Hydroxyproline is a non-essential amino acid, a modified version of proline. While not used to build proteins directly, it is one of the most abundant amino acids in the body due to its role in collagen. As the primary structural protein in connective tissues, collagen makes hydroxyproline a component of skin, bones, tendons, and cartilage. This contributes significantly to the body’s structural framework.
The Role of Hydroxyproline in Collagen
Collagen is composed of three separate polypeptide chains that twist around each other to form a right-handed triple helix. This structure resembles a three-stranded rope, providing significant resilience. The integrity of this entire rope-like structure depends heavily on the presence of hydroxyproline.
The stability of the collagen triple helix is increased by the properties of hydroxyproline. After the initial assembly of collagen chains, specific proline amino acids are converted into hydroxyproline. The hydroxyl (-OH) group added in this process locks the individual chains into the tight helical conformation through hydrogen bonds. This chemical bracing prevents the triple helix from unwinding under stress.
This molecular stability translates to the functional properties of connective tissues. In the skin, this strength helps maintain elasticity and firmness, while in bones, it contributes to a robust matrix that withstands mechanical force. For cartilage and tendons, this stability allows joints to move smoothly and muscles to transmit force without the tissues tearing.
How the Body Creates Hydroxyproline
Hydroxyproline is not obtained from the diet and inserted into growing protein chains like standard amino acids are. Instead, the body manufactures it through post-translational modification. This means the modification happens after the initial protein chain has been synthesized, starting with a chain of amino acids, including regular proline, assembled in the cell.
Following this synthesis, the enzyme prolyl hydroxylase acts on the proline residues within the new collagen chain. This reaction, occurring in the endoplasmic reticulum, attaches a hydroxyl group to proline, converting it into hydroxyproline. This conversion allows the collagen to mature into its final, stable form.
The function of prolyl hydroxylase is dependent on Vitamin C (ascorbic acid), which acts as a cofactor for the enzyme. Without sufficient Vitamin C, this hydroxylation process fails, and the resulting collagen is weak and unstable. The disease scurvy is a direct consequence of this failure, as a lack of Vitamin C inhibits hydroxyproline synthesis. This leads to compromised blood vessels, bleeding gums, and poor wound healing.
Dietary Sources and Supplements
While the body synthesizes its own hydroxyproline, the building blocks for collagen can be supported through diet. Foods rich in collagen are direct sources of hydroxyproline and its precursor, proline. Bone broth, made by simmering animal bones, is a well-known source, as are gelatin and the skin of fish and poultry.
Collagen supplements are a direct way to ingest these components and contain hydrolyzed collagen, also known as collagen peptides. This means the collagen is broken down into smaller, more easily absorbed chains of amino acids. These supplements provide the body with a supply of glycine, proline, and hydroxyproline for its own collagen production.
Consuming collagen from food or supplements does not guarantee it will be used to build collagen in a specific area like the skin or joints. The body breaks down ingested collagen into its constituent amino acids and distributes them where they are needed. However, these sources provide the specific amino acids required for the body to build and maintain its own collagen.
Hydroxyproline as a Medical Marker
Tissue breakdown and remodeling are constant processes, and hydroxyproline serves as a useful biomarker for these activities. When collagen is degraded, hydroxyproline is released into the bloodstream and excreted in the urine. Measuring hydroxyproline levels in urine gives clinicians an indication of the rate of collagen turnover, particularly bone resorption.
This measurement has been used to monitor medical conditions with high rates of bone turnover. For example, in Paget’s disease of bone, which involves abnormal bone destruction and regrowth, urinary hydroxyproline levels can be elevated. It has also been used to assess bone resorption in osteoporosis and monitor the effectiveness of treatments.
While urinary hydroxyproline was an early marker for bone resorption, its use has become less common. Its levels can be influenced by diet, and it is present in all types of collagen, not just bone. Newer biomarkers specific to the breakdown of type I collagen from bone have since been developed and are often preferred for their greater specificity.