790:, which has thiolase activity in peroxisomes, where it may participate in beta oxidation, and in the cytosol, where it participates in the mevalonate pathway. Thiolase is of central importance in key enzymatic pathways such as fatty-acid, steroid and polyketide synthesis. The detailed understanding of its structural biology is of great medical relevance, for example, for a better understanding of the diseases caused by genetic deficiencies of these enzymes and for the development of new antibiotics. Harnessing the complicated catalytic versatility of the polyketide synthases for the synthesis of biologically and medically relevant natural products is also an important future perspective of the studies of the enzymes of this superfamily.
719:
the first step of both the degradative and biosynthetic reactions, the nucleophilic Cys89 (or its equivalent) attacks the acyl-CoA (or 3-ketoacyl-CoA) substrate, leading to the formation of a covalent acyl-enzyme intermediate. In the second step, the addition of CoA (in the degradative reaction) or acetyl-CoA (in the biosynthetic reaction) to the acyl–enzyme intermediate triggers the release of the product from the enzyme. Each of the tetrahedral reaction intermediates that occur during transfer of an acetyl group to and from the nucleophilic cysteine, respectively, have been observed in X-ray crystal structures of biosynthetic thiolase from A. fumigatus.
818:β-Ketothiolase Deficiency has a variable presentation. Most affected patients present between 5 and 24 months of age with symptoms of severe ketoacidosis. Symptoms can be initiated by a dietary protein load, infection or fever. Symptoms progress from vomiting to dehydration and ketoacidosis. Neutropenia and thrombocytopenia may be present, as can moderate hyperammonemia. Blood glucose is typically normal, but can be low or high in acute episodes. Developmental delay may occur, even before the first acute episode, and bilateral striatal
727:
acetyl–enzyme intermediate. Cys89 is activated for nucleophilic attack by His348, which abstracts the sulfide proton of Cys89. In the second step of both the biosynthetic and degradative reactions, the substrate nucleophilically attacks the acetyl–enzyme intermediate to yield the final product and free enzyme. This nucleophilic attack is activated by Cys378, which abstracts a proton from the substrate.
723:
336:
846:
Thompson S, Mayerl F, Peoples OP, Masamune S, Sinskey AJ, Walsh CT (July 1989). "Mechanistic studies on beta-ketoacyl thiolase from
Zoogloea ramigera: identification of the active-site nucleophile as Cys89, its mutation to Ser89, and kinetic and thermodynamic characterization of wild-type and mutant
718:
reaction (reflecting the negative Gibbs energy change of the degradation, which is independent of the thiolase catalyzing the reaction). It is well established from studies on the biosynthetic thiolase from Z. ramigera that the thiolase reaction occurs in two steps and follows ping-pong kinetics. In
481:
There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes are involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the
750:
has been determined at 2.0 Å resolution. The structure contains a striking and novel ‘cage-like’ tetramerization motif, which allows for some hinge motion of the two tight dimers with respect to each other. The enzyme tetramer is acetylated at Cys89 and has a CoA molecule bound in each of its
726:
Thiolase
Mechanism. The two-step, ping-pong mechanism for the thiolase reaction. Red arrows indicate the biosynthetic reaction; Black arrows trace the degradative reaction. In both directions, the reaction is initiated by the nucleophilic attack of Cys89 on the substrate to form a covalent
1086:
Masamune, Satoru; Walsh, Christopher T.; Gamboni, Remo; Thompson, Stuart; Davis, Jeffrey T.; Williams, Simon F.; Peoples, Oliver P.; Sinskey, Anthony J.; Walsh, Christopher T. (1989). "Bio-Claisen condensation catalyzed by thiolase from
Zoogloea ramigera. Active site cysteine residues".
688:
814:
but the long-term clinical consequences, apparently benign, are not well documented. Mitochondrial acetoacetyl-CoA thiolase deficiency is easily diagnosed by urinary organic acid analysis and can be confirmed by enzymatic analysis of cultured skin fibroblasts or blood leukocytes.
377:
pathway of fatty acid degradation and various biosynthetic pathways. Members of the thiolase family can be divided into two broad categories: degradative thiolases (EC 2.3.1.16) and biosynthetic thiolases (EC 2.3.1.9). These two different types of thiolase are found both in
471:). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of
675:) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in
394:
thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the
952:
Baker ME, Billheimer JT, Strauss JF (November 1991). "Similarity between the amino-terminal portion of mammalian 58-kD sterol carrier protein (SCPx) and
Escherichia coli acetyl-CoA acyltransferase: evidence for a gene fusion in SCPx".
