Thiamine Pyrophosphate
Thiamine Monophosphate
Thiamine Triphosphate
Pyrithiamine
Wernicke Encephalopathy
Beriberi
Pyruvate Decarboxylase
Korsakoff Syndrome
Anemia, Megaloblastic
Alcohol Amnestic Disorder
Encephalomalacia
Phosphotransferases (Phosphate Group Acceptor)
Pyruvate Dehydrogenase Complex
Membrane Transport Proteins
Riboflavin
Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts. (1/735)
We have investigated the cellular pathology of the syndrome called thiamine-responsive megaloblastic anemia (TRMA) with diabetes and deafness. Cultured diploid fibroblasts were grown in thiamine-free medium and dialyzed serum. Normal fibroblasts survived indefinitely without supplemental thiamine, whereas patient cells died in 5-14 days (mean 9.5 days), and heterozygous cells survived for more than 30 days. TRMA fibroblasts were rescued from death with 10-30 nM thiamine (in the range of normal plasma thiamine concentrations). Positive terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining suggested that cell death was due to apoptosis. We assessed cellular uptake of [3H]thiamine at submicromolar concentrations. Normal fibroblasts exhibited saturable, high-affinity thiamine uptake (Km 400-550 nM; Vmax 11 pmol/min/10(6) cells) in addition to a low-affinity unsaturable component. Mutant cells lacked detectable high-affinity uptake. At 30 nM thiamine, the rate of uptake of thiamine by TRMA fibroblasts was 10-fold less than that of wild-type, and cells from obligate heterozygotes had an intermediate phenotype. Transfection of TRMA fibroblasts with the yeast thiamine transporter gene THI10 prevented cell death when cells were grown in the absence of supplemental thiamine. We therefore propose that the primary abnormality in TRMA is absence of a high-affinity thiamine transporter and that low intracellular thiamine concentrations in the mutant cells cause biochemical abnormalities that lead to apoptotic cell death. (+info)Cloning and characterization of the thiD/J gene of Escherichia coli encoding a thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase. (2/735)
A 1.7 kb DNA fragment isolated from an E. coli genomic library was able to complement the thiamin requirement of strains carrying the thiM, thiJ and thiD mutations. The three genes encode hydroxyethylthiazole kinase, hydroxymethylpyrimidine (HMP) kinase and phosphomethylpyrimidine (HMP-p) kinase, respectively. Sequence analysis revealed that the 1.7 kb fragment contained two ORFs of 708 bp and 801 bp. The former ORF complemented the thiM mutation and the latter ORF both the thiJ and thiD mutations. The latter ORF was cloned into the expression vector pET3a, and the encoded protein was purified through three successive column chromatographies. The purified protein was able to convert HMP to its monophosphate and the monophosphate to its pyrophosphate. These results suggest that the two distinct enzyme activities, HMP kinase and HMP-P kinase, are indeed a bifunctional enzyme encoded by a single gene, designated thiDIJ. (+info)Efficient sequence analysis of the six gene products (7-74 kDa) from the Escherichia coli thiamin biosynthetic operon by tandem high-resolution mass spectrometry. (3/735)
The 10(5) resolving power and MS/MS capabilities of Fourier-transform mass spectrometry provide electrospray ionization mass spectra containing >100 molecular and fragment ion mass values of high accuracy. Applying these spectra to the detection and localization of errors and modifications in the DNA-derived sequences of proteins is illustrated with the thiCEFSGH thiamin biosynthesis operon from Escherichia coli. Direct fragmentation of the multiply-charged intact protein ions produces large fragment ions covering the entire sequence; further dissociation of these fragment ions provides information on their sequences. For ThiE (23 kDa), the entire sequence was verified in a single spectrum with an accurate (0.3 Da) molecular weight (Mr) value, with confirmation from MS/MS fragment masses. Those for ThiH (46 kDa) showed that the Mr value (1 Da error) represented the protein without the start Met residue. For ThiF (27 kDa), MS/MS localized a sequence discrepancy to a 34 residue peptide. The first 107 residues of ThiC (74 kDa) were shown to be correct, with C-terminal heterogeneity indicated. For ThiG (predicted Mr = 34 kDa), ESI/FTMS showed two components of 7,310.74 (ThiS) and 26,896.5 Da (ThiG); MS/MS uncovered three reading frame errors and a stop codon for the first protein. MS/MS ions are consistent with 68 fragments predicted by the corrected ThiS/ThiG DNA sequences. (+info)Overexpression of recombinant proteins with a C-terminal thiocarboxylate: implications for protein semisynthesis and thiamin biosynthesis. (4/735)
