- Signaling Pathways
- Metabolic Enzyme/Protease
Metabolic Enzyme/Protease
Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism.
Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions.
Imbalances in metabolic activities have been found to be critical in a number of pathologies, such as cardiovascular diseases, inflammation, cancer, and neurodegenerative diseases.
- [1] Turk B, et al. EMBO J. 2012 Apr 4;31(7):1630-43.
- [2] Eatemadi A, et al. Biomed Pharmacother. 2017 Feb;86:221-231.
Glucose Metabolism
- Aldose Reductase (143)
- Amylases (115)
- Carbonic Anhydrase (390)
- Carbonyl Reductase (7)
- Creatine Kinase (12)
- Enolase (15)
- FBPase (14)
- FOXO (45)
- Fructose-1,6-bisphosphate aldolase (23)
- Galactokinase (2)
- GHR (26)
- Glucokinase (47)
- Glucose-6-Phosphate Isomerase (GPI) (6)
- Glutathione Peroxidase (261)
- Glycogen Synthase (1)
- Glycosidase (709)
- Glyoxalase (GLO) (27)
- Hexokinase (40)
- HIF/HIF Prolyl-Hydroxylase (404)
- Ketohexokinase (17)
- Lactate Dehydrogenase (137)
- Malate Dehydrogenase (MDH) (13)
- Mineralocorticoid Receptor (67)
- Mitochondrial Metabolism (659)
- NADH Dehydrogenase (8)
- NADPH Oxidase (109)
- NAMPT (96)
- Oxidative Phosphorylation (115)
- PEPCK (7)
- PGC-1α (56)
- Phosphatase (746)
- Phosphoglycerate Dehydrogenase (PHGDH) (22)
- Phosphoglycerate Kinase (PGK) (7)
- Phosphomannose Isomerase (PMI) (6)
- Photosystem II (12)
- Pyruvate Carboxylase (PC) (10)
- Pyruvate Kinase (95)
- Reactive Oxygen Species (ROS) (2988)
- SGK (41)
- Sialyltransferase (22)
- Succinate Dehydrogenase (70)
- Transketolase (14)
- UGT (46)
- β-glucuronidase (54)
Amino Acid/Protein Metabolism
- Acetolactate Synthase (ALS) (42)
- ADAMTS (23)
- Adenosine Deaminase (35)
- Adenosine Kinase (16)
- Amine N-methyltransferase (24)
- Aminopeptidase (146)
- Aminotransferases (Transaminases) (58)
- Angiotensin-converting Enzyme (ACE) (343)
- Arginase (71)
- Carboxypeptidase (34)
- Cathepsin (311)
- COMT (51)
- Dipeptidyl Peptidase (247)
- Dopamine β-hydroxylase (23)
- E1/E2/E3 Enzyme (334)
- Elastase (108)
- Endothelin-Converting Enzyme (ECE) (6)
- Enteropeptidase (11)
- Factor VIIa (8)
- Factor VIII (9)
- Factor Xa (167)
- Factor XI (20)
- Farnesyl Transferase (97)
- Furin (12)
- GGTase (9)
- Glutamate Dehydrogenase (GLDH) (13)
- Glutaminase (77)
- Glutathione Reductase (GR) (11)
- Glutathione S-transferase (101)
- GSNOR (7)
- HCV Protease (87)
- Hepcidin (17)
- HIV Protease (205)
- HPPD (42)
- HSP (524)
- IDE (7)
- Indoleamine 2,3-Dioxygenase (IDO) (165)
- KMO (13)
- MALT1 (35)
- MetAP (29)
- Methionine Adenosyltransferase (MAT) (40)
- Methylenetetrahydrofolate Dehydrogenase (MTHFD) (19)
- MMP (832)
- N-myristoyltransferase (14)
- NEDD8-activating Enzyme (17)
- Neprilysin (72)
- Ornithine decarboxylase (ODC) (10)
- PAI-1 (82)
- PDI (41)
- Plasminogen/Plasmin (16)
- Procollagen C Proteinase (2)
- Prolyl Endopeptidase (PREP) (59)
- Proteasome (302)
- Protein Prenyltransferase (2)
