Thiamine pyrophosphate

Enzymatic decarboxylation of α-keto acids was first described by Neuberg in 1911 ^[3] , who demonstrated that an extract from yeast breaks pyruvic acid into acetaldehyde and carbon dioxide. However, if the yeast was previously washed with an alkaline phosphate buffer, then such an extract did not exhibit decarboxylating activity, however, the activity was restored by adding boiled extract of fresh yeast. The thermostable extract factor necessary for the enzymatic decarboxylation of pyruvic acid was called cocarboxylase ( co- enzyme carboxylase ).

In 1926, Jansen and Donat isolated thiamine in their pure form ^[4] , in 1937, Loman and Schuster isolated pure “cocarboxylase” - a dialyzable cofactor of oxidative decarboxylation of pyruvic acid with yeast enzymes ^[5] , it was identified as a thiamine derivative - thiamine pyrophosphate.

The reaction center in thiamine is the carbon atom in position 2 of the thiazole ring. The thiazole fragment of thiamine is a quaternary thiazolium salt quaternized at the nitrogen atom. Thiazole salts unsubstituted at position 2 are capable of losing a proton with the formation of ylides.

Such ylides are capable of reacting with the carbonyl groups of keto acids and aldehydes to form the corresponding 2-thiazolylcarbinols. These compounds are intermediates in various enzymatic reactions. So, for example, pyruvic acid and other α-keto acids react with thiamine pyrophosphate, forming the corresponding carbinols - addition products, which are then quickly decarboxylated and cleaved, forming aldehydes and the starting thiamine pyrophosphate:

CF 1.2.1.58 phenylglyoxalate dehydrogenase (acylating)

phenylglyoxalate + NAD ⁺ + CoA-SH = benzoyl-S-CoA + CO ₂ + NADH

CF 1.2.2.2 pyruvate dehydrogenase (cytochrome)

pyruvate + ferricytochrome b ₁ + H ₂ 0 = acetate + CO ₂ + ferricytochrome b ₁

EC 1.2.3.3 pyruvate oxidase

pyruvate + phosphate + O ₂ = acetyl phosphate + CO ₂ + H ₂ O ₂

CF 1.2.4.1 pyruvate dehydrogenase (lipoamide)

Component of pyruvate dehydrogenase complex

KF 1.2.4.2 oxyglutarate dehydrogenase (lipoamide)

Component of pyruvate dehydrogenase complex

KF 1.2.4.4 3-methyl-2-oxobutyrate dehydrogenase (lipoamide)

CF 1.2.7.1 pyruvate synthase

KF 1.2.7.7 2-oxoisovalerate ferredoxin reductase:

KF 1.2.7.8 indolylpyruvate ferredoxin oxidoreductase:

KF 1.2.7.9 2-oxoglutarate ferredoxin oxidoreductase

CF 2.2.1.1 transketolase

sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-ribose 5-phosphate + D-xylulose 5-phosphate

CF 2.2.1.3 formaldehyde transketolase

D-xylulose-5-phosphate + formaldehyde = glyceraldehyde 3-phosphate + glyceron

EC 2.2.1.4 acetoin — ribose-5-phosphate transaldolase

3-hydroxybutan-2-one + D-ribose-5-phosphate = acetaldehyde + 1-deoxy-D-altro-heptulose-7-phosphate

CF 2.2.1.5 2-hydroxy-3-oxoadipate synthase

2-oxoglutarate + glyoxylate = 2-hydroxy-3-oxoadipate + CO ₂

KF 2.2.1.6 acetolactate synthase

2 pyruvate = 2-acetolactate + CO ₂

EC 2.2.1.7 1-deoxy-D-xylulose-5-phosphate synthase

pyruvate + D-glyceraldehyde-3-phosphate = 1-deoxy-D-xylulose-5-phosphate + CO ₂

CF 2.5.1.64 6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate synthase

2-oxoglutarate + isochorizmate (1S, 6R) -6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate + pyruvate + CO

