Thiamin pentose phosphate pathway

A number of lyases are known which, unlike the aldolases, require thiamine pyrophosphate as a cofactor in the transfer of acyl anion equivalents, but mechanistically act via enolate-type additions. The commercially available transketolase (EC 2.2.1.1) stems from the pentose phosphate pathway where it catalyzes the transfer of a hydroxyacetyl fragment from a ketose phosphate to an aldehyde phosphate. For synthetic purposes, the donor component can be replaced by hydroxypyruvate, which forms the reactive intermediate by an irreversible, spontaneous decarboxylation. 

Thiamine pyrophosphate Is an essential coenzyme for several critical metabolic enzymes—PDH, a-ketoglutarate dehydrogenase, and transketolase of the pentose phosphate pathway. 

Vitamin B1 (thiamine) has the active form, thiamine pyrophosphate. It is a cofactor of enzymes catalyzing the conversion of pyruvate to acetyl CoA, a-ketoglutarate to succinyl CoA, and the transketolase reactions in the pentose phosphate pathway. A deficiency of thiamine causes beriberi, with symptoms of tachycardia, vomiting, and convulsions. In Wernicke-Korsakoff syndrome (most common in alcoholics), individuals suffer from apa thy, loss of memory, and eye movements. There is no known toxicity for this vitamin. 

Ketols can also be formed enzymatically by cleavage of an aldehyde (step a, Fig. 14-3) followed by condensation with a second aldehyde (step c, in reverse). An enzyme utilizing these steps is transketolase (Eq. 17-15),132b which is essential in the pentose phosphate pathways of metabolism and in photosynthesis. a-Diketones can be cleaved (step d) to a carboxylic acid plus active aldehyde, which can react either via a or c in reverse. These and other combinations of steps are often observed as side reactions of such enzymes as pyruvate decarboxylase. A related thiamin-dependent reaction is that of pyruvate and acetyl-CoA to give the a-diketone, diacetyl, CH3COCOCH3.133 The reaction can be viewed as a displacement of the CoA anion from acetyl-CoA by attack of thiamin-bound active acetaldehyde derived from pyruvate (reverse of step d, Fig. 14-3 with release of CoA). 

Some bacteria that lack the usual aldolase produce ethanol and lactic acid in a 1 1 molar ratio via the "heterolactic fermentation." Glucose is converted to ribulose 5-phosphate via the pentose phosphate pathway enzymes. A thiamin diphosphate-dependent "phosphoketolase" cleaves xylulose 5-phosphate in the presence of inorganic phosphate to acetyl phosphate and glyceraldehyde 3-phosphate. 

Thiamine pyrophosphate also plays a key role in the biosynthetic reactions that build (or degrade) pentoses from hexoses. We have mentioned these reactions previously in connection with the Calvin cycle (Section 20-9) and the pentose-phosphate pathway (Section 20-10C). 

Later studies established the coenzyme role of thiamin diphosphate in transketolase in the pentose phosphate pathway. More recent studies have shown that thiamin triphosphate acts to regulate a chloride channel in nerve tissue. 

The third phase of the Calvin cycle is the regeneration of ribulose 1,5-bisphosphate, the acceptor of CO2 in the first step. The problem is to construct a five-carbon sugar from six-carbon and three-carbon sugars. A transketolase and an aldolase play the major role in the rearrangement of the carbon atoms. The transketolase, which we will see again in the pentose phosphate pathway (Section 20.2.3). requires the coenzyme thiamine pyrophosphate (TPP) to transfer a two-carbon unit (CO-CH2OH) from a ketose to an aldose. 

FIGURE 9.71 Pentose phosphate pathway. The pentose phosphate pathway is used for the metabolism of various sugars. It is required for the biosynthesis of ribose 5-phosphate (a component of ATP, GTP, CTP, UTP, TTP, and the nucleic acids). The pentose phosphate pathway is used for the reduction of NADP. Thiamin pyrophosphate is a cofactor for two enzymes of the pathway, as indicated by TPP. The circled groups are the two-carbon units transferred by TPP. 

Thiamine pyrophosphate (Figure 4-8A) is involved in decarboxylation of a-keto acids and is the cofactor for the transketolase of the pentose phosphate pathway. 

In the pentose phosphate pathway, thiamine pyrophosphate is required for the action of... 

A. The transketolase of the pentose phosphate pathway requires thiamine pyrophosphate. 

The most commonly used enzyme for the functional assay is transketolase. Transketolase catalyzes two reactions in the pentose phosphate pathway (Figure 30-10). As an enzyme within the erythrocyte, transketolase is independent of nonspecific changes in the extracellular plasma. As vitamin Bi deficiency becomes more severe, (1) thiamine becomes limiting in the body cells, (2) the amount of the coenzyme is depleted, and (3) the transketolase activity sub-... 

Thiamine pyrophosphate is also an important cofactor for the transketolase reactions in the pentose phosphate pathway of carbohydrate metabolism (Fignre 15-3). These reactions are important in the reversible transformation of pentoses into the glycolytic intermediates fructose 6-phosphate and glyc-eraldehyde 3-phosphate. Again, it is the reactive carbon on the thiazole ring of TPP that reacts with a ketose phosphate (xylnlose 5-phosphate) to canse the release of an aldose phosphate with two fewer carbons (glyceraldehyde 3-phosphate). The TPP-bonnd glycoaldehyde unit is then transferred to a different aldose phosphate (ribose 5-phosphate or erythrose 4-phosphate) to produce a ketose phosphate that has two carbons more (sedoheptulose 7-phosphate or fructose 6-phosphate). 

Thiamine pyrophosphate is also an important cofactor for many dehydrogenase reactions as well as the transketolase reactions in the pentose phosphate pathway of carbohydrate metabolism. 

The pentose phosphate pathway (PPP) is the major pathway for recycling nicotinamide adenine dinucleotide (NAD) to nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and for the production of ribose-5-phosphate that is needed for the synthesis of nucleotides. The function of the PPP depends on the synthesis of nicotinamide-adenine dinucleotide phosphate (NADP) and thiamin pyrophosphate, a coenzyme... 

TK is one of the enzymes involved in the oxidative pentose phosphate pathway, and requires the cofactors thiamine pyrophosphate (TPP)12191 and Mg2+[218). It reversibly transfers the C1-C2 ketol unit from D-xylulose 5-phosphate to D-ribose 5-phosphate, and generates D-sedoheptulose 7-phosphate and D-Gly 3-P. D-Erythrose 4-phosphate also functions as an acceptor of the ketol unit from D-xylulose 5-phosphate, to produce Fru 6-P and D-Gly 3-P (Fig. 14.2-1). TK from baker s yeast is commercially available, and the enzyme can also be isolated from spinach[220, 2211 TK from E. coli has been overexpressed and prepared on a large scale12221. In ketol transfer reactions,... 

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