988:
Yang SY, Yang XY, Healy-Louie G, Schulz H, Elzinga M (June 1990). "Nucleotide sequence of the fadA gene. Primary structure of 3-ketoacyl-coenzyme A thiolase from
Escherichia coli and the structural organization of the fadAB operon".
1344:
Middleton B, Bartlett K (March 1983). "The synthesis and characterisation of 2-methylacetoacetyl coenzyme A and its use in the identification of the site of the defect in 2-methylacetoacetic and 2-methyl-3-hydroxybutyric aciduria".
763:
cells, especially in mammalian cells, thiolases exhibit diversity in intracellular localization related to their metabolic functions as well as in substrate specificity. For example, they contribute to fatty-acid β-oxidation in
713:
All thiolases, whether they are biosynthetic or degradative in vivo, preferentially catalyze the degradation of 3-ketoacyl-CoA to form acetyl-CoA and a shortened acyl-CoA species, but are also capable of catalyzing the reverse
1183:
Marshall, Andrew C.; Bond, Charles S.; Bruning, John B. (January 25, 2018). "Structure of
Aspergillus fumigatus Cytosolic Thiolase: Trapped Tetrahedral Reaction Intermediates and Activation by Monovalent Cations".
2138:
784:. In addition to biochemical investigations, analyses of genetic disorders have made clear the basis of their functions. Genetic studies have identified a three-thiolase system in the yeast
2131:
1432:
Ueda M, Kanayama N, Tanaka A (2000). "Genetic evaluation of peroxisomal and cytosolic acetoacetyl-CoA thiolase isozymes in n-alkane-assimilating diploid yeast, Candida tropicalis".
744:
are observed only in the thiolase subfamily and, in these cases, the dimers have dimerized to become tetramers. The crystal structure of the tetrameric biosynthetic thiolase from
698:
are more reactive than oxygen esters and are common intermediates in fatty-acid metabolism. These thioesters are made by conjugating the fatty acid with the free SH group of the
2124:
1642:
Robinson BH, Sherwood WG, Taylor J, Balfe JW, Mamer OA (August 1979). "Acetoacetyl CoA thiolase deficiency: a cause of severe ketoacidosis in infancy simulating salicylism".
1019:
Igual JC, González-Bosch C, Dopazo J, Pérez-Ortín JE (August 1992). "Phylogenetic analysis of the thiolase family. Implications for the evolutionary origin of peroxisomes".
1143:"The 1.8 A crystal structure of the dimeric peroxisomal 3-ketoacyl-CoA thiolase of Saccharomyces cerevisiae: implications for substrate binding and reaction mechanism"
608:
303:
162:
1955:
1950:
1756:
2508:
2503:
1938:
2334:
1114:
Gilbert HF, Lennox BJ, Mossman CD, Carle WC (July 1981). "The relation of acyl transfer to the overall reaction of thiolase I from porcine heart".
2280:
2698:
2448:
1945:
917:
Haapalainen AM, Meriläinen G, Wierenga RK (January 2006). "The thiolase superfamily: condensing enzymes with diverse reaction specificities".
1599:
1070:
251:
98:
2217:
1933:
1223:"A biosynthetic thiolase in complex with a reaction intermediate: the crystal structure provides new insights into the catalytic mechanism"
31:
2116:
2636:
2592:
2495:
2275:
2105:
2584:
2520:
2073:
1889:
1827:
1884:
1879:
2392:
2222:
1822:
1508:
Keatinge-Clay AT, Maltby DA, Medzihradszky KF, Khosla C, Stroud RM (September 2004). "An antibiotic factory caught in action".
652:
1384:"Genetic evaluation of physiological functions of thiolase isoenzymes in the n-alkalane-assimilating yeast Candida tropicalis"
478:
In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.
2373:
1837:
1749:
1615:
Hillman RE, Keating JP (February 1974). "Beta-ketothiolase deficiency as a cause of the "ketotic hyperglycinemia syndrome"".
518:
450:
323:
182:
1590:
Mitchell GA, Fukao T (2001). "Inborn errors of ketone body metabolism". In
Scriver CR, Beaudet AL, Sly WS, Valle D (eds.).
2708:
2415:
2363:
2296:
2002:
1982:
1896:
1923:
1817:
1812:
799:
679:. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases.
556:
461:
387:
35:
2703:
2257:
2085:
1859:
1469:"Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism"
2095:
1928:
1802:
803:
1552:
2368:
2043:
2019:
1970:
1854:
1807:
1782:
1742:
118:
2747:
2270:
2048:
1773:
1683:
644:
630:
622:
600:
548:
510:
465:
454:
404:
311:
170:
2090:
1997:
2339:
2058:
2053:
1918:
1679:
475:
and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.