A facile and rapid method for the production of protein C-terminal thiocarboxylates on DNA-encoded polypeptides is described. This method, which relies on the mechanism of the cleavage reaction of intein-containing fusion proteins, can produce multi-milligram quantities of protein C-terminal thiocarboxylate quickly and inexpensively. The utility of this method for protein semisynthesis and implications for studies on the biosynthesis of thiamin are discussed. (+info)Dietary thiamin level influences levels of its diphosphate form and thiamin-dependent enzymic activities of rat liver. (5/735)
This study was prompted by our incomplete understanding of the mechanism responsible for the clinical benefits of pharmacological doses of thiamin in some patients with maple syrup urine disease (MSUD) and the question of whether thiamin diphosphate (TDP), a potent inhibitor of the activity of the protein kinase that phosphorylates and inactivates the isolated branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, affects the activity state of the complex. Rats were fed a chemically-defined diet containing graded levels of thiamin (0, 0.275, 0.55, 5.5, and 55 mg thiamin/kg diet). Maximal weight gain was attained over a 3-wk period only in rats fed diets with 5.5 and 55 mg thiamin/kg. Feeding rats the thiamin-free diet for just 2 d caused loss of nearly half of the TDP from liver mitochondria. Three more days caused over 70% loss, an additional 3 wk, over 90%. Starvation for 2 d had no effect, suggesting a mechanism for conservation of TDP in this nutritional state. Mitochondrial TDP was higher in rats fed pharmacological amounts of thiamin (55 mg thiamin/kg diet) than in rats fed adequate thiamin for maximal growth. Varying dietary thiamin had marked but opposite effects on the activities of alpha-ketoglutarate dehydrogenase (alpha-KGDH) and BCKDH. Thiamin deficiency decreased alpha-KGDH activity, increased BCKDH activity, and increased the proportion of BCKDH in the active, dephosphorylated, state. Excess dietary thiamin had the opposite effects. TDP appears to be more tightly associated with alpha-KGDH than BCKDH in thiamin-deficient rats, perhaps denoting retention of alpha-KGDH activity at the expense of BCKDH activity. Thus, thiamin deficiency and excess cause large changes in mitochondrial TDP levels that have a major influence on the activities of the keto acid dehydrogenase complexes. (+info)Thiamine repression and pyruvate decarboxylase autoregulation independently control the expression of the Saccharomyces cerevisiae PDC5 gene. (6/735)
The Saccharomyces cerevisiae gene PDC5 encodes the minor isoform of pyruvate decarboxylase (Pdc). In this work we show that expression of PDC5 but not that of PDC1, which encodes the major isoform, is repressed by thiamine. Hence, under thiamine limitation both PDC1 and PDC5 are expressed. PDC5 also becomes strongly expressed in a pdc1delta mutant. Two-dimensional gel electrophoresis of whole protein extracts shows that thiamine limitation stimulates the production of THI gene products and of Pdc5p. Deletion of PDC1 only stimulates production of Pdc5p. We conclude that the stimulation of PDC5 expression in a pdc1delta mutant is not due to a response to thiamine limitation. (+info)Rereplication phenomenon in fission yeast requires MCM proteins and other S phase genes. (7/735)
