Specific Vitamins as Cofactors Thiamine Vitamin B1

Best known as the anti-beriberi factor and called at first simply vitamin B by McCollum, thiamine was shown to be involved in the decarboxylation of pyruvate to acetaldehyde in alcohol fermentation and was named 'cocarboxylase' in 1932.

Table 1 Vitamins and nonvitamin cofactorsa

Name of vitamina

Related coenzymes

Biochemical function

Thiamine, thiamin B1 Riboflavin B2 Niacin (nicotinamide) B3 Pantothenic acid B5 Pyridoxine B6 Folic acid (folacin) B9 Cobalamin B12 L-Ascorbic acid C Calciferol D Tocophoral E Biotin H

Phylloquinone K Bioflavonoids P Nonvitamin cofactors p-Aminobenzoate a-Lipoic acid Betaine Coenzyme Q PQQ




S-adenosyl methionine Glutathione

3' Phosphoadenosine-5' phosphosulfate




Coenzyme A

Pyridoxal 5' phosphate


5' Deoxyadenosyl cobalamin


















Carbonyl group transfer

Redox reactions

Redox reactions

Acyl group transfer

Amine group transfer

One-carbon transfer

Methylation, rearrangement reactions

Collagen, adrenaline synthesis

Calcium absorption


CO2 fixation

Prothrombin synthesis


One-carbon transfer Acetyl group transfer Methylating agent Electron transfer Oxidation reactions Oxidation reactions Fatty acid transfer Membrane lipids Methylation reactions Group transfer, anitoxidant Sulfate esterification aAlthough codified in vitamin literature at one time, B4, B10, and B11 have since been abandoned.

[ Proteins ] [ Carbohydrates j ( Lipids ]

Amino acids


Fatty acids & glycerol

Fatty acids & glycerol


Figure 1 Occurrence of organic cofactors in energy metabolism. Only a few key intermediates in the pathway are shown. Dotted circle shows reactions taking place in the mitochondria. Note how coenzymes NAD+ and FAD cycle between oxidized and reduced forms.


Figure 1 Occurrence of organic cofactors in energy metabolism. Only a few key intermediates in the pathway are shown. Dotted circle shows reactions taking place in the mitochondria. Note how coenzymes NAD+ and FAD cycle between oxidized and reduced forms.

Confirmation of its structure as TPP came 5 years later. Its name is meant to signify a vitamin containing sulfur (thios in Greek).


1. Pyruvate dehydrogenase complex in mitochondria.

2. a-Ketoglutarate dehydrogenase complex in mitochondria.

3. Branch chain dehydrogenase.

4. Transketolase reactions in pentose pathway and in reductive pentose pathway of photosynthesis.

Reactivity The structure of thiamine has two rings bridged by a methylene group as seen in Figure 2A. The coenzyme (TPP) arises via an ATP-dependent pyrophosphorylation of the primary alcohol group (Figure 2B). What may be called the active site of the coenzyme is the carbon in position 2 (C-2) of the smaller five-member thiazolium ring (arrow). A favorable positioning of C-2 between atoms of nitrogen and sulfur causes C-2 hydrogen to exchange protons with water, indicating C-2 can ionize to a carbanion. As a carbanion, C-2 is able to engage positive centers such as carbonyl carbons of a-keto acids and keto sugars. In the reaction with pyruvate, a-ketoglutarate, or branch-chain a-keto acids from valine, leucine, or isoleucine, a carboxyl group is

Table 2 Sample of enzymes associated with each of the coenzymes derived from vitamins



1. Thiamine-pyrophosphate

5. Pyridoxal-5' phosphate

6. Tetrahydrofolate

7. Biocytin

8. Coenzyme A (pantothenic acid)

9. Cobalamin

10. L-Ascorbate

Pyruvate dehydrogenase complex a-Ketoglutarate dehydrogenase complex Transketolase

Branch chain dehydrogenase Glyceraldehyde-3-PO4

dehydrogenase Pyruvate dehydrogenase complex Alcohol dehydrogenase Lactate dehydrogenase Glucose-6-PO4 dehydrogenase Glutamate dehydrogenase 3-Ketoacyl-ACP synthase Glucose-6-PO4 dehydrogenase Succinate dehydrogenase Fatty acyl-CoA dehydrogenase Aminotransferases Glycogen phosphorylase Glycine synthase Homocysteine methyltransferase Pyruvate carboxylase Acetyl-CoA carboxylase Propionyl-CoA carboxylase Pyruvate dehydrogenase complex Acetyl-CoA carboxylase Citrate synthase Homocysteine methyltransferase Methylmalonyl-CoA mutase Prolyl and lysyl hydroxylase Dopamine-^-monooxygenase expelled as CO2 and the electrons remain with the 'active aldehyde' on the C-2 position. Attack on a keto sugar cleaves the first two carbons as a unit, which then attaches to C-2 as an 'active glycoalde-hyde' adduct. Yeast disengage active aldehyde as acetaldehyde later to be reduced to ethanol by alcohol dehydrogenase. Bacteria convert 'active aldehyde' to acetyl-phosphate. In the mitochondria of higher organisms, however, active aldehyde is oxidized by an FAD-containing enzyme (part of the pyruvate dehydrogenase complex) and transferred to lipoic acid (see Figure 10), which transfers the highly energetic acetyl group to the thiol group of coen-zyme A. As a coenzyme for transketolases in the pentose pathway, TPP takes part in the formation of ribose-5-phosphate, glyceraldehyde-3-phosphate, and erythrose-4-phosphate from sedohepulose-7-phosphate, xyulose-5-phosphate, and fructose-6-phosphate, respectively. Each sugar phosphate donates an 'active glycoaldehyde' to an aldose acceptor.

TPP is also the coenzyme for branch chain dehydrogenase, the enzyme that catalyzes the oxidative decarboxylation of a-keto acids derived from leucine, isoleucine, and valine, three essential amino acids. The reaction follows a scheme similar to pyu-vate oxidation, only this time the carbon skeleton of the amino acid condenses with coenzyme A (CoA).

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