2301:
2038:
2033:
307:
166:
1314:"Metabolism of acetyl-CoA by isolated peroxisomal fractions: formation of acetate and acetoacetyl-CoA"
2473:
2354:
2100:
1987:
1974:
1874:
715:
707:
427:
264:
111:
123:
2344:
1832:
17:
2659:
2175:
2167:
1533:
1044:
786:
777:
741:
363:
2545:
810:
and ketone body metabolism. The major clinical manifestations of this disorder are intermittent
1313:
2670:
2600:
2265:
2246:
2063:
1792:
1711:
1690:
1659:
1624:
1595:
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1414:
1364:
1326:
1294:
1244:
1165:
1123:
1066:
1036:
998:
970:
934:
899:
864:
746:
687:
298:
157:
2678:
2198:
2151:
2028:
1992:
1651:
1564:
1517:
1480:
1441:
1404:
1396:
1356:
1347:
1284:
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1234:
1201:
1193:
1155:
1096:
1028:
962:
926:
891:
856:
290:
149:
2430:
2068:
1769:
1734:
472:
414:
The formation of a carbon–carbon bond is a key step in the biosynthetic pathways by which
400:
359:
2540:
2459:
2238:
1289:
1263:
442:
391:
374:
1655:
1568:
1409:
1383:
1239:
1222:
2741:
1720:
1699:
1388:
1360:
1318:
1147:
823:
737:
256:
103:
1537:
1048:
220:
67:
2440:
811:
769:
722:
449:. Two different types of thiolase are found both in eukaryotes and in prokaryotes:
286:
145:
1400:
335:
2733:
1445:
232:
79:
2556:
2468:
2383:
2316:
2227:
2209:
2159:
2007:
1765:
1268:
773:
765:
699:
676:
415:
383:
930:
2326:
2147:
807:
760:
703:
695:
419:
379:
355:
1197:
2664:
2631:
2485:
2407:
966:
781:
396:
1529:
1494:
1485:
1468:
1453:
1248:
1160:
1142:
938:
903:
1628:
1576:
1418:
1368:
1330:
1298:
1169:
1127:
1040:
1002:
974:
868:
260:
107:
2729:
2623:
2566:
2481:
882:
Heath RJ, Rock CO (October 2002). "The
Claisen condensation in biology".
819:
647:
625:
603:
227:
74:
1663:
1100:
860:
551:
468:
2689:
2684:
2579:
2574:
2490:
2420:
2185:
2163:
1725:
1715:
1704:
1694:
1206:
1032:
513:
457:
446:
423:
408:
370:
244:
239:
91:
86:
1280:
373:
that have key roles in many vital biochemical pathways, including the
2610:
2605:
2533:
2528:
2155:
2078:
1906:
1901:
1842:
895:
671:
Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as
318:
177:
1521:
798:
Mitochondrial acetoacetyl-CoA thiolase deficiency, known earlier as
426:
catalyse the carbon–carbon-bond formation via a thioester-dependent
1467:
Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO (March 2001).
1960:
1847:
721:
590:
580:
570:
538:
528:
2725:
1864:
672:
660:
280:
215:
139:
62:
2120:
1738:
827:
1710:
Overview of all the structural information available in the
1689:
Overview of all the structural information available in the
1141:
Mathieu M, Modis Y, Zeelen JP, et al. (October 1997).
1592:
The metabolic & molecular bases of inherited disease
1551:
Daum RS, Lamm PH, Mamer OA, Scriver CR (December 1971).
1312:
Hovik R, Brodal B, Bartlett K, Osmundsen H (June 1991).
1382:
Kanayama N, Ueda M, Atomi H, Tanaka A (February 1998).
2724:
This article incorporates text from the public domain
2638:
2594:
2586:
2522:
2497:
1264:"The oxoacyl-coenzyme A thiolases of animal tissues"
2652:
2621:
2564:
2554:
2457:
2438:
2429:
2405:
2382:
2353:
2324:
2314:
2289:
2255:
2236:
2208:
2183:
2174:
2018:
1969:
1781:
776:metabolism in mitochondria, and the early steps of
317:
297:
279:
274:
250:
238:
226:
214:
206:
201:
196:
176:
156:
138:
133:
117:
97:
85:
73:
61:
53:
48:
43:
1724:(3-ketoacyl-CoA thiolase 2, peroxisomal ) at the
609:Propionyl-CoA C2-trimethyltridecanoyltransferase
403:and involved in biosynthetic pathways such as
2132:
1750:
1594:. New York: McGraw-Hill. pp. 2326–2356.
