Biochemical significance of water soluble vitamins, cofactors derived from these vitamins

Water-soluble vitamins play essential roles as cofactors in enzymatic reactions crucial to metabolism, energy production, DNA synthesis, and cellular maintenance. Unlike fat-soluble vitamins, water-soluble vitamins are not stored in significant quantities in the human body and must be obtained regularly from the diet. Most of them function as coenzymes or are converted into coenzyme forms that participate in biochemical pathways.

Overview

The water-soluble vitamins include:

• Vitamin B₁ (Thiamine)
• Vitamin B₂ (Riboflavin)
• Vitamin B₃ (Niacin)
• Vitamin B₅ (Pantothenic acid)
• Vitamin B₆ (Pyridoxine)
• Vitamin B₇ (Biotin)
• Vitamin B₉ (Folate)
• Vitamin B₁₂ (Cobalamin)
• Vitamin C (Ascorbic acid)

Each of these vitamins has a specific biochemical function and contributes to metabolic pathways primarily by acting as cofactors or coenzyme precursors.

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Vitamin B₁ (Thiamine)

Cofactor: Thiamine pyrophosphate (TPP)

Enzymes:

• Pyruvate dehydrogenase
• α-Ketoglutarate dehydrogenase
• Branched-chain α-ketoacid dehydrogenase
• Transketolase (in the pentose phosphate pathway)

Function: TPP serves as a coenzyme for decarboxylation of α-ketoacids and for transketolation reactions. It is vital in glucose metabolism and the Krebs cycle.

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Vitamin B₂ (Riboflavin)

Cofactors:

• Flavin mononucleotide (FMN)
• Flavin adenine dinucleotide (FAD)

Enzymes:

• Succinate dehydrogenase (Krebs cycle and ETC)
• Acyl-CoA dehydrogenase (β-oxidation)
• Glutathione reductase

Function: FMN and FAD act as redox cofactors involved in electron transfer reactions. They are central to oxidative phosphorylation and energy production.

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Vitamin B₃ (Niacin)

Cofactors:

• Nicotinamide adenine dinucleotide (NAD⁺)
• Nicotinamide adenine dinucleotide phosphate (NADP⁺)

Enzymes:

• Lactate dehydrogenase
• Isocitrate dehydrogenase
• Malate dehydrogenase

Function: NAD⁺ and NADP⁺ are essential electron carriers in catabolic and anabolic reactions, respectively. They are key to glycolysis, TCA cycle, and lipid synthesis.

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Vitamin B₅ (Pantothenic Acid)

Cofactor: Coenzyme A (CoA)

Function: CoA is involved in acyl-group transfer reactions. It plays a central role in fatty acid metabolism, the TCA cycle, and the synthesis of cholesterol, acetylcholine, and steroid hormones.

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Vitamin B₆ (Pyridoxine, Pyridoxal, Pyridoxamine)

Cofactor: Pyridoxal phosphate (PLP)

Enzymes:

• Aminotransferases (e.g., ALT, AST)
• Glycogen phosphorylase
• δ-Aminolevulinic acid synthase (heme synthesis)

Function: PLP is a versatile coenzyme in amino acid metabolism, including transamination, decarboxylation, and deamination reactions. It is also involved in neurotransmitter synthesis and heme biosynthesis.

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Vitamin B₇ (Biotin)

Cofactor: Biotin (prosthetic group)

Enzymes:

• Acetyl-CoA carboxylase (fatty acid synthesis)
• Pyruvate carboxylase (gluconeogenesis)
• Propionyl-CoA carboxylase (odd-chain fatty acid metabolism)

Function: Biotin acts as a CO₂ carrier in carboxylation reactions, crucial in fatty acid synthesis, gluconeogenesis, and amino acid metabolism.

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Vitamin B₉ (Folate)

Cofactor: Tetrahydrofolate (THF) and its derivatives

Enzymes:

• Thymidylate synthase
• Methionine synthase
• Purine synthase

Function: THF is essential for the transfer of one-carbon units in nucleotide biosynthesis and amino acid metabolism. Folate is vital for DNA synthesis and repair, making it crucial during cell division.

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Vitamin B₁₂ (Cobalamin)

Cofactors:

• Methylcobalamin
• Adenosylcobalamin

Enzymes:

• Methionine synthase (homocysteine methylation)
• Methylmalonyl-CoA mutase (fatty acid metabolism)

Function: B₁₂ is necessary for methyl group transfers and the metabolism of odd-chain fatty acids. It also maintains nerve cell health and supports DNA synthesis.

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Vitamin C (Ascorbic Acid)

Function:

• Cofactor for prolyl and lysyl hydroxylase (collagen synthesis)
• Antioxidant
• Enhances iron absorption
• Involved in norepinephrine synthesis from dopamine

Function: Ascorbic acid acts as a reducing agent and maintains the active forms of iron and copper in enzymes. It supports immune function and connective tissue integrity.

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Clinical Relevance

Deficiency in water-soluble vitamins can lead to:

• Vitamin B₁: Beriberi, Wernicke-Korsakoff syndrome
• Vitamin B₂: Cheilosis, glossitis, corneal vascularization
• Vitamin B₃: Pellagra (dermatitis, diarrhea, dementia)
• Vitamin B₅: Fatigue, paresthesia
• Vitamin B₆: Neuropathy, sideroblastic anemia
• Vitamin B₇: Dermatitis, alopecia, enteritis
• Vitamin B₉: Megaloblastic anemia, neural tube defects
• Vitamin B₁₂: Pernicious anemia, neuropathy
• Vitamin C: Scurvy (bleeding gums, poor wound healing)

References

1. Murray RK, Granner DK, Rodwell VW. Harper’s Illustrated Biochemistry. McGraw-Hill Education.
2. Nelson DL, Cox MM. Lehninger Principles of Biochemistry. W.H. Freeman.
3. Gropper SS, Smith JL. Advanced Nutrition and Human Metabolism.