The fission yeast Schizosaccharomyces pombe can be induced to perform multiple rounds of DNA replication without intervening mitoses by manipulating the activity of the cyclin-dependent kinase p34(cdc2). We have examined the role in this abnormal rereplication of a large panel of genes known to be involved in normal S phase. The genes analyzed can be grouped into four classes: (1) those that have no effect on rereplication, (2) others that delay DNA accumulation, (3) several that allow a gradual increase in DNA content but not in genome equivalents, and finally, (4) mutations that completely block rereplication. The rereplication induced by overexpression of the CDK inhibitor Rum1p or depletion of the Cdc13p cyclin is essentially the same and requires the activity of two minor B-type cyclins, cig1(+) and cig2(+). In particular, the level, composition, and localization of the MCM protein complex does not alter during rereplication. Thus rereplication in fission yeast mimics the DNA synthesis of normal S phase, and the inability to rereplicate provides an excellent assay for novel S-phase mutants. (+info)Characterization and hormonal modulation of immunoreactive thiamin carrier protein secreted by adult rat Leydig cells in vitro. (8/735)
Leydig cells isolated from adult rats and maintained under defined conditions in culture secrete a protein of molecular weight (Mr) 70 000 which is immunologically similar to chicken thiamin carrier protein (TCP). Synthesis of immunoreactive TCP by these cells is demonstrated by immunoprecipitation of [35S]methionine incorporated, newly synthesized proteins with monoclonal and polyclonal antibodies to chicken TCP. The amount of immunoreactive TCP secreted into the culture supernatant is quantitated by using a specific radioimmunoassay. Under the influence of LH, secretion of immunoreactive TCP is enhanced 3-fold and can be inhibited by up to 70% with aromatase inhibitor (1,4,6-androstatrien-3,17-dione). Cyclic AMP acts as a second messenger in the sequence of events involved in LH-induced elevation of immunoreactive TCP in Leydig cells. The effects of exogenous estradiol-17beta and diethylstilbestrol are comparable in terms of stimulation of secretion of immunoreactive TCP by these cells. Tamoxifen brought about a 70% decrease in the elevated levels of immunoreactive TCP. These results suggest that estrogen mediates immunoreactive TCP induction in hormonally stimulated adult rat Leydig cells. (+info)Thiamine, also known as vitamin B1, is a water-soluble vitamin that plays a crucial role in certain metabolic reactions, particularly in the conversion of carbohydrates into energy in the body. It is essential for the proper functioning of the heart, nerves, and digestive system. Thiamine acts as a cofactor for enzymes involved in the synthesis of neurotransmitters and the metabolism of carbohydrates, lipids, and proteins. Deficiency in thiamine can lead to serious health complications, such as beriberi (a disease characterized by peripheral neuropathy, muscle wasting, and heart failure) and Wernicke-Korsakoff syndrome (a neurological disorder often seen in alcoholics due to chronic thiamine deficiency). Thiamine is found in various foods, including whole grains, legumes, pork, beef, and fortified foods.
Thiamine pyrophosphate (TPP) is the active form of thiamine (vitamin B1) that plays a crucial role as a cofactor in various enzymatic reactions, particularly in carbohydrate metabolism. TPP is essential for the functioning of three key enzymes: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase. These enzymes are involved in critical processes such as the conversion of pyruvate to acetyl-CoA, the oxidative decarboxylation of alpha-ketoglutarate in the Krebs cycle, and the pentose phosphate pathway, which is important for generating reducing equivalents (NADPH) and ribose sugars for nucleotide synthesis. A deficiency in thiamine or TPP can lead to severe neurological disorders, including beriberi and Wernicke-Korsakoff syndrome, which are often observed in alcoholics due to poor nutrition and impaired thiamine absorption.
Thiamine monophosphate (TMP) is a biochemical compound that is a derivative of thiamine (vitamin B1). It is a cofactor for several enzymes involved in key metabolic processes, particularly in the conversion of carbohydrates into energy. TMP plays an essential role in the metabolism of carbohydrates, amino acids, and neurotransmitters.
