Liver thiamin diphosphate

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). 

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... 

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. 

Vitamin Bi, also called thiamine, is required for all tissues and high concentrations are found in skeletal muscle, heart, liver, kidneys and brain. Thiamine diphosphate (TDP) is the active form and it serves as a cofactor for several enzymes involved in carbohydrate catabolism. These enzymes are also important in the biosynthesis of many cellular constituents, including neurotransmitters, and for the production of reducing equivalents used in oxidant stress defenses (Ba 2008). Thiamine is considered an anti-stress vitamin because it strengthens the immune system and improves the body s ability to withstand stress conditions (Haas 1988). 

Following absorption, thiamin is transported to the liver where it is phosphorylated under the action of ATP to form the coenzyme thiamin diphosphate (formerly called thiamin pyrophosphate or cocarboxylase), (see Fig. T-9) although this phosphorylation occurs rapidly in the liver, it is noteworthy that all nucleated cells appear to be capable of bringing about this conversion. 

Blair PV, Kobayashi R, Edwards HM 3rd, Shay NF, Baker DH, and Harris RA (1999) Dietary thiamin ievei influences levels of its diphosphate form and thiamin-dependent enzymic activities of rat liver./ournal ofNutrition 129, 641-8. 

The content of phosphorylated derivatives of thiamine has been investigated in a variety of tissues using Dowex-1 ion-exchange columns. The following proportions of thiamine and thiamine mono-, di-, and triphosphates were found in rat brain, heart, liver, and kidney thiamine 5%, monophosphate 10%, diphosphate 80%, and triphosphate 5%. The high levels of diphosphate are not surprising—diphosphate is the form in which the vitamin is active. But the presence of triphosphate remains unexplained because the role of triphosphate is not clear, and it has been suggested that triphosphate appears only when excessive amounts of thiamine are administered. 

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