What Enzyme is a Vitamin C Cofactor For?

December 14, 2025 •

3 min read

Vitamin C, also known as ascorbic acid, is an essential cofactor for at least eight different enzymes in the human body. While its antioxidant role is well-known, its critical function as a reducing agent for enzymatic reactions often goes unnoticed. This vital nutrient facilitates key biochemical processes, from creating strong connective tissue to synthesizing important neurotransmitters and hormones.

Quick Summary

Vitamin C is an essential cofactor for several enzymes, most notably the hydroxylases required for building stable collagen, synthesizing carnitine, and producing neurotransmitters like norepinephrine. Its role is to keep the necessary metal ions, typically iron or copper, in their active, reduced state. A deficiency impacts these enzymatic processes, leading to serious health issues.

Key Points

Collagen Synthesis: Vitamin C is a critical cofactor for prolyl and lysyl hydroxylase enzymes, which are necessary for strengthening collagen's triple-helix structure.
Scurvy Explained: The symptoms of scurvy, such as bleeding gums and poor wound healing, are directly caused by a lack of vitamin C, leading to defective collagen synthesis.
Carnitine Production: Vitamin C is a required cofactor for two hydroxylases involved in synthesizing carnitine, a molecule vital for transporting fatty acids for energy.
Neurotransmitter Creation: Dopamine β-hydroxylase, the enzyme that converts dopamine to norepinephrine, needs vitamin C to maintain its copper-dependent active site.
Epigenetic Regulation: Recent research has shown vitamin C's importance as a cofactor for TET and Jumonji enzymes, which play roles in DNA and histone demethylation, influencing gene expression.
Redox Function: The underlying mechanism for all these roles is vitamin C's ability to act as a reducing agent, keeping metal ions ($Fe^{2+}$ or $Cu^{+}$) in their reduced, functional state within enzymes.
Iron Absorption: In addition to its enzymatic roles, vitamin C also enhances the absorption of non-heme iron by keeping it in its reduced ($Fe^{2+}$) state.

The Core Function of Vitamin C as an Enzyme Cofactor

At the molecular level, vitamin C acts as a potent reducing agent, donating electrons to other molecules. For the enzymes that require it as a cofactor, this reducing power is used to regenerate the enzyme's active site. Many of these enzymes are hydroxylases that rely on a metal ion, such as iron ($Fe^{2+}$) or copper ($Cu^{+}$), for their catalytic activity. During the enzymatic reaction, this metal ion can become oxidized, rendering the enzyme inactive. Vitamin C steps in to reduce the metal ion back to its active state, allowing the enzymatic process to continue efficiently. This vital action explains why a severe deficiency, like scurvy, results in the widespread systemic problems associated with dysfunctional connective tissues and metabolism.

Key Enzymes Requiring Vitamin C

Enzymes for Collagen Synthesis

Perhaps the most famous role of vitamin C is its necessity for producing healthy, robust collagen, the most abundant protein in the body. This process involves a group of enzymes called hydroxylases, which perform a post-translational modification on the amino acids proline and lysine within the collagen polypeptide chains. Prolyl and lysyl hydroxylases are key enzymes that require vitamin C as a cofactor. Prolyl hydroxylase is crucial for forming the stable triple-helical structure of collagen, while lysyl hydroxylase is essential for cross-linking collagen fibers, providing strength and stability to connective tissues. A lack of vitamin C results in weak, unstable collagen, characteristic of scurvy.

Enzymes for Carnitine Synthesis

Carnitine is a molecule essential for transporting long-chain fatty acids into the mitochondria for energy production. Its synthesis pathway involves two vitamin C-dependent enzymes: ε-N-trimethyl-L-lysine hydroxylase (TMLD) and γ-butyrobetaine hydroxylase (γ-BBD). TMLD catalyzes the initial hydroxylation step, and γ-BBD performs the final conversion to L-carnitine. Vitamin C deficiency can therefore impact energy metabolism.

