Basic Info

Common Name4-Hydroxyproline(F05370)
2D Structure
Description

4-Hydroxyproline (or hydroxyproline or Hyp) is a major component of the protein collagen. Hydroxyproline is produced by hydroxylation of the amino acid proline and is, therefore, a post-translationally modified amino acid. Hydroxyproline and proline play key roles for collagen stability. In particular, they permit the sharp twisting of the collagen helix. 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 in tissue or biological samples. Increased serum and urine levels of hydroxyproline have been found in Paget's disease Hydroxyproline (Hyp) content in biological fluids is used as a parameter of collagen catabolism, especially bone resorption or tissue degradation. Bedridden and elderly individuals show significantly elevated serum levels of hydroxyproline in comparison to normal, active individuals Elevated levels of urinary hydroxyproline are also indicative of muscle damage Increased reactive oxygen species (ROS) are also known to accelerate collagen degradation. Hydroxyproline levels increase in cases of depression and stress (A3486, A3487, A3488, A3489).

FRCD IDF05370
CAS Number51-35-4
PubChem CID5810
FormulaC5H9NO3
IUPAC Name

(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid

InChI Key

PMMYEEVYMWASQN-DMTCNVIQSA-N

InChI

InChI=1S/C5H9NO3/c7-3-1-4(5(8)9)6-2-3/h3-4,6-7H,1-2H2,(H,8,9)/t3-,4+/m1/s1

Canonical SMILES

C1C(CNC1C(=O)O)O

Isomeric SMILES

C1[C@H](CN[C@@H]1C(=O)O)O

Wikipedia4-Hydroxyproline
Synonyms
        
            trans-4-Hydroxy-L-proline
        
            51-35-4
        
            hydroxyproline
        
            L-Hydroxyproline
        
            (2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acid
        
            L-4-hydroxyproline
        
            trans-4-Hydroxyproline
        
            hydroxy-L-proline
        
            4-Hydroxy-L-proline
        
            H-Hyp-OH
        
Classifies
                

                  
                    Animal Toxin
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
SubclassAmino acids, peptides, and analogues
Intermediate Tree NodesAmino acids and derivatives - Alpha amino acids and derivatives
Direct ParentProline and derivatives
Alternative Parents
Molecular FrameworkAliphatic heteromonocyclic compounds
SubstituentsProline or derivatives - Alpha-amino acid - L-alpha-amino acid - Pyrrolidine carboxylic acid - Pyrrolidine carboxylic acid or derivatives - Pyrrolidine - 1,2-aminoalcohol - Amino acid - Secondary alcohol - Carboxylic acid - Secondary aliphatic amine - Monocarboxylic acid or derivatives - Azacycle - Secondary amine - Organoheterocyclic compound - Organooxygen compound - Organonitrogen compound - Alcohol - Organic nitrogen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organic oxygen compound - Amine - Carbonyl group - Aliphatic heteromonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as proline and derivatives. These are compounds containing proline or a derivative thereof resulting from reaction of proline at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.

Properties

Property NameProperty Value
Molecular Weight131.131
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count4
Rotatable Bond Count1
Complexity125
Monoisotopic Mass131.058
Exact Mass131.058
XLogP-3.3
Formal Charge0
Heavy Atom Count9
Defined Atom Stereocenter Count2
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.6522
Human Intestinal AbsorptionHIA+0.9652
Caco-2 PermeabilityCaco2-0.7144
P-glycoprotein SubstrateNon-substrate0.5460
P-glycoprotein InhibitorNon-inhibitor0.9789
Non-inhibitor0.9870
Renal Organic Cation TransporterNon-inhibitor0.8560
Distribution
Subcellular localizationMitochondria0.5864
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8242
CYP450 2D6 SubstrateNon-substrate0.7501
CYP450 3A4 SubstrateNon-substrate0.6878
CYP450 1A2 InhibitorNon-inhibitor0.9332
CYP450 2C9 InhibitorNon-inhibitor0.9619
CYP450 2D6 InhibitorNon-inhibitor0.9367
CYP450 2C19 InhibitorNon-inhibitor0.9623
CYP450 3A4 InhibitorNon-inhibitor1.0000
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9913
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9682
Non-inhibitor0.9178
AMES ToxicityNon AMES toxic0.9149
CarcinogensNon-carcinogens0.9640
Fish ToxicityLow FHMT0.9000
Tetrahymena Pyriformis ToxicityLow TPT0.9720
Honey Bee ToxicityLow HBT0.5710
BiodegradationReady biodegradable0.9178
Acute Oral ToxicityIII0.5577
Carcinogenicity (Three-class)Non-required0.7268

Model Value Unit
Absorption
Aqueous solubility-0.3499LogS
Caco-2 Permeability0.1806LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.1441LD50, mol/kg
Fish Toxicity3.0514pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.9563pIGC50, ug/L

Targets

General Function:
L-proline transmembrane transporter activity
Specific Function:
Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recognize their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid (By similarity).
Gene Name:
SLC36A1
Uniprot ID:
Q7Z2H8
Molecular Weight:
53075.045 Da
References
  1. Thondorf I, Voigt V, Schafer S, Gebauer S, Zebisch K, Laug L, Brandsch M: Three-dimensional quantitative structure-activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1). Bioorg Med Chem. 2011 Nov 1;19(21):6409-18. doi: 10.1016/j.bmc.2011.08.058. Epub 2011 Sep 5. [21955456 ]