L-HYDROXYPROLINE

General Information

Mainterm	L-HYDROXYPROLINE
Doc Type	NUL
CAS Reg.No.(or other ID)	51-35-4
Regnum

From www.fda.gov

Computed Descriptors

Download SDF

2D Structure
CID	5810
IUPAC Name	(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid
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
InChI Key	PMMYEEVYMWASQN-DMTCNVIQSA-N
Canonical SMILES	C1C(CNC1C(=O)O)O
Molecular Formula	C5H9NO3
Wikipedia	4-hydroxyproline

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	131.131
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Complexity	125.0
CACTVS Substructure Key Fingerprint	A A A D c c B i M A A A A A A A A A A A A A A A A A A A A W A A A A A A A A A A A A A A A A A A A A A A H g A Q C A A A C D z h g A Y A C A L A A g A I A A C Q C A A A A A A A A A A A A I G I A A A C E B I A g C A E Q A A G E A C Q A A D a E Q A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area	69.6
Monoisotopic Mass	131.058
Exact Mass	131.058
XLogP3	None
XLogP3-AA	-3.3
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	9
Defined Atom Stereocenter Count	2
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

Food Additives Biosynthesis/Degradation

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.6522
Human Intestinal Absorption	HIA+	0.9652
Caco-2 Permeability	Caco2-	0.7144
P-glycoprotein Substrate	Non-substrate	0.5460
P-glycoprotein Inhibitor	Non-inhibitor	0.9789
P-glycoprotein Inhibitor	Non-inhibitor	0.9870
Renal Organic Cation Transporter	Non-inhibitor	0.8560
Distribution
Subcellular localization	Mitochondria	0.5864
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8242
CYP450 2D6 Substrate	Non-substrate	0.7501
CYP450 3A4 Substrate	Non-substrate	0.6878
CYP450 1A2 Inhibitor	Non-inhibitor	0.9332
CYP450 2C9 Inhibitor	Non-inhibitor	0.9619
CYP450 2D6 Inhibitor	Non-inhibitor	0.9367
CYP450 2C19 Inhibitor	Non-inhibitor	0.9623
CYP450 3A4 Inhibitor	Non-inhibitor	1.0000
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.9913
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9682
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9178
AMES Toxicity	Non AMES toxic	0.9149
Carcinogens	Non-carcinogens	0.9640
Fish Toxicity	Low FHMT	0.9000
Tetrahymena Pyriformis Toxicity	Low TPT	0.9720
Honey Bee Toxicity	Low HBT	0.5710
Biodegradation	Ready biodegradable	0.9178
Acute Oral Toxicity	III	0.5577
Carcinogenicity (Three-class)	Non-required	0.7268

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-0.3499	LogS
Caco-2 Permeability	0.1806	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.1441	LD50, mol/kg
Fish Toxicity	3.0514	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	-0.9563	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	None
Mechanism of Toxicity	None
Metabolism	None
Toxicity Values	None
Lethal Dose	None
Carcinogenicity (IARC Classification)	No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level	None
Health Effects	None
Treatment	None
Reference	Kelleher PC: Urinary excretion of hydroxyproline, hydroxylysine and hydroxylysine glycosides by patients with Paget's disease of bone and carcinoma with metastases in bone. Clin Chim Acta. 1979 Mar 15;92(3):373-9.[436278 ] Koike K, Li Y, Seo M, Sakurada I, Tezuka K, Uchikura K: Free 4-hydroxyproline content in serum of bedridden aged people is elevated due to fracture. Biol Pharm Bull. 2000 Jan;23(1):101-3.[10706420 ] Nogueira Ade C, Vale RG, Gomes AL, Dantas EH: The effect of muscle actions on the level of connective tissue damage. Res Sports Med. 2011 Oct;19(4):259-70. doi: 10.1080/15438627.2011.608046.[21988268 ] Lee KW, Kim SJ, Park JB, Lee KJ: Relationship between depression anxiety stress scale (DASS) and urinary hydroxyproline and proline concentrations in hospital workers. J Prev Med Public Health. 2011 Jan;44(1):9-13. doi: 10.3961/jpmph.2011.44.1.9.[21483218 ] Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762.[19212411 ] Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6.[12297216 ] Matsuda Y, Matsumoto K, Yamada A, Ichida T, Asakura H, Komoriya Y, Nishiyama E, Nakamura T: Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis. Hepatology. 1997 Jul;26(1):81-9.[9214455 ] Seibel MJ, Woitge HW: Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects. J Clin Densitom. 1999 Fall;2(3):299-321.[10548826 ] Akalin FA, Sengun D, Eratalay K, Renda N, Caglayan G: Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in patients with juvenile, rapidly progressive, and adult periodontitis. J Periodontol. 1993 May;64(5):323-9.[8515361 ] Akalin FA, Sengun D, Renda N, Eratalay K, Caglayan G: Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in periodontally healthy human subjects. J Nihon Univ Sch Dent. 1992 Sep;34(3):172-7.[1287145 ] Lee HS, Shun CT, Chiou LL, Chen CH, Huang GT, Sheu JC: Hydroxyproline content of needle biopsies as an objective measure of liver fibrosis: Emphasis on sampling variability. J Gastroenterol Hepatol. 2005 Jul;20(7):1109-14.[15955222 ] Akalin FA, Bozkurt FY, Sengun D, Renda N, Kalfa Z, Eratalay K, Velidedeoglu E: Hydroxyproline and total protein levels in gingiva from patients treated with phenytoin and cyclosporine-A. J Nihon Univ Sch Dent. 1996 Mar;38(1):21-30.[8648408 ] Diaz S, Reyes MV, Zepeda A, Gonzalez GB, Lopez JM, Campino C, Croxatto HB: Norplant((R)) implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. Hum Reprod. 1999 Oct;14(10):2499-505.[10527977 ] Fiorucci S, Rizzo G, Antonelli E, Renga B, Mencarelli A, Riccardi L, Morelli A, Pruzanski M, Pellicciari R: Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis. J Pharmacol Exp Ther. 2005 Oct;315(1):58-68. Epub 2005 Jun 24.[15980055 ] Kondo A, Ishikawa O, Okada K, Miyachi Y, Abe S, Kuboki Y: Measurement of histidinohydroxylysinonorleucine and hydroxyproline in skin collagen by reversed-phase high-performance liquid chromatography after 9-fluorenylmethyl chloroformate labeling. Anal Biochem. 1997 Oct 15;252(2):255-9.[9344411 ] Gerling B, Becker M, Waldschmidt J, Rehmann M, Schuppan D: Elevated serum aminoterminal procollagen type-III-peptide parallels collagen accumulation in rats with secondary biliary fibrosis. J Hepatol. 1996 Jul;25(1):79-84.[8836905 ] Bienkowski RS: A criterion to determine whether cis-4-hydroxyproline is produced in animal tissues. Arch Biochem Biophys. 1984 Mar;229(2):455-8.[6703705 ] Bellon G, Berg R, Chastang F, Malgras A, Borel JP: Separation and evaluation of the cis and trans isomers of hydroxyprolines: effect of hydrolysis on the epimerization. Anal Biochem. 1984 Feb;137(1):151-5.[6731795 ] Lindblad WJ, Diegelmann RF: Quantitation of hydroxyproline isomers in acid hydrolysates by high-performance liquid chromatography. Anal Biochem. 1984 May 1;138(2):390-5.[6742416 ] Shibasaki T, Mori H, Ozaki A: Enzymatic production of trans-4-hydroxy-L-proline by regio- and stereospecific hydroxylation of L-proline. Biosci Biotechnol Biochem. 2000 Apr;64(4):746-50.[10830487 ] Pickersgill IF, Rapoport H: Preparation of functionalized, conformationally constrained DTPA analogues from L- or D-serine and trans-4-hydroxy-L-proline. Hydroxymethyl substituents on the central acetic acid and on the backbone. J Org Chem. 2000 Jun 30;65(13):4048-57.[10866623 ] Song IK, Kang YK: Conformational preference and cis-trans isomerization of 4(R)-substituted proline residues. J Phys Chem B. 2006 Feb 2;110(4):1915-27.[16471763 ] Baldwin JE, Pritchard GJ, Williamson DS: The synthesis of 4-arylsulfanyl-substituted kainoid analogues from trans-4-hydroxy-L-proline. Bioorg Med Chem Lett. 2000 Sep 4;10(17):1927-9.[10987419 ] Miskolzie M, Gera L, Stewart JM, Kotovych G: The importance of the N-terminal beta-turn in bradykinin antagonists. J Biomol Struct Dyn. 2000 Oct;18(2):249-60.[11089646 ] Kofoed J, Darbre T, Reymond JL: Dual mechanism of zinc-proline catalyzed aldol reactions in water. Chem Commun (Camb). 2006 Apr 14;(14):1482-4. Epub 2006 Mar 2.[16575434 ] Kuttan R, Radhakrishnan AN: Studies on bound trans-4-hydroxy-L-proline in sandal (Santalum album L.). Biochem J. 1970 Oct;119(4):651-7.[5493503 ]

From T3DB

Taxonomic Classification

Kingdom	Organic compounds
Superclass	Organic acids and derivatives
Class	Carboxylic acids and derivatives
Subclass	Amino acids, peptides, and analogues
Intermediate Tree Nodes	Amino acids and derivatives - Alpha amino acids and derivatives
Direct Parent	Proline and derivatives
Alternative Parents	Organopnictogen compounds Amino acids Pyrrolidine carboxylic acids 1,2-aminoalcohols Monocarboxylic acids and derivatives Carboxylic acids L-alpha-amino acids Hydrocarbon derivatives Dialkylamines Organic oxides Carbonyl compounds Secondary alcohols Azacyclic compounds
Molecular Framework	Aliphatic heteromonocyclic compounds
Substituents	Proline 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
Description	This 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.

From ClassyFire

Targets

Target Details

Proton-coupled amino acid transporter 1

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

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 ]

From T3DB