Quick Search
CAS Number: 51-35-4
IUPAC name: (2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acid
APPLICATIONS
Trans-4-hydroxy-L-proline is an optically active form of 4-hydroxyproline having L-trans-configuration.
Hydroxyproline has a role as a human metabolite, a plant metabolite and a mouse metabolite.
Hydroxyproline is a tautomer of a trans-4-hydroxy-L-proline zwitterion.
Hydroxyproline is a neutral heterocyclic protein amino acid.
Hydroxyproline is found in collagen and as such it is common in many gelatin products.
Hydroxyproline is mostly used as a diagnostic marker of bone turnover and liver fibrosis.
Therapeutically, hydroxyproline is being studied as an an experimental medicine but is approved in France as a combination topical gel product called Cicactive for small, superficial wounds.
Hydroxyproline as well as proline and glycine are the major components of collagen.
Collagen is on one of the main building blocks of connective tissue such as skin, bone, and cartilage.
Thus when these tissues are damaged, hydroxyproline is necessary for repair of the damaged area.
Hydroxyproline is the traditional marker of bone resorption.
Hydroxyproline is a product of posttranslational hydroxylation of proline in the procollagen chain, which is released when type I collagen is degraded.
Hydroxyproline is a neutral heterocyclic protein amino acid.
Hydroxyproline is found in collagen and as such it is common in many gelatin products.
Hydroxyproline is mostly used as a diagnostic marker of bone turnover and liver fibrosis.
Therapeutically, hydroxyproline is being studied as an an experimental medicine but is approved in France as a combination topical gel product called Cicactive for small, superficial wounds.
Hydroxyproline is a major component of the protein collagen.
Hydroxyproline and proline play key roles for collagen stability.
They permit the sharp twisting of the collagen helix.
Hydroxyproline helps provide stability to the triple-helical structure of collagen by forming hydrogen bonds.
Hydroxyproline is found in few proteins other than collagen.
The only other mammalian protein which includes hydroxyproline is elastin.
For this reason, hydroxyproline content has been used as an indicator to determine collagen and/or gelatin amount.
Hydroxyproline is used as a Pharmaceutical Intermediate.
Mostly Hydroxyproline is used in Cosmetics.
Hydroxyproline is used as Dietary Supplement.
Hydroxyproline is used as an indicator in determination of the amount of collagen presence in mixture, additive to improve taste quality of the fruit juice, soft drinks and other flavored liquids.
Further, hydroxyproline is used in incense sticks for the sweet smell purposes, and used in personal care products, such as hair and nails conditioner owing to its benefit – to increases the moisture retention of hairs and nails.
DESCRIPTION
In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelatin.
In 1905, Hermann Leuchs synthesized a racemic mixture of 4-hydroxyproline.
Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the gamma carbon atom.
Hydroxyproline is a major component of fibrillar collagen of all types, comprising ~14% of the total amino and imino acid content.
Hydroxyproline is produced by the post-translational modification of proline by the enzyme 4-prolyl hydroxylase.
In plasma, hydroxyproline exists in protein-bound, peptide-bound and free forms.
Most hydroxyproline is oxidized in the liver but a small proportion (~10%) is excreted in the urine.
Approximately 90% of collagen-derived hydroxyproline excretion is in the form of peptides resulting from collagen degradation, with the remainder in the form of fragments of the N- and C-terminal procollagen peptides cleaved during collagen synthesis.
When bone resorption is increased, urinary hydroxyproline excretion rises, because of the increased rate of catabolism of type 1 bone collagen.
Hydroxyproline, possibly one of the longest-established markers of bone resorption, is a product of the degradation of the helical region of type I collagen.
Hydroxyproline represents about 13% of the amino acid content of collagen and is released into the circulation during bone resorption but is not reincorporated into new collagen.
Hydroxyproline, an amino acid formed upon hydrolysis of connective-tissue proteins such as collagen (about 14 percent by weight) and elastin but rarely from other proteins.
First isolated (1902) from gelatin, a breakdown product of collagen, hydroxyproline is one of several so-called nonessential amino acids; i.e., animals can synthesize it from glutamic acid and do not require dietary sources.
Excretion of abnormal quantities of hydroxyproline is a symptom of the connective-tissue disease called Marfan syndrome.
Hydroxyproline is a non-proteinogenic amino acid, that has a molecular weight of 131.13 g/mol and is synthesized by post-translational hydroxylation of proline during collagen biosynthesis.
Investigations of physiological and pathological collagen metabolism most commonly utilize measurements of hydroxyproline in the plasma, urine and body tissue. Therefore, determination of hydroxyproline provides useful information for the diagnosis and prognosis of diseases caused by disorders of the collagen metabolism.
Such conditions include hyperthyroidism, hyperparathyroidism, acromegaly, Paget’s disease, osteomalacia, rickets, Marfan syndrome, osteogenesis imperfecta, sclerodactyly, dermatomyositis and Cushing syndrome.