1014:
1012:
736:Most enzymes of the thiolase superfamily are
8:
1956:2-acylglycerol-3-phosphate O-acyltransferase
1951:1-acylglycerol-3-phosphate O-acyltransferase
740:. However, monomers have not been observed.
386:: acetoacetyl-CoA thiolase (EC:2.3.1.9) and
1553:"A "new" disorder of isoleucine catabolism"
354:), are enzymes which convert two units of
2561:
2435:
2321:
2180:
2139:
2125:
2117:
1757:
1743:
1735:
271:
130:
1682:at the U.S. National Library of Medicine
1484:
1408:
1288:
1238:
1205:
1159:
2335:Farnesyl-diphosphate farnesyltransferase
686:
489:
334:
2281:Isopentenyl-diphosphate delta isomerase
838:
2699:Steroidogenic acute regulatory protein
1946:Glycerol-3-phosphate O-acyltransferase
1065:. San Francisco: W. H. Freeman. 1979.
193:
40:
1939:Lecithin—cholesterol acyltransferase
1221:Modis Y, Wierenga RK (October 1999).
7:
1934:Glyceronephosphate O-acyltransferase
348:acetyl-coenzyme A acetyltransferases
32:Acyl-CoA:cholesterol acyltransferase
2276:Pyrophosphomevalonate decarboxylase
2194:Acetyl-Coenzyme A acetyltransferase
2106:Sulfoacetaldehyde acetyltransferase
1798:Acetyl-Coenzyme A acetyltransferase
422:are made. The thiolase superfamily
2022:: converted into alkyl on transfer
25:
18:Long-chain 3-ketoacyl CoA thiolase
1828:Chloramphenicol acetyltransferase
1703:(3-ketoacyl-CoA thiolase) at the
1880:Carnitine O-palmitoyltransferase
1434:Cell Biochemistry and Biophysics
2449:Cholesterol side-chain cleavage
2393:24-Dehydrocholesterol reductase
2223:3-hydroxybutyrate dehydrogenase
1823:Beta-galactoside transacetylase
653:Propanoyl-CoA C-acyltransferase
2374:7-Dehydrocholesterol reductase
1838:Serotonin N-acetyl transferase
1785:: other than amino-acyl groups
1680:Acetyl-CoA+C-Acetyltransferase
691:Reaction catalyzed by thiolase
519:Acetyl-CoA C-acetyltransferase
1:
2709:Reverse cholesterol transport
2297:Dimethylallyltranstransferase
2003:Keratinocyte transglutaminase
1983:Gamma-glutamyl transpeptidase
1897:Serine C-palmitoyltransferase
1656:10.1016/S0022-3476(79)80658-7
1569:10.1016/S0140-6736(71)90605-2
1401:10.1128/JB.180.3.690-698.1998
1240:10.1016/S0969-2126(00)80061-1
1063:Enzymatic reaction mechanisms
275:Available protein structures:
134:Available protein structures:
1924:Aminolevulinic acid synthase
1818:Acetyl-CoA C-acyltransferase
1813:Dihydrolipoyl transacetylase
1361:10.1016/0009-8981(83)90329-7
613:3-Oxopristanoyl-CoA thiolase
557:Acetyl-CoA C-acyltransferase
36:Acetyl-CoA C-acyltransferase
2704:Cholesterol total synthesis
2086:2-hydroxyglutarate synthase
197:Thiolase, C-terminal domain
44:Thiolase, N-terminal domain
2764:
2723:
2416:Cholesterol 7α-hydroxylase
2364:Lanosterol 14α-demethylase
2096:2-isopropylmalate synthase
1929:Beta-ketoacyl-ACP synthase
1803:N-Acetylglutamate synthase
1262:Middleton B (April 1973).
931:10.1016/j.tibs.2005.11.011
804:inborn error of metabolism
445:of evolutionarily related
29:
2369:Sterol-C5-desaturase-like
2044:Decylhomocitrate synthase
1855:Histone acetyltransferase
1808:Choline acetyltransferase
800:β-ketothiolase deficiency
635:β-Ketoadipyl-CoA thiolase
560:
555:
547:
522:
517:
509:
505:Subcellular distribution
369:Thiolases are ubiquitous
270:
129:
2271:Phosphomevalonate kinase
2049:2-methylcitrate synthase
1684:Medical Subject Headings
1198:10.1021/acscatal.7b02873
673:sterol carrier protein 2
631:3-Oxoadipyl-CoA thiolase
563:3-Ketoacyl-CoA thiolase;
525:Acetoacetyl-CoA thiolase
451:acetoacetyl-CoA thiolase
405:beta-hydroxybutyric acid
30:Not to be confused with
2091:3-propylmalate synthase
1998:Tissue transglutaminase
967:10.1089/dna.1991.10.695
826:has been seen on brain
482:condensation reaction.