Thiamine monophosphate is formed when thiamine undergoes phosphorylation by the enzyme thiamine pyrophosphokinase. This reaction adds a phosphate group to the thiamine molecule, resulting in the formation of TMP. Thiamine monophosphate can then be further phosphorylated to form thiamine triphosphate (TTP) or dephosphorylated back to thiamine.
Deficiency in thiamine and its derivatives, including TMP, can lead to several medical conditions, such as beriberi, Wernicke-Korsakoff syndrome, and other neurological disorders. These conditions are often associated with impaired energy metabolism, nerve damage, and cognitive decline. Proper intake of thiamine through diet or supplementation is crucial for maintaining normal physiological functions and preventing these health issues.
Thiamine triphosphate (TTP) is not a widely recognized or used medical term in the context of defining a specific disease, condition, or diagnostic marker. However, thiamine, also known as vitamin B1, is an essential nutrient that plays a crucial role in various bodily functions, including nerve function and energy metabolism.
Thiamine triphosphate (TTP) is a biochemical compound formed from thiamine and adenosine triphosphate (ATP). TTP acts as a cofactor for several enzymes involved in the metabolism of carbohydrates, amino acids, and neurotransmitters. Its exact physiological role and significance are still under investigation, but it is believed to have a role in neuronal excitability, synaptic plasticity, and energy homeostasis.
In summary, Thiamine Triphosphate (TTP) is a biochemical compound that plays a role in various metabolic processes, particularly in the nervous system. However, it does not have a specific medical definition as a disease or condition.
Pyrithiamine is not typically considered a medical term, but it is a chemical compound that has been used in scientific research. It's an antivitamin, specifically an analog of thiamine (vitamin B1), which means it can interfere with the metabolism of thiamine in the body.
Here's a more specific definition from a biochemical perspective:
Pyrithiamine is a synthetic organic compound with the formula C6H7N2O2S. It is an analog of thiamine, where the aminomethyl group of thiamine is replaced by a pyridine ring. This structural modification makes pyrithiamine unable to act as a vitamin, but it can still interact with the enzymes and transport proteins involved in thiamine metabolism. As a result, pyrithiamine has been used as a tool to study thiamine deficiency and its effects on various organisms, including mammals.
Please note that pyrithiamine is not a term commonly used in clinical medicine or patient care. If you have any concerns about vitamins, nutrition, or health-related topics, it's best to consult a healthcare professional for accurate information and advice tailored to your specific situation.
Oxythiamine is not a medication or a condition, but rather a chemical compound. It is an oxidized form of thiamine (vitamin B1), which means it has been changed by the addition of oxygen molecules. Oxythiamine is used in research to study the effects of thiamine deficiency and to investigate the role of thiamine in various biological processes. It is not used as a medication in humans or animals.
Wernicke Encephalopathy is a neuropsychiatric disorder that is caused by a deficiency of thiamine (vitamin B1). It is characterized by a classic triad of symptoms: confusion, oculomotor dysfunction (such as nystagmus and ophthalmoplegia), and gait ataxia. Other symptoms can include memory loss, apathy, and hypothermia.
Wernicke Encephalopathy is most commonly seen in alcoholics due to poor nutrition, but it can also occur in people with conditions that cause malabsorption or increased thiamine requirements, such as AIDS, cancer, and chronic diarrhea. Immediate treatment with thiamine replacement therapy is necessary to prevent progression of the disease and potential permanent neurological damage. If left untreated, Wernicke Encephalopathy can lead to Korsakoff's syndrome, a chronic memory disorder.
Amprolium is an antiprotozoal medication used primarily in veterinary medicine to prevent and treat coccidiosis, which is a parasitic infection caused by protozoa of the Eimeria species. It works as a competitive inhibitor of thiamine (vitamin B1) absorption in the coccidian parasites, leading to their eventual death. Amprolium is available in various formulations, including powders, pellets, and solutions, for use in animals such as chickens, turkeys, and calves. It is not typically used in human medicine.
