The Hydroxyproline to Proline Ratio describes the relationship between Proline and Hydroxyproline and can be looked at in relation to your collagen metabolism.
What is Hydroxyproline?
Hydroxyproline is a collagen related amino acid. Hydroxyproline is a nonessential amino acid, which means that it is manufactured from other amino acids in the liver. Hydroxyproline is necessary for the construction of the body’s major structural protein, collagen. Hydroxyproline is present in essentially all tissues and all genetic types of collagen.
Defects in collagen synthesis lead to easy bruising, internal bleeding, breakdown of connective tissue of the ligaments and tendons, and increased risk to blood vessel damage.
Hydroxyproline’s immediate precursor is proline. The conversion of proline to hydroxyproline requires vitamin C (ascorbic acid). Vitamin C deficiency results in the poor conversion of proline to hydroxyproline.
High levels of Hydroxyproline:
– Collagen synthesis requires iron, alpha-ketoglutarate and vitamin C. Chondroitin sulfate and manganese can also be helpful.
– Elevated urinary hydroxyproline is a reflection of bone lysis and may also occur in RA, hyperparathyroidism, and OM; 
– Increased serum and urine levels of hydroxyproline have been demonstrated in Paget’s disease 
What is Proline?
Proline is a nonessential amino acid, which means that it is manufactured from other amino acids in the liver; it does not have to be obtained directly through the diet.
Proline is the precursor to hydroxyproline, which is a major amino acid found in the connective tissue of the body – collagen.
– Its effect in human nutrition, other than as a source of nitrogen, is not well established.
– Supplementation with proline has not been found to increase collagen formation.
– Proline is found in virtually every dietary protein except lactalbumin. Although proline is not classified as an essential amino acid, proline levels in plasma are dramatically reduced with a proline-free diet.
– Proline is a major constituent of collagen and can be metabolized to alpha-KG, which is important in ammonia detoxification and the citric acid cycle.-
– Hyperprolinemia is a recognized genetic disorder characterized by renal and central nervous system dysfunction.
– Vitamin C and iron are known cofactors in the conversion to hydroxyproline and may be useful if connective tissue symptoms are present. Acute or chronic deficiency of vitamin C produces a significant increase in the proline/hydroxyproline ration in urine.
High levels of Proline:
– Proline is universally required to protein synthesis and is metabolized to hydroxyproline, an important component in connective tissue. Therefore, high levels may reflect inadequate connective tissue synthesis. Proline can also be oxidized to glutamic acid, requiring niacin as a cofactor precursor.
– Higher levels of proline can demonstrate poor utilization. Add vitamin C to aid collagen synthesis if symptoms present. Niacin (cofactor precursor) helps oxidize proline to glutamate.
– High levels of proline and hydroxyproline may be lowered by supplementing vitamin C and Iron.
– Consistently high levels of proline can potentially be due to a genetic condition called Hyperprolinemia. Levels of blood proline levels can be 3 to 15 times higher than normal levels. [L]
Low levels of Proline:
– Low plasma levels of proline reflect low tissue supply of this amino acid. As proline is a major component of collagen, low plasma level can mean defective connective tissue synthesis. Alpha-KG could be used to normalize the value.
– Low proline levels can indicate a low protein diet and may prevent optimal connective tissue maintenance.
Lower values of the Hydroxyproline/Proline Ratio:
Vitamin C deficiency decreases the conversion of proline to hydroxyproline, which leads to reduced collagen stability. In this case your proline is relatively high compared to your hydroxyproline
Higher values of the Hydroxyproline/Proline Ratio:
Increased hydroxyproline levels in the urine and/or serum are normally associated with degradation of connective tissue.
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