- Proteolytic Enzyme (3)
- Renin (83)
- S-adenosylhomocysteine hydrolase (SAHH) (10)
- Ser/Thr Kinase (58)
- Ser/Thr Protease (385)
- Serine Racemase (SR) (2)
- Serpin (9)
- SHMT (15)
- SULT (7)
- Thrombin (241)
- TMPRSS6 (7)
- Transglutaminase (13)
- Tryptophan Hydroxylase (30)
- Tyrosinase (331)
- Xanthine Oxidase (166)
- γ-Glutamyl Transferase (GGT) (13)
Nucleic Acid Metabolism
- Aminoacyl-tRNA Synthetase (59)
- BTB/POZ Family (2)
- Carbamoyl Phosphate Synthetase (CPS) (5)
- Cryptochrome (13)
- Cytidine Deaminase (12)
- Dihydrofolate reductase (DHFR) (102)
- Dihydroorotate Dehydrogenase (112)
- Dihydropyrimidine Dehydrogenase (DPD) (6)
- Glycolate Oxidase (3)
- HIV Integrase (107)
- IMPDH (12)
- Phosphodiesterase (PDE) (1024)
- TrxR (53)
- Tyrosine Hydroxylase (24)
Lipid Metabolism
- 11β-HSD (83)
- 15-PGDH (17)
- 17β-HSD (165)
- 20α-HSD (2)
- 3α-HSD (3)
- 3β-HSD (7)
- 5 alpha Reductase (58)
- Acetyl-CoA Carboxylase (95)
- Acetyl-CoA synthetase (9)
- ACSL Family (44)
- Acyltransferase (245)
- Adiponectin Receptor (6)
- Aldehyde Dehydrogenase (ALDH) (114)
- Aldehyde Oxidase (AO) (6)
- ANGPTL (21)
- Apolipoprotein (91)
- ATGL (7)
- ATP Citrate Lyase (27)
- Carboxylesterase (CES) (63)
- Carnitine Palmitoyltransferase (CPT) (56)
- Ceramidase (36)
- CETP (39)
- Cytochrome P450 (1285)
- DAGL (14)
- DGK (45)
- Dihydroceramide Desaturase 1 (DES1) (6)
- ELOVL (8)
- Emopamil Binding Protein (3)
- Epoxide Hydrolase (96)
- FAAH (113)
- FABP (35)
- Fat Mass and Obesity-associated Protein (FTO) (35)
- Fatty Acid Synthase (FASN) (122)
- FXR (188)
- HMG-CoA Reductase (HMGCR) (168)
- HRASLS (1)
- IPK Superfamily (14)
- Isocitrate Dehydrogenase (IDH) (74)
- LDLR (95)
- Lipase (132)
- Lipocalin Family (19)
- Liposome (1273)
- Lipoxygenase (319)
- LOX-1 (9)
- LXR (97)
- MAGL (86)
- Malonyl-CoA Decarboxylase (2)
- Microsomal Triglyceride Transfer Protein (MTP) (18)
- Oxysterol-binding Protein-related Protein (ORP) (5)
- PANK (8)
- Pantetheinase (10)
- PCSK9 (114)
- PDHK (39)
- Phospholipase (332)
- Phosphorylase (28)
- PI4P5K (9)
- PNPLA3 (10)
- PPAR (780)
- Quinone Reductase (82)
- RAR/RXR (225)
- REV-ERB (19)
- ROR (152)
- RPE65 (6)
- SPFH Protein Superfamily (1)
- Squalene Monooxygenase (4)
- Squalene Synthase (1)
- Stearoyl-CoA Desaturase (SCD) (61)
- Steroid Sulfatase (27)
Others
- Amino Acid Oxidase (8)
- Branched Chain Amino Acid Transaminase (BCAT) (3)
- Calpain (13)
- Carnosine-cleaving Enzyme (2)
- Dehydrocholesterol Reductase (DHCR) (2)
- FASTK (7)
- Ferrochelatase (6)
- FOXA (1)
- FOXC (1)
- FOXJ (1)
- FOXM1 (19)
- FOXP (22)
- Heme Oxygenase (HO) (115)
- Herbicide (567)
- Hormone-Sensitive Lipase (HSL) (3)
- Liver kinase B1 (LKB1) (1)
- Mitogen- and Stress-Activated Protein Kinase (MSK) (2)
- Myotonin-Protein Kinase (DMPK) (2)
- PASK/STK37 (2)
- Peroxidase Enzyme (1)
- PI5P4K (22)
- Protoporphyrinogen IX oxidase (42)
- RIO Kinase (8)
- SnRK (4)
- TLK (3)
- TSSK (2)
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