Liver thiamin

Beyond pharmaceutical screening activity developed on aminothiazoles derivatives, some studies at the molecular level were performed. Thus 2-aminothiazole was shown to inhibit thiamine biosynthesis (941). Nrridazole (419) affects iron metabohsm (850). The dehydrase for 5-aminolevulinic acid of mouse liver is inhibited by 2-amino-4-(iS-hydroxy-ethyl)thiazole (420) (942) (Scheme 239). l-Phenyl-3-(2-thiazolyl)thiourea (421) is a dopamine fS-hydroxylase inhibitor (943). Compound 422 inhibits the enzyme activity of 3, 5 -nucleotide phosphodiesterase (944). The oxalate salt of 423, an analog of levamisole 424 (945) (Scheme 240),... 

Classic beri-beri, rarely seen in the United States and Europe, except in alcoholism (P4), is endemic in the Far East because of the prevalent diet of decorticated rice (F6). It occurs in two forms wet beri-beri, characterized by edema and cardiovascular symptoms (G6), and dry beri-beri with peripheral neuritis, paralysis, and atrophy of the muscles. Conditions which may predispose to deficiency by increasing thiamine requirements are pregnancy (see section 2.4), and lactation, hyperthyroidism, malignant disease, febrile conditions, increased muscular activity, high carbohydrate diets, and parenteral administration of glucose solutions. A constant supply of thiamine is required for optimal nutrition because storage in the liver and elsewhere is limited. Thiamine is synthesized by bacteria in the intestinal tract of various animals, but this is not a dependable source for man. 

The clinical significance of thiamine and its necessity for pyruvic acid oxidation has been discussed. Recent reports concerning the coenzyme function of thiamine in pentose (H13), tryptophan (D2), and lipoic acid metabolism (R6) have increased our knowledge of thiamine in metabolism and lend added interest to the role of thiamine in clinical problems. This method has also been used to assay thiamine in liver and brain. 

Lactobacillus plantarum is a reliable reagent for pantothenate in foods, tissues, and biologic fluids (M4, T5). It is also useful in studying the pantothenic acid content of tissues, in particular the liver. As with thiamine, the pantothenic acid levels in serum of the mother at term, although higher than in other individuals, are 5 times less than the fetus... 

A8. Anonymous, Thiamine and liver lipids. Nutrition Revs. 19, 21-22 (1961). 

When the patient is manifesting acute symptoms of withdrawal such as the shakes, a rapid pulse, or increased blood pressure, then detoxification with a benzodiazepine should begin immediately. When the patient s liver function is unknown, we recommend lorazepam (1-2 mg) as the treatment of choice in the emergency room setting. The lorazepam can be repeated every hour until the patient s symptoms begin to resolve. Initial treatment should also include vitamin supplements as noted earlier, especially thiamine. 

Substance-Induced Dementias. Substances of abuse can also cause dementia. The most common is alcohol-related dementia. Chronic alcoholism leads to dementia in several ways. The poor diet of the alcoholic causes a deficiency of certain essential nutrients such as thiamine. The alcoholic often suffers recurrent head injuries from falls or altercations. Alcohol-induced liver failure can expose the brain to toxic injury. Finally, the direct toxic effects of alcohol itself on the brain can lead to dementia. In addition to alcohol, the abuse of inhalants such as paint thinner and... 

Alcoholics may have both decreased intake and decreased absorption of thiamine. Liver disease can prevent the formation of the active coenzyme. 

Pharmacokinetics Metabolized to thiamine pyrophosphate (active) in the liver. At dietary levels thiamine is completely distributed to tissues. At pharmacologic doses, excess thiamine is excreted in urine. 

Alcohol is toxic to the liver, and prolonged use results in cirrhosis, a condition in which scar tissue replaces normal liver tissue, and impairs the ability of the liver to function. Ghronic use can also result in permanent damage to the GNS, partly due to a poor diet regimen and diminished intake of vitamin B1 (thiamine). 

Thiamin is widespread in many nutritious foods but pig meat, liver, whole-grain cereals, legumes and nuts are particularly rich sources. Because of its importance in energy metabolism, the RDA for thiamin is quoted in terms of energy intake (0.12mgkJ 1 day-1 1 mg day-1 minimum). This is approximately equivalent to 1.5 mg and 1.1 mg per day for men and women, respectively. The RNI value for thiamin is 0.4 mg per 1000 kcal (4186 kJ) per day for adults. 

Ruenwongsa, P. Cooper, J.R. The role of bound thiamine pyrophosphate in the synthesis of thiamine triphosphate in rat liver. Biochim. Biophys. Acta, 482, 64-70 (1977)... 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

The terpenes, carotenoids, steroids, and many other compounds arise in a direct way from the prenyl group of isopentenyl diphosphate (Fig. 22-1).16a Biosynthesis of this five-carbon branched unit from mevalonate has been discussed previously (Chapter 17, Fig. 17-19) and is briefly recapitulated in Fig. 22-1. Distinct isoenzymes of 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) in the liver produce HMG-CoA destined for formation of ketone bodies (Eq. 17-5) or mevalonate.7 8 A similar cytosolic enzyme is active in plants which, collectively, make more than 30,000 different isoprenoid compounds.910 However, many of these are formed by an alternative pathway that does not utilize mevalonate but starts with a thiamin diphosphate-dependent condensation of glyceraldehyde 3-phosphate with pyruvate (Figs. 22-1,22-2). 