462:3-ketoacyl-CoA thiolase
388:3-ketoacyl-CoA thiolase
2340:Squalene monooxygenase
2059:3-ethylmalate synthase
2054:2-ethylmalate synthase
1919:Acyltransferase like 2
1510:Nat. Struct. Mol. Biol
1486:10.1074/jbc.M007101200
1446:10.1385/cbb:32:1-3:285
1161:10.1006/jmbi.1997.1331
728:
692:
665:peroxisomal/cytosolic
657:Peroxisomal thiolase 2
340:
2421:Sterol 27-hydroxylase
2302:Geranyl pyrophosphate
2039:Citrate (Re)-synthase
2034:Decylcitrate synthase
1975:Aminoacyltransferases
1875:palmitoyltransferases
808:isoleucine catabolism
751:active-site pockets.
725:
690:
338:
2355:7-Dehydrocholesterol
2101:Homocitrate synthase
1988:Peptidyl transferase
716:Claisen condensation
708:acyl carrier protein
430:reaction mechanism.
428:Claisen condensation
2345:Lanosterol synthase
1833:N-acetyltransferase
1440:(Spring): 285–290.
1101:10.1021/ja00187a053
919:Trends Biochem. Sci
861:10.1021/bi00440a006
780:in peroxisomes and
755:Biological function
2660:Steroid metabolism
2176:Mevalonate pathway
2168:steroid metabolism
1793:acetyltransferases
1033:10.1007/BF00183226
787:Candida tropicalis
778:mevalonate pathway
729:
693:
364:mevalonate pathway
341:
339:Mevalonate pathway
2721:
2720:
2717:
2716:
2671:Steroid sulfatase
2648:
2647:
2401:
2400:
2310:
2309:
2266:Mevalonate kinase
2247:HMG-CoA reductase
2114:
2113:
2064:ATP citrate lyase
1601:978-0-07-913035-8
1563:(7737): 1289–90.
1281:10.1042/bj1320717
1095:(5): 1879, 1991.
1072:978-0-7167-0070-8
794:Disease relevance
747:Zoogloea ramigera
702:moiety of either
669:
668:
333:
332:
329:
328:
324:structure summary
192:
191:
188:
187:
183:structure summary
16:(Redirected from
2755:
2679:sulfotransferase
2640:
2596:
2588:
2562:
2524:
2499:
2436:
2322:
2201:(regulated step)
2199:HMG-CoA synthase
2181:
2152:lipid metabolism
2141:
2134:
2127:
2118:
2074:HMG-CoA synthase
2029:Citrate synthase
1993:Transglutaminase
1770:acyltransferases
1759:
1752:
1745:
1736:
1668:
1667:
1639:
1633:
1632:
1612:
1606:
1605:
1587:
1581:
1580:
1548:
1542:
1541:
1505:
1499:
1498:
1488:
1464:
1458:
1457:
1429:
1423:
1422:
1412:
1379:
1373:
1372:
1355:(2–3): 291–305.
1348:Clin. Chim. Acta
1341:
1335:
1334:
1309:
1303:
1302:
1292:
1259:
1253:
1252:
1242:
1218:
1212:
1211:
1209:
1192:(3): 1973–1989.
1180:
1174:
1173:
1163:
1138:
1132:
1131:
1111:
1105:
1104:
1089:J. Am. Chem. Soc
1083:
1077:
1076:
1059:
1053:
1052:
1016:
1007:
1006:
985:
979:
978:
949:
943:
942:
914:
908:
907:
896:10.1039/b110221b
879:
873:
872:
843:
490:
346:, also known as
272:
194:
131:
41:
21:
2763:
2762:
2758:
2757:
2756:
2754:
2753:
2752:
2748:Protein domains
2738:
2737:
2736:
2722:
2713:
2653:Other/ungrouped
2644:
2617:
2575:17α-Hydroxylase
2550:
2546:11β-Hydroxylase
2491:17α-Hydroxylase
2460:corticosteroids
2453:
2431:Steroidogenesis
2425:
2397:
2378:
2349:
2306:
2285:
2251:
2232:
2204:
2170:
2145:
2115:
2110:
2069:Malate synthase
2014:
1965:
1777:
1763:
1732:
1676:
1671:
1641:
1640:
1636:
1614:
1613:
1609:
1602:
1589:
1588:
1584:
1550:
1549:
1545:
1522:10.1038/nsmb808
1507:
1506:
1502:
1466:
1465:
1461:
1431:
1430:
1426:
1381:
1380:
1376:
1343:
1342:
1338:
1311:
1310:
1306:
1261:
1260:
1256:
1233:(10): 1279–90.
