51-35-4

Production Methods

In the past L-Hydroxyproline was isolated by hydrolysis of animal collagen, e. g. gelatine or collagen, of which it is a major constituent. L-Hydroxyproline is an unnatural amino acid which is made in the body by hydroxylation of L-Proline. The presence of L-Hydroxyproline and proline are key to maintaining the stability of the tight collagen helix. Today L-Hydroxyproline is manufactured by bio-catalysed hydroxylation of proline in bacteria. Together with its other isomers, L-Hydroxyproline is also used as an inter mediate for a range of pharmaceutical active ingredients. Produced by hydroxylation of L-proline after protein synthesis. It is contained rich in collagen and elastin. Known to stabilization of triple-helix structure of collagen. Widely used as an intermediate for medicines.

Biochem/physiol Actions

Trans-4-Hydroxy-L-proline is used in the organic synthesis of depsilairdin analogues, noncompetitive peptidomimetic inhibitors of multidrug resistance P-glycoprotein and 3-guaninyl-5-hydroxymethyl-2-pyrrolidinone (4) or 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone (5) nucleoside analogues.

Purification Methods

Crystallise it from MeOH/EtOH (1:1). Separation from normal allo-isomer can be achieved by crystallisation of the copper salts [see Levine Biochemical Preparations 8 114 1961]. Separation from proline is achieved via the crystalline picrate, CdCl2, or acid ammonium rhodanate salts [see Greenstein & Winitz The Chemistry of the Amino Acids J. Wiley, Vol 3 p 2182 1961, Kapfhammer & Mohn Z Physiol Chem 306 76 1956]. [Beilstein 22/5 V 7.]

Role in Collagen Synthesis

Hydroxyproline is a non-proteinogenic amino acid formed by the hydroxylation of proline. It plays a pivotal role in stabilizing the helical structure of collagen fibers, contributing to the structural integrity of connective tissues.

Role in Disease Pathophysiology

Abnormalities in hydroxyproline metabolism are implicated in various diseases, including graft versus host disease, keloids, and vitiligo. Elevated levels of hydroxyproline are observed in these disorders, while decreased levels indicate poor wound healing.

Significance in Liver Health

In liver fibrosis, hydroxyproline levels in tissues, serum, and urine serve as important indicators of fibrogenesis rates and disease progression. Its presence in the extracellular matrix (ECM) produced by hepatic stellate cells (HSCs) helps preserve liver cell integrity and function.

Diagnostic Marker

Hydroxyproline estimation is utilized as a marker for diagnosing liver fibrosis and evaluating the anti-fibrotic effects of therapeutic interventions, including herbal and non-herbal medicines. It serves as a noninvasive biomarker for detecting severe fibrosis in chronic liver diseases.

Biochemical Properties

Hydroxyproline, along with proline, constitutes about one-third of the amino acids in collagen synthesis.
The presence of 伪-amino groups in proline and hydroxyproline classifies them as 伪-amino acids. Hydroxyproline contributes to the stability of collagen proteins, essential for maintaining the structure and function of connective tissues.

Enzymatic Hydroxylation

Hydroxyproline formation involves the catalytic hydroxylation of proline units by proline hydroxylase enzyme, utilizing ascorbic acid and oxygen as cofactors.

Definition

ChEBI: An optically active form of 4-hydroxyproline having L-trans-configuration.

General Description

Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards