Target type: biologicalprocess
The chemical reactions and pathways resulting in the breakdown of proteoglycan containing heparan sulfate, any member of a group of glycosaminoglycans that have repeat units consisting of alternating alpha-(1->4) linked hexuronic acid and glucosamine residues, the former being a mixture of sulfated and nonsulfated D-glucuronic and L-iduronic acids, and the latter being either sulfated or acetylated on its amino group as well as sulfated on one of its hydroxyl groups. [GOC:mah, ISBN:0198506732]
Heparan sulfate proteoglycan (HSPG) catabolism is a complex and essential process that involves the degradation of HSPGs, large and diverse molecules that reside on cell surfaces and in the extracellular matrix. HSPGs play crucial roles in various biological functions, including cell signaling, adhesion, and development. Their breakdown is tightly regulated and involves a series of enzymatic steps. The process begins with the action of heparan sulfate (HS) endoglycosidases, such as heparanase, which cleave the HS chains from the core protein. These enzymes often operate in a highly localized manner, targeting specific HSPG subtypes at specific sites. Following HS chain release, the chain undergoes further degradation by a series of exoglycosidases, including sulfatase, glucuronidase, and N-acetylglucosaminidase. These enzymes sequentially remove specific sugar residues from the non-reducing end of the HS chain, resulting in shorter oligosaccharides. These fragments can be further metabolized and utilized by cells. The catabolism of HSPGs is not only essential for the turnover and remodeling of the extracellular matrix, but it also plays a significant role in various cellular processes, including inflammation, angiogenesis, and tumor growth. Dysregulation of HSPG catabolism can contribute to pathological conditions such as cancer and vascular diseases. The process of HSPG catabolism is intricately regulated by a complex interplay of factors, including cellular signaling pathways, growth factors, and the expression and activity of the involved enzymes. Understanding the intricate details of this process is crucial for developing novel therapeutic strategies targeting various diseases.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Beta-galactosidase | A eukaryotic-type beta-galactosidase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P16278] | Homo sapiens (human) |
| Heparanase | A heparanase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y251] | Homo sapiens (human) |
| Beta-galactosidase | A eukaryotic-type beta-galactosidase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P16278] | Homo sapiens (human) |
| Beta-glucuronidase | A beta-glucuronidase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P08236] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| astemizole | astemizole : A piperidine compound having a 2-(4-methoxyphenyl)ethyl group at the 1-position and an N-[(4-fluorobenzyl)benzimidazol-2-yl]amino group at the 4-position. Astemizole: Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects. | benzimidazoles; piperidines | anti-allergic agent; anticoronaviral agent; H1-receptor antagonist |
| cisapride | cisapride : The amide resulting from formal condensation of 4-amino-5-chloro-2-methoxybenzoic acid with cis-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-amine. It has been used (as its monohydrate or as its tartrate) for the treatment of gastro-oesophageal reflux disease and for non-ulcer dyspepsia, but its propensity to cause cardiac arrhythmias resulted in its complete withdrawal from many countries, including the U.K., and restrictions on its use elsewhere. Cisapride: A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed) | benzamides | |
| labetalol | 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide : A member of the class of benzamides that is benzamide substituted by a hydroxy group at position 2 and by a 1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl group at position 5. labetalol : A diastereoisomeric mixture of approximately equal amounts of all four possible stereoisomers ((R,S)-labetolol, (S,R)-labetolol, (S,S)-labetalol and (R,R)-labetalol). It is an adrenergic antagonist used to treat high blood pressure. Labetalol: A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS. | benzamides; benzenes; phenols; primary carboxamide; salicylamides; secondary alcohol; secondary amino compound | |