1220:
1219:
1215:
1182:
1181:
1177:
1140:
1139:
1135:
1113:
1112:
1108:
1085:
1084:
1080:
1073:
1061:
1060:
1056:
1018:
1017:
1010:
997:(18): 10424–9.
987:
986:
982:
951:
950:
946:
916:
915:
911:
881:
880:
876:
855:(14): 5735–42.
845:
844:
840:
836:
796:
757:
734:
685:
566:
564:
562:
524:
488:
473:acetoacetyl-CoA
436:
401:acetoacetyl-CoA
390:(EC:2.3.1.16).
360:acetoacetyl CoA
39:
28:
23:
22:
15:
12:
11:
5:
2761:
2759:
2751:
2750:
2740:
2739:
2719:
2718:
2715:
2714:
2712:
2711:
2706:
2701:
2695:
2694:
2693:
2692:
2687:
2675:
2674:
2673:
2656:
2654:
2650:
2649:
2646:
2645:
2643:
2642:
2634:
2628:
2626:
2619:
2618:
2616:
2615:
2614:
2613:
2608:
2598:
2590:
2582:
2577:
2571:
2569:
2559:
2552:
2551:
2549:
2548:
2543:
2541:21-Hydroxylase
2538:
2537:
2536:
2531:
2514:
2513:
2512:
2511:
2506:
2493:
2477:
2476:
2474:18-Hydroxylase
2464:
2462:
2455:
2454:
2452:
2451:
2445:
2443:
2433:
2427:
2426:
2424:
2423:
2418:
2412:
2410:
2403:
2402:
2399:
2398:
2396:
2395:
2389:
2387:
2380:
2379:
2377:
2376:
2371:
2366:
2360:
2358:
2351:
2350:
2348:
2347:
2342:
2337:
2331:
2329:
2319:
2312:
2311:
2308:
2307:
2305:
2304:
2299:
2293:
2291:
2287:
2286:
2284:
2283:
2278:
2273:
2268:
2262:
2260:
2253:
2252:
2250:
2249:
2243:
2241:
2239:Mevalonic acid
2234:
2233:
2231:
2230:
2225:
2220:
2214:
2212:
2206:
2205:
2203:
2202:
2196:
2190:
2188:
2178:
2172:
2171:
2146:
2144:
2143:
2136:
2129:
2121:
2112:
2111:
2109:
2108:
2103:
2098:
2093:
2088:
2083:
2082:
2081:
2071:
2066:
2061:
2056:
2051:
2046:
2041:
2036:
2031:
2025:
2023:
2016:
2015:
2013:
2012:
2011:
2010:
2005:
2000:
1990:
1985:
1979:
1977:
1967:
1966:
1964:
1963:
1958:
1953:
1948:
1942:
1941:
1936:
1931:
1926:
1921:
1912:
1911:
1910:
1909:
1904:
1894:
1893:
1892:
1887:
1870:
1869:
1868:
1867:
1862:
1852:
1851:
1850:
1845:
1840:
1830:
1825:
1820:
1815:
1810:
1805:
1800:
1788:
1786:
1779:
1778:
1764:
1762:
1761:
1754:
1747:
1739:
1730:
1729:
1708:
1687:
1675:
1674:External links
1672:
1670:
1669:
1634:
1607:
1600:
1582:
1543:
1500:
1459:
1424:
1374:
1336:
1304:
1254:
1213:
1175:
1133:
1122:(14): 7371–7.