KF 2.7.4.15 thiamine diphosphate kinase

ATP + thiamine diphosphate = ADP + thiamine triphosphate

CF 2.7.4.16 thiamine phosphate kinase

ATP + thiamine phosphate = ADP + thiamine diphosphate

CF 2.7.6.2 thiamine diphosphokinase

ATP + thiamine = AMP + thiamine diphosphate

CF 3.6.1.15 nucleoside triphosphatase

NTP + H ₂ 0 = NDP + phosphate

CF 3.6.1.28 thiamine triphosphatase

thiamine triphosphate + H ₂ 0 = thiamine diphosphate + phosphate

CF 4.1.1.1 pyruvate decarboxylase

2-oxo acid = aldehyde + CO ₂

also catalyzes the formation of acyloins from aldehydes

KF 4.1.1.7 benzoyl formate decarboxylase

benzyl formate = benigidalzald + CO ₂

EC 4.1.1.8 oxalyl-CoA decarboxylase

oxalyl-CoA = formyl-CoA + CO ₂

CF 4.1.1.71 2-oxoglutarate decarboxylase

2-oxoglutarate = succinic acid semi-aldehyde + CO ₂

CF 4.1.1.74 indolylpyruvate decarboxylase

3- (indol-3-yl) pyruvate = 2- (indol-3-yl) acetaldehyde + CO ₂

CF 4.1.1.75 5-guanidino-2-oxopentanoate decarboxylase

5-guanidino-2-oxo-pentanoate = 4-guanidinobutanal + CO ₂

KF 4.1.1.79 sulfopyruvate decarboxylase

3-sulfo-pyruvate = 2-sulfoacetaldehyde + CO ₂

CF 4.1.2.9 phosphoketolase

D-xylulose-5-phosphate + phosphate = acetyl phosphate + D-glyceraldehyde-3-phosphate + H ₂ 0

CF 4.1.2.38 benzoin aldolase

2-hydroxy-1,2-diphenylethanone = 2 benzaldehyde

It is used in medicine under the name "cocarboxylase." Synonyms: Berolase, Bioxilasi, B-Neuran, Cobilasi, Cocarbil, Cocarbosyl, Cocarboxylase, Coenzyme B, Cothiamine, Diphosphothiamin, Pyruvodehydrase, etc.

Cocarboxylase is usually used as a component of complex therapy. It is administered intramuscularly, sometimes under the skin or intravenously. ^[2]

Cocarboxylase reduces pain in angina pectoris , has an antiarrhythmic effect, and reduces acidosis in diabetes. ^[1] It has a regulatory effect on metabolic processes; reduces the level of lactic and pyruvic acid in the body, improves glucose uptake; improves trophic nerve tissue, helps normalize the function of the cardiovascular system. ^[6]

The biological effect of cocarboxylase differs from thiamine, so, for example, it is ineffective with beriberi (B1-vitamin deficiency). ^[7]

It is applied in the following cases: ^{[2] [6] [7]}

• hyperglycemic coma , precomatous state and acidosis in diabetes
• metabolic and respiratory acidosis in chronic cardiopulmonary syndrome
• respiratory failure
• heart rhythm disturbance (extrasystole, bigeminia, paroxysmal tachycardia, atrial fibrillation)
• liver or kidney failure
• coronary insufficiency
• myocardial infarction
• mild forms of multiple sclerosis
• preeclampsic conditions
• eclampsia
• alcohol poisoning and chronic alcoholism
• poisoning by digitalis, barbiturates and other metabolites by oxidation
• auxiliary for diphtheria, scarlet fever, typhoid and paratyphoid

For medical use, cocarboxylase is available as cocarboxylase hydrochloride (0.05 g) for injection (Socarboxylasi hydrochlridum 0.05 pro injectionibus). It is a lyophilized dry porous mass of white color with a slight specific smell. The drug is hygroscopic, readily soluble in water (pH 2.5% solution 1.2 - 1.9). Solutions are prepared aseptically immediately before use. ^[2]