In addition to its antioxidant function, vitamin C is also a cofactor for a number of enzymes. The enzymes proline hydroxylase and lysyl hydroxylase are important in the formation of the protein collagen. Hydroxylase means that the enzymes add alcohol (hydroxyl, -OH) to the amino acids proline and lysine, as shown below.

Figure 9.321 Proline hydroxylase adds an alcohol group (circled) to proline forming hydroxyproline1,2

Figure 9.322 Lysyl hydroxylase adds an alcohol group (circled) to lysine forming hydroxylysine3,4

As shown below, proline and lysyl hydroxylases require ferrous iron (Fe2+) to function. But in the course of the hydroxylating proline or lysine, ferrous iron (Fe2+) is oxidized to ferric iron (Fe3+). Ascorbic acid is required to reduce Fe3+ to Fe2+, forming semidehydroascorbic acid in the process. With Fe2+, the enzyme is then able to continue to hydroxylate proline and lysine.

Figure 9.323 Ascorbic acid reduces iron so that it can continue to serve as a cofactor for proline and lysyl hydroxylases

Why should you care about collagen formation? Because collagen is estimated to account for 30% or more of total body proteins⁵. Collagen contains a number of hydroxylated prolines and lysines that are needed for collagen strands to properly cross-link. This cross-linking is important for collagen to wind together like a rope, forming the strong triple helix known as tropocollagen. This process is shown in the following animation, as well as in the figure below.

Figure 9.324 Production of cross-linked tropocollagen in the presence of adequate vitamin C

But if there isn’t enough ascorbic acid available, the collagen strands are underhydroxylated and instead of forming strong tropocollagen, the underhydroxylated collagen is degraded as shown below.

Figure 9.325 Production of underhydroxylated collagen

This weak collagen then results in the symptoms seen in the vitamin C deficiency, scurvy, that will be discussed in the next subsection.

Ascorbic Acid is also needed for:

Carnitine synthesis

Tyrosine synthesis and catabolism

Serotonin (neurotransmitter) synthesis

Other hormone and neurotransmitter synthesis⁶

The figure below shows how ascorbic acid is needed for dopamine hydroxylase, which ultimately produces the hormone epinephrine.

Figure 9.326 Dopamine beta-hydroxylase requires ascorbic acid to produce norepinephrine

References & Links

1. https://en.wikipedia.org/wiki/Proline#/media/File:Prolin_-_Proline.svg

2. http://en.wikipedia.org/wiki/File:Hydroxyproline_structure.svg

3. https://en.wikipedia.org/wiki/Lysine#/media/File:L-lysine-monocation-2D-skeletal.png

4. http://en.wikipedia.org/wiki/File:Hydroxylysine.png

5. Di Lullo G, Sweeney S, Korkko J, Ala-Kokko L, San Antonio J. (2002) Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. The Journal of Biological Chemistry 277(6): 4223-4231.

6. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

7. http://en.wikipedia.org/wiki/File:Catecholamines_biosynthesis.svg