1106:
1078:
1071:
1054:
1008:
980:
944:
909:
874:
837:
835:
832:
795:
792:
756:
753:
733:
730:
684:
681:
667:
666:
663:
658:
655:
650:
641:
640:
638:
636:
633:
628:
619:
618:
616:
614:
611:
606:
597:
596:
595:mitochondrial
593:
587:
586:
585:mitochondrial
583:
577:
576:
573:
568:
565:β-Ketothiolase
559:
554:
545:
544:
541:
535:
534:
533:mitochondrial
531:
526:
521:
516:
507:
506:
503:
500:
499:Alternate name
497:
494:
487:
484:
435:
432:
392:3-ketoacyl-CoA
375:beta oxidation
331:
330:
327:
326:
321:
315:
314:
301:
295:
294:
284:
277:
276:
268:
267:
254:
248:
247:
242:
236:
235:
230:
224:
223:
218:
212:
211:
208:
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203:
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180:
174:
173:
160:
154:
153:
143:
136:
135:
127:
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115:
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101:
95:
94:
89:
83:
82:
77:
71:
70:
65:
59:
58:
55:
51:
50:
46:
45:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
2760:
2749:
2746:
2745:
2743:
2735:
2731:
2727:
2710:
2707:
2705:
2702:
2700:
2697:
2696:
2691:
2688:
2686:
2683:
2682:
2681:
2680:
2676:
2672:
2669:
2668:
2667:
2666:
2661:
2658:
2657:
2655:
2651:
2641:
2635:
2633:
2630:
2629:
2627:
2625:
2620:
2612:
2609:
2607:
2604:
2603:
2602:
2599:
2597:
2591:
2589:
2583:
2581:
2578:
2576:
2573:
2572:
2570:
2568:
2563:
2560:
2558:
2553:
2547:
2544:
2542:
2539:
2535:
2532:
2530:
2527:
2526:
2525:
2519:
2516:
2515:
2510:
2507:
2505:
2502:
2501:
2500:
2494:
2492:
2489:
2487:
2483:
2479:
2478:
2475:
2472:
2470:
2466:
2465:
2463:
2461:
2456:
2450:
2447:
2446:
2444:
2442:
2437:
2434:
2432:
2428:
2422:
2419:
2417:
2414:
2413:
2411:
2409:
2404:
2394:
2391:
2390:
2388:
2385:
2381:
2375:
2372:
2370:
2367:
2365:
2362:
2361:
2359:
2356:
2352:
2346:
2343:
2341:
2338:
2336:
2333:
2332:
2330:
2328:
2323:
2320:
2318:
2313:
2303:
2300:
2298:
2295:
2294:
2292:
2288:
2282:
2279:
2277:
2274:
2272:
2269:
2267:
2264:
2263:
2261:
2259:
2254:
2248:
2245:
2244:
2242:
2240:
2235:
2229:
2226:
2224:
2221:
2219:
2218:HMG-CoA lyase
2216:
2215:
2213:
2211:
2207:
2200:
2197:
2195:
2192:
2191:
2189:
2187:
2182:
2179:
2177:
2173:
2169:
2165:
2161:
2157:
2153:
2149:
2142:
2137:
2135:
2130:
2128:
2123:
2122:
2119:
2107:
2104:
2102:
2099:
2097:
2094:
2092:
2089:
2087:
2084:
2080:
2077:
2076:
2075:
2072:
2070:
2067:
2065:
2062:
2060:
2057:
2055:
2052:
2050:
2047:
2045:
2042:
2040:
2037:
2035:
2032:
2030:
2027:
2026:
2024:
2021:
2017:
2009:
2006:
2004:
2001:
1999:
1996:
1995:
1994:
1991:
1989:
1986:
1984:
1981:
1980:
1978:
1976:
1972:
1968:
1962:
1959:
1957:
1954:
1952:
1949:
1947:
1944:
1943:
1940:
1937:
1935:
1932:
1930:
1927:
1925:
1922:
1920:
1917:
1914:
1913:
1908:
1905:
1903:
1900:
1899:
1898:
1895:
1891:
1888:
1886:
1883:
1882:
1881:
1878:
1876:
1872:
1871:
1866:
1863:
1861:
1858:
1857:
1856:
1853:
1849:
1846:
1844:
1841:
1839:
1836:
1835:
1834:
1831:
1829:
1826:
1824:
1821:
1819:
1816:
1814:
1811:
1809:
1806:
1804:
1801:
1799:
1796:
1794:
1790:
1789:
1787:
1784:
1780:
1775:
1771:
1767:
1760:
1755:
1753:
1748:
1746:
1741:
1740:
1737:
1733:
1727:
1723:
1722:
1717:
1713:
1709:
1706:
1702:
1701:
1696:
1692:
1688:
1685:
1681:
1678:
1677:
1673:
1665:
1661:
1657:
1653:
1650:(2): 228–33.
1649:
1645:
1638:
1635:
1630:
1626:
1622:
1618:
1611:
1608:
1603:
1597:
1593:
1586:
1583:
1578:
1574:
1570:
1566:
1562:
1558:
1554:
1547:
1544:
1539:
1535:
1531:
1527:
1523:
1519:
1516:(9): 888–93.
1515:
1511:
1504:
1501:
1496:
1492:
1487:
1482:
1479:(9): 6551–9.
