamine, niacin, pantothenic acid, choline.33,67 Phytoestrogenic, elevate the vasomotor system, prevent cancer, a potent inhibitor of protein tyrosine kinase. 

S ATP + 2-methyl-4-amino-5-pho.sphomethylpyrimidine <1, 2, 3> (<1> specific for ATP [1] <3> enzyme has both 2-methyl-4-amino-5-hydroxy-methylpyrimidine phosphate kinase and thiamin-phosphate diphosphatase activities, involved in thiamine biosynthesis [3]) (Reversibility <1, 2, 3> [1,2, 3]) [1,2,3]... 

Reddick, J.J. Kinsland, C. Nicewonger, R. Christian, T Downs, D.M. Winkler, M.E. Begley, T.P. Overexpression, purification and characterization of two pyrimidine kinases involved in the biosynthesis of thiamin 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase and 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase. Tetrahedron, 54, 15983-15991 (1998)... 

Shikata, H. Koyama, S. Egi, Y Yamada, K. Kawasaki, T. Identification of creatine as a cofactor of thiamin-diphosphate kinase. FEES Lett., 201, 101-104 (1986)... 

Yamaguchi, T. Uchimura, K. Mishiro, N. Watanabe, K. Evidence for the presence of thiamin diphosphate kinase in human erythrocytes. JPN. J. Toxicol. Environ. Health, 42, 524-528 (1996)... 

ATP thiamin-phosphate phosphotransferase kinase, thiamin monophosphate (phosphorylating) thiamin monophosphatase... 

Nishino, H. Biogenesis of cocarboxylase in Escherichia coli. Partial purification and some properties of thiamine monophosphate kinase. J. Biochem., 72, 1093-1100 (1972)... 

Webb, E. Downs, D. Characterization of thiL, encoding thiamin-monophosphate kinase, in Salmonella typhimurium. J. Biol. Chem., 272, 15702-15707 (1997)... 

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