Proline is not common in helical structures.
However, 13.5% of mammalian collagen is composed of hydroxyproline, a modified amino acid containing a hydroxy group on the R group.
Knowing that collagen is a major structural protein, explain how in this case the structure of hydroxyproline matches its function.
Hydroxyproline is a neutral heterocyclic protein amino acid.
Hydroxyproline is found in collagen and as such it is common in many gelatin products.
Hydroxyproline is mostly used as a diagnostic marker of bone turnover and liver fibrosis.
Therapeutically, hydroxyproline is being studied as an an experimental medicine but is approved in France as a combination topical gel product called Cicactive for small, superficial wounds.
Hydroxyproline is a structurally and physiologically important imino acid in animals.
Hydroxyproline is provided from diets and endogenous synthesis, and its conversion into glycine enhances the production of glutathione, DNA, heme, and protein.
Furthermore, oxidation of hydroxyproline by hydroxyproline oxidase (OH-POX) plays an important role in cell antioxidative reactions, survival, and homeostasis. Understanding the mechanisms whereby hydroxyproline participates in metabolism and cell signaling can improve the nutrition and health of animals and humans.
Hydroxyproline is produced by hydroxylation of the amino acid proline by the enzyme prolyl hydroxylase following protein synthesis (as a post-translational modification).
The enzyme catalyzed reaction takes place in the lumen of the endoplasmic reticulum.
Although it is not directly incorporated into proteins, hydroxyproline comprises roughly 4% of all amino acids found in animal tissue, an amount greater than seven other amino acids that are translationally incorporated.
PRODUCTION AND FUNCTION
Hydroxyproline is produced by hydroxylation of the amino acid proline by the enzyme prolyl hydroxylase following protein synthesis (as a post-translational modification).
The enzyme catalyzed reaction takes place in the lumen of the endoplasmic reticulum.
Although it is not directly incorporated into proteins, hydroxyproline comprises roughly 4% of all amino acids found in animal tissue, an amount greater than seven other amino acids that are translationally incorporated.
Animals
-Collagen
Hydroxyproline is a major component of the protein collagen, comprising roughly 13.5% of mammalian collagen.
Hydroxyproline and proline play key roles for collagen stability.
They permit the sharp twisting of the collagen helix.
In the canonical collagen Xaa-Yaa-Gly triad (where Xaa and Yaa are any amino acid), a proline occupying the Yaa position is hydroxylated to give a Xaa-Hyp-Gly sequence.
This modification of the proline residue increases the stability of the collagen triple helix.
Hydroxyproline was initially proposed that the stabilization was due to water molecules forming a hydrogen bonding network linking the prolyl hydroxyl groups and the main-chain carbonyl groups.
Hydroxyproline was subsequently shown that the increase in stability is primarily through stereoelectronic effects and that hydration of the hydroxyproline residues provides little or no additional stability.
-Non-collagen
In addition to collagen, the mammalian proteins elastin and argonaute 2 have collagen-like domains in which hydroxyproline is formed.
Some snail poisons, conotoxins, contain hydroxyproline, but lack collagen-like sequences.
Hydroxylation of proline has been shown to be involved in targeting Hypoxia-inducible factor (HIF) alpha subunit (HIF-1 alpha) for degradation by proteolysis.
Under normoxia (normal oxygen conditions) EGLN1 protein hydroxylates the proline at the 564 position of HIF-1 alpha, which allows ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) and subsequent targeting for proteasome degradation.
Hydroxyproline is found in few proteins other than collagen.
For this reason, hydroxyproline content has been used as an indicator to determine collagen and/or gelatin amount.
Plants
Hydroxyproline rich glycoproteins (HRGPs) are also found in plant cell walls.
These hydroxyprolines serve as the attachment points for glycan chains which are added as post-translational modifications.
CLINICAL SIGNIFICANCE
Proline hydroxylation requires ascorbic acid (vitamin C).
The most obvious, first effects (gingival and hair problems) of absence of ascorbic acid in humans come from the resulting defect in hydroxylation of proline residues of collagen, with reduced stability of the collagen molecule, causing scurvy.
Increased serum and urine levels of hydroxyproline have also been demonstrated in Paget's disease.
OTHER HYDROXYPROLINES
Other hydroxyprolines also exist in nature.
The most notable ones are 2,3-cis-, 3,4-trans-, and 3,4-dihydroxyproline, which occurs in diatom cell walls and are postulated to have a role in silica deposition. Hydroxyproline is also found in the walls of oomycetes, fungus-like protists related to diatoms.
(2S,4S)-cis-4-Hydroxyproline is found in the toxic cyclic peptides from Amanita mushrooms (e.g., phalloidin).
SYNONYMS
(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid
N-methyl-trans-4-hydroxy-L-proline
NMH-Pro
trans-4-hydroxy-L-proline
trans-L-Hydroxyproline
trans-4-Hydroxy-L-proline
Hydroxyproline