Beriberi is a medical condition caused by a deficiency in thiamine (vitamin B1). This deficiency can lead to various symptoms, including peripheral neuropathy, muscle wasting, and heart failure. There are two main types of beriberi: wet beriberi, which affects the cardiovascular system, and dry beriberi, which primarily affects the nervous system.
Wet beriberi can cause symptoms such as shortness of breath, rapid heart rate, and fluid accumulation in the legs and lungs. Dry beriberi, on the other hand, is characterized by symptoms such as numbness, tingling, and weakness in the hands and feet, muscle wasting, and difficulty walking.
Beriberi can be prevented through a balanced diet that includes adequate amounts of thiamine-rich foods, such as whole grains, legumes, pork, beef, and fortified cereals. Treatment for beriberi typically involves administering thiamine supplements to restore normal levels of the vitamin in the body. In severe cases, hospitalization may be necessary to provide supportive care and monitor the patient's condition.
Pyruvate decarboxylase is an enzyme that plays a crucial role in the cellular process of fermentation and gluconeogenesis. In medical and biochemical terms, pyruvate decarboxylase is defined as:
"An enzyme (EC 4.1.1.1) that catalyzes the decarboxylation of pyruvate to form acetaldehyde and carbon dioxide in the presence of thiamine pyrophosphate (TPP) as a cofactor. This reaction occurs during anaerobic metabolism, such as alcohol fermentation in yeast or bacteria, and helps to generate ATP and NADH for the cell's energy needs."
In humans, pyruvate decarboxylase is primarily found in the liver and kidneys, where it participates in gluconeogenesis – the process of generating new glucose molecules from non-carbohydrate precursors. The enzyme's activity is essential for maintaining blood glucose levels during fasting or low-carbohydrate intake.
Deficiencies in pyruvate decarboxylase can lead to metabolic disorders, such as pyruvate decarboxylase deficiency (PDC deficiency), which is characterized by lactic acidosis, developmental delays, and neurological issues. Proper diagnosis and management of these conditions often involve monitoring enzyme activity and glucose metabolism.
Korsakoff syndrome is a neuropsychiatric disorder typically caused by alcohol abuse, specifically thiamine (vitamin B1) deficiency in the brain. It's often associated with Wernicke encephalopathy, and the two together are referred to as Wernicke-Korsakoff syndrome.
The main features of Korsakoff syndrome include severe memory impairment, particularly anterograde amnesia (inability to form new memories), confabulation (making up stories due to gaps in memory), and a lack of insight into their condition. Other cognitive functions like intelligence and perception are usually preserved.
The syndrome is believed to result from damage to the mammillary bodies and other structures in the diencephalon, particularly the thalamus. Treatment involves abstinence from alcohol, thiamine replacement, and a balanced diet. The prognosis varies but often includes some degree of permanent memory impairment.
Megaloblastic anemia is a type of macrocytic anemia, which is characterized by the presence of large, structurally abnormal, and immature red blood cells called megaloblasts in the bone marrow. This condition arises due to impaired DNA synthesis during erythropoiesis (the process of red blood cell production), often as a result of deficiencies in vitamin B12 or folate, or from the use of certain medications that interfere with DNA synthesis.
The hallmark feature of megaloblastic anemia is the presence of megaloblasts in the bone marrow, which exhibit an asynchrony between nuclear and cytoplasmic maturation. This means that although the cytoplasm of these cells may appear well-developed, their nuclei remain underdeveloped and fragmented. As a result, the peripheral blood shows an increase in mean corpuscular volume (MCV), reflecting the larger size of the red blood cells.
Additional hematological findings include decreased reticulocyte counts, neutrophil hypersegmentation, and occasionally thrombocytopenia or leukopenia. Neurological symptoms may also be present due to the involvement of the nervous system in vitamin B12 deficiency.
Megaloblastic anemia is typically treated with supplementation of the deficient vitamin (B12 or folate), which helps restore normal erythropoiesis and alleviate symptoms over time.