M Hagg, J Kumpulainen. Thiamine and riboflavin contents in Finnish pig, heifer, and cow livers and in pork loin. J Food Comp Anal 7 301-306, 1994. 

Storage in body Substantial primarily in liver, adipose tissue not found in all tissues Little or no storage (except vitamin B12 and possibly thiamin)... 

A 43-year-old woman was admitted to hospital in December feeling unwell with a two-week history of urinary symptoms. She had decompensated cirrhosis of her liver on ultrasound and was taking pentoxifylline (oxpentifylline, Trental), co-amoxiclav, omeprazole and thiamine. She was jaundiced and confused with respiratory failure limiting speech to partial sentences. There was a marked deterioration in liver function overnight and she went into acute renal failure. 

Thiamine is given for alcohol-induced liver toxicity (to prevent Wernicke s encephalopathy). 

Small quantities of thiamin are present in almost all foods of plant and animal origin. Good sources are whole cereal grains organ meats such as liver, heart, and kidney lean pork eggs nuts and potatoes (Table 9-16). Although thiamin content is usually mea-... 

When sulphur dioxide dissolves, the disulphide chemical bonds which result destroy the vitamin B or thiamine in foods by breaking up the protein molecules. Sulphurous acid, produced when sulphur dioxide is dissolved, may cause gastric irritation. Healthy people have no problem metabolising sulphur dioxide the kidneys and liver both produce enzymes which oxidise sulphites, but those with impaired kidney and liver may need to avoid sulphites. Foods containing sulphites may precipitate an asthmatic attack in asthma sufferers, who are very sensitive to the irritant effects of sulphur dioxide gas which may be liberated from the foods containing it and inhaled as the food is swallowed. It is one of the additives which the Hyperactive Children s Support Group recommends is eliminated from the diets of the children it represents. ... 

The reaction mixture contained 80 /xL of 130 mM Hepes-67 mM Tris buffer (pH 7.4) 10 ju,L each (to give final concentration of 1 mM) of NAD, thiamine pyrophosphate, coenzyme A, MgCl2, and dithiothreitol 20 /xL of tissue extract or enzyme source, and 30 /xL of bovine serum albumin (1 mg). The reaction was started by adding 20 fiL of a-ketoglutarate to give a final concentration of 10 mM After incubation at 30°C for 1, 5, or 20 minutes for purified enzyme from bovine heart, brain, or liver mitochondria, or platelet homogenates, the reaction was stopped by addition of 20 /xL of 60% perchloric acid and the denatured protein was removed by centrifugation. A 10 /xL aliquot was used for HPLC analysis. 

In vitro, thiamin diphosphate inhibits the kinase that phosphorylates and inactivates branched-chain oxo-acid dehydrogenase, and might be expected to increase the activity of the enzyme in tissues, thus offering an alternative mechanism for thiamin-responsive maple syrup urine disease. However, this seems not to be relevant in vivo, possibly because tissue concentrations of thiamin diphosphate do not rise high enough to affect the activity of the kinase. In thiamin-deficient animals, there is an increase in the total liver content... 

Newaz MA, Yousefipour Z, Nawa NN (2005) Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid protection from free radical injury. Qin Exp Hypertens 27(6) 497-508 Nunn JF, Chanarin I, Taimer AG, Owen ER (1986) Megaloblastic bone marrow changes after repeated nitrous oxide anaesthesia. Reversal with fofinicacid. Br J Anaesth 58(12) 1469-1470 Parker WD Jr, Hass R, Stumpf DA, Parks J, Eguren LA, Jackson C (1984) Brain mitochondrial metabolism in experimental thiamine deficiency. Neurology 34(11) 1477-1481... 

Both free thieimin and thiamin monophosphate circulate in plasma about 60% of the total is the monophosphate. Under normcd conditions, most is hound to edbumin when the cdbumin binding capacity is saturated, the excess is rapidly filtered at the glomerulus and excreted in the urine. Although a significemt eimount of newly absorbed thiamin is phosphorylated in the liver, edl tissues Ccm take up both thieimin and thicunin monophosphate, emd eue ahle to phosphorylate them to thiamin diphosphate cmd thieimin triphosphate. In most tissues, it is free thiamin that is the immediate precursor of thiamin diphosphate, which is formed by a pyrophosphokinase both the p-emd y-phosphates of ATP are incorporated. Thicunin monophosphate euises mairdy eis a result of sequentied hydrolysis of thicunin triphosphate and thieunin diphosphate. 

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