| dehydroepiandrosterone | dehydroepiandrosterone : An androstanoid that is androst-5-ene substituted by a beta-hydroxy group at position 3 and an oxo group at position 17. It is a naturally occurring steroid hormone produced by the adrenal glands. Dehydroepiandrosterone: A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion. | 17-oxo steroid; 3beta-hydroxy-Delta(5)-steroid; androstanoid | androgen; human metabolite; mouse metabolite |
| galactose | galactopyranose : The pyranose form of galactose. | D-galactose; galactopyranose | Escherichia coli metabolite; mouse metabolite |
| hesperidin | hesperidin : A disaccharide derivative that consists of hesperetin substituted by a 6-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. Hesperidin: A flavanone glycoside found in CITRUS fruit peels. | 3'-hydroxyflavanones; 4'-methoxyflavanones; dihydroxyflavanone; disaccharide derivative; flavanone glycoside; monomethoxyflavanone; rutinoside | mutagen |
| congo red | Congo Red : An indicator dye that is blue-violet at pH 3.0 and red at pH 5.0. Congo Red: An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS. | bis(azo) compound | |
| metergoline | metergoline : An ergoline alkaloid that is the N-benzyloxycarbonyl derivative of lysergamine. A 5-HT2 antagonist. Also 5-HT1 antagonist and 5-HT1D ligand. Has moderate affinity for 5-HT6 and high affinity for 5-HT7. Metergoline: A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy. | carbamate ester; ergoline alkaloid | dopamine agonist; geroprotector; serotonergic antagonist |
| iodophthalein | |||
| methyl methanethiosulfinate | methyl methanethiosulfinate: structure in first source; a metabolite of S-methyl cysteine sulfoxide | sulfur oxoacid derivative | |
| saccharolactone | D-glucaro-1,4-lactone : A delta-lactone that is D-glucono-1,4-lactone in which the hydroxy group at position 6 has been oxidised to the corresponding carboxylic acid. saccharolactone: used as index for assessing induction of hepatic enzymes by anticonvulsants; RN given refers to cpd without isomeric designation | aldarolactone; delta-lactone | |
| migalastat | migalastat: a potent inhibitor of glycolipid biosynthesis | piperidines | |
| naringin | (2S)-flavan-4-one; 4'-hydroxyflavanones; dihydroxyflavanone; disaccharide derivative; neohesperidoside | anti-inflammatory agent; antineoplastic agent; metabolite | |
| isofagomine | piperidines | ||
| 2,2'-dihydroxychalcone | 2,2'-dihydroxychalcone: an antineoplastic agent; structure in first source | ||
| 1-[4-[(2-methyl-4-quinolinyl)amino]phenyl]ethanone | aromatic ketone | ||
| kaempferol | 7-hydroxyflavonol; flavonols; tetrahydroxyflavone | antibacterial agent; geroprotector; human blood serum metabolite; human urinary metabolite; human xenobiotic metabolite; plant metabolite | |
| mangiferin | shamimin: isolated from the leaves of Bombax ceiba; structure in first source | C-glycosyl compound; xanthones | anti-inflammatory agent; antioxidant; hypoglycemic agent; plant metabolite |
| kuwanon g | kuwanon G: a non-peptide bombesin receptor antagonist; RN refers to (1S-(1alpha,5alpha,6beta))-isomer; structure given in first source kuwanone G : A tetrahydroxyflavone isolated from the root barks of Morus alba and has been shown to exhibit anti-inflammatory activity. | resorcinols; tetrahydroxyflavone | anti-inflammatory agent; plant metabolite |
| 2',5'-dihydroxychalcone | 2',5'-dihydroxychalcone: structure given in first source | chalcones | |
| ginkgolide b | |||
| amodiaquine hydrochloride | |||
| b355252 | |||
| phosphomannopentaose sulfate | phosphomannopentaose sulfate: structure in first source | ||
| rk 682 | |||
| pg 545 | PG 545: an anti-angiogenesis agent with heparanase inhibitory activity; structure in first source | ||
| 2-(4-methoxyphenyl)-1H-quinazolin-4-one | quinazolines |