Alcohol Amnestic Disorder is not listed as a separate disorder in the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is used by mental health professionals to diagnose mental conditions. However, it was previously included in earlier editions as a subtype of Amnestic Disorder due to the effects of substance use or exposure to toxins.
Alcohol Amnestic Disorder is characterized by significant memory impairment that is directly caused by alcohol consumption. This disorder can result in anterograde amnesia, which is the inability to form new memories after drinking, and/or retrograde amnesia, which involves forgetting previously learned information or personal experiences.
The diagnosis of Alcohol Amnestic Disorder typically requires a comprehensive medical and neuropsychological evaluation to determine the extent and nature of memory impairment, as well as to rule out other potential causes for cognitive decline. Treatment usually involves a combination of abstinence from alcohol, pharmacotherapy, and psychosocial interventions to address substance use disorder and any co-occurring mental health conditions.
Encephalomalacia is a medical term that refers to the softening and degeneration of brain tissue. It is typically caused by an injury, infection, or lack of oxygen supply to the brain. This condition can lead to various neurological symptoms depending on the location and extent of the damage in the brain. Encephalomalacia may result in cognitive impairments, motor function loss, speech difficulties, and other long-term disabilities. Treatment options vary based on the underlying cause and severity of the condition but often include rehabilitation therapies to help manage symptoms and improve quality of life.
The Pyruvate Dehydrogenase Complex (PDC) is a multi-enzyme complex that plays a crucial role in cellular energy metabolism. It is located in the mitochondrial matrix and catalyzes the oxidative decarboxylation of pyruvate, the end product of glycolysis, into acetyl-CoA. This reaction links the carbohydrate metabolism (glycolysis) to the citric acid cycle (Krebs cycle), enabling the continuation of energy production in the form of ATP through oxidative phosphorylation.
The Pyruvate Dehydrogenase Complex consists of three main enzymes: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3). Additionally, two regulatory enzymes are associated with the complex: pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP). These regulatory enzymes control the activity of the PDC through reversible phosphorylation and dephosphorylation, allowing the cell to adapt to varying energy demands and substrate availability.
Deficiencies or dysfunctions in the Pyruvate Dehydrogenase Complex can lead to various metabolic disorders, such as pyruvate dehydrogenase deficiency, which may result in neurological impairments and lactic acidosis due to disrupted energy metabolism.
Membrane transport proteins are specialized biological molecules, specifically integral membrane proteins, that facilitate the movement of various substances across the lipid bilayer of cell membranes. They are responsible for the selective and regulated transport of ions, sugars, amino acids, nucleotides, and other molecules into and out of cells, as well as within different cellular compartments. These proteins can be categorized into two main types: channels and carriers (or pumps). Channels provide a passive transport mechanism, allowing ions or small molecules to move down their electrochemical gradient, while carriers actively transport substances against their concentration gradient, requiring energy usually in the form of ATP. Membrane transport proteins play a crucial role in maintaining cell homeostasis, signaling processes, and many other physiological functions.
Riboflavin, also known as vitamin B2, is a water-soluble vitamin that plays a crucial role in energy production and cellular function, growth, and development. It is essential for the metabolism of carbohydrates, fats, and proteins, and it helps to maintain healthy skin, hair, and nails. Riboflavin is involved in the production of energy by acting as a coenzyme in various redox reactions. It also contributes to the maintenance of the mucous membranes of the digestive tract and promotes iron absorption.
Riboflavin can be found in a variety of foods, including milk, cheese, leafy green vegetables, liver, kidneys, legumes, yeast, mushrooms, and almonds. It is sensitive to light and heat, so exposure to these elements can lead to its degradation and loss of vitamin activity.
Deficiency in riboflavin is rare but can occur in individuals with poor dietary intake or malabsorption disorders. Symptoms of riboflavin deficiency include inflammation of the mouth and tongue, anemia, skin disorders, and neurological symptoms such as confusion and mood changes. Riboflavin supplements are available for those who have difficulty meeting their daily requirements through diet alone.