Enzymes for Neurotransmitter and Hormone Synthesis

Vitamin C is vital for the synthesis of important neurotransmitters and peptide hormones. Dopamine β-hydroxylase, an enzyme that converts dopamine to norepinephrine, requires vitamin C to maintain its copper cofactor in a reduced state. Another enzyme, peptidylglycine α-amidating monooxygenase (PAM), involved in the amidation of peptide hormones like vasopressin and oxytocin, also depends on vitamin C. These roles highlight vitamin C's importance for nervous system and endocrine health.

Enzymes for Gene Regulation

Vitamin C acts as a cofactor for epigenetic enzymes, including the ten-eleven translocation (TET) enzymes and Jumonji domain-containing histone demethylases. These enzymes influence DNA and histone demethylation, impacting gene expression and cellular health.

Comparison of Vitamin C-Dependent Enzymes


Enzyme Group	Key Enzymes	Biological Function	Cofactor's Role	Impact of Deficiency
Collagen Biosynthesis	Prolyl and Lysyl Hydroxylases	Stabilizes collagen's triple-helix structure for connective tissue strength.	Reduces iron ($Fe^{3+}$ back to $Fe^{2+}$) to maintain enzyme activity.	Weak collagen, fragile blood vessels, poor wound healing (Scurvy).
Carnitine Biosynthesis	ε-N-trimethyl-L-lysine and γ-butyrobetaine hydroxylases	Synthesizes carnitine for fatty acid transport and energy production.	Aids in hydroxylation reactions that enable the synthesis pathway.	Impaired fatty acid metabolism, reduced energy production, lethargy.
Neurotransmitter Synthesis	Dopamine β-hydroxylase, PAM	Converts dopamine to norepinephrine; amidates peptide hormones.	Maintains copper ions ($Cu^{2+}$ back to $Cu^{+}$) at the enzyme's active site.	Potential impact on nervous system function and stress response.
Gene Regulation	TET enzymes, Jumonji demethylases	Influences epigenetic pathways through DNA and histone demethylation.	Enables the hydroxylation and demethylation processes of these dioxygenases.	Potential for aberrant gene expression patterns and altered cell fate.

Conclusion

Vitamin C's role as a cofactor is critical for numerous enzymatic processes essential for human health. It supports collagen synthesis for strong connective tissues, carnitine production for energy, neurotransmitter synthesis for nervous system function, and epigenetic modifications that regulate gene expression. Its reducing ability keeps metal-dependent enzymes active. Adequate vitamin C intake is therefore necessary to prevent deficiencies like scurvy and ensure these vital pathways function correctly.

Frequently Asked Questions

The primary enzyme family that uses vitamin C as a cofactor is the hydroxylases, which are involved in hydroxylation reactions. These enzymes are crucial for synthesizing collagen, carnitine, and certain neurotransmitters.

Prolyl hydroxylase, which is vital for collagen synthesis, relies on a reduced iron ion ($Fe^{2+}$) to function. Vitamin C reduces any oxidized iron ($Fe^{3+}$) back to its active $Fe^{2+}$ form, allowing the enzyme to continue hydroxylating proline residues effectively.

Yes, vitamin C is a cofactor for dopamine β-hydroxylase, the enzyme that converts dopamine to norepinephrine. This is essential for proper nervous system and endocrine function.

Vitamin C is a necessary cofactor for two enzymes involved in the synthesis of carnitine, a molecule that helps transport fatty acids into mitochondria for energy generation. Without sufficient vitamin C, carnitine production is hindered.

Yes, low vitamin C levels can impair wound healing significantly. This is because the synthesis of stable, strong collagen is dependent on vitamin C, and collagen is a primary component of scar tissue and connective tissue repair.

Yes, vitamin C acts as a cofactor for epigenetic enzymes, including the TET dioxygenases and Jumonji demethylases. These enzymes play roles in DNA and histone demethylation, thereby regulating gene expression.

If there is insufficient vitamin C, the metal ion (usually iron or copper) at the enzyme's active site remains in its oxidized state. The enzyme becomes inactive until vitamin C or another reductant can regenerate it.