1478:
1474:
1473:J. Biol. Chem
1470:
1463:
1460:
1455:
1451:
1447:
1443:
1439:
1435:
1428:
1425:
1420:
1416:
1411:
1406:
1402:
1398:
1394:
1391:
1390:
1389:J. Bacteriol.
1385:
1378:
1375:
1370:
1366:
1362:
1358:
1354:
1350:
1349:
1340:
1337:
1332:
1328:
1324:
1321:
1320:
1319:J. Lipid Res.
1315:
1308:
1305:
1300:
1296:
1291:
1286:
1282:
1278:
1275:(4): 717–30.
1274:
1271:
1270:
1265:
1258:
1255:
1250:
1246:
1241:
1236:
1232:
1228:
1224:
1217:
1214:
1208:
1203:
1199:
1195:
1191:
1187:
1186:ACS Catalysis
1179:
1176:
1171:
1167:
1162:
1157:
1154:(3): 714–28.
1153:
1150:
1149:
1148:J. Mol. Biol.
1144:
1137:
1134:
1129:
1125:
1121:
1117:
1116:J. Biol. Chem
1110:
1107:
1102:
1098:
1094:
1090:
1082:
1079:
1074:
1068:
1064:
1058:
1055:
1050:
1046:
1042:
1038:
1034:
1030:
1027:(2): 147–55.
1026:
1022:
1015:
1013:
1009:
1004:
1000:
996:
992:
991:J. Biol. Chem
984:
981:
976:
972:
968:
964:
960:
956:
955:DNA Cell Biol
948:
945:
940:
936:
932:
928:
924:
920:
913:
910:
905:
901:
897:
893:
890:(5): 581–96.
889:
885:
878:
875:
870:
866:
862:
858:
854:
850:
842:
839:
833:
831:
829:
825:
824:basal ganglia
821:
816:
813:
809:
805:
801:
793:
791:
789:
788:
783:
779:
775:
771:
767:
762:
754:
752:
749:
748:
743:
739:
731:
724:
720:
717:
711:
709:
705:
701:
697:
689:
682:
680:
678:
674:
664:
662:
659:
656:
654:
651:
649:
646:
643:
642:
639:
637:
634:
632:
629:
627:
624:
621:
620:
617:
615:
612:
610:
607:
605:
602:
599:
598:
594:
592:
589:
588:
584:
582:
579:
578:
574:
572:
569:
558:
553:
550:
546:
542:
540:
537:
536:
532:
530:
527:
520:
515:
512:
508:
504:
501:
498:
495:
492:
491:
485:
483:
479:
476:
474:
470:
467:
463:
459:
456:
452:
448:
444:
440:
433:
431:
429:
425:
421:
417:
412:
410:
407:synthesis or
406:
402:
398:
393:
389:
385:
381:
376:
372:
367:
365:
361:
357:
353:
349:
345:
337:
325:
322:
320:
316:
313:
309:
305:
302:
300:
296:
292:
288:
285:
282:
278:
273:
269:
266:
262:
258:
255:
253:
249:
246:
243:
241:
237:
234:
231:
229:
225:
222:
219:
217:
213:
209:
205:
200:
195:
184:
181:
179:
175:
172:
168:
164:
161:
159:
155:
151:
147:
144:
141:
137:
132:
128:
125:
122:
120:
116:
113:
109:
105:
102:
100:
96:
93:
90:
88:
84:
81:
78:
76:
72:
69:
66:
64:
60:
56:
52:
47:
42:
37:
33:
19:
2677:
2663:
2601:5α-Reductase
2557:sex hormones
2517:
2480:
2467:
2441:pregnenolone
2193:
1915:
1873:
1797:
1791:
1766:Transferases
1731:
1719:
1698:
1647:
1643:
1637:
1623:(2): 221–5.
1620:
1616:
1610:
1591:
1585:
1560:
1556:
1546:
1513:
1509:
1503:
1476:
1472:
1462:
1437:
1433:
1427:
1395:(3): 690–8.
1392:
1387:
1377:
1352:
1346:
1339:
1325:(6): 993–9.
1322:
1317:
1307:
1272:
1267:
1257:
1230:
1226:
1216:
1189:
1185:
1178:
1151:
1146:
1136:
1119:
1115:
1109:
1092:
1088:
1081:
1062:
1057:
1024:
1021:J. Mol. Evol
1020:
994:
990:
983:
961:(9): 695–8.
958:
954:
947:
925:(1): 64–71.
922:
918:
912:
887:
884:Nat Prod Rep
883:
877:
852:
849:Biochemistry
848:
841:
817:
812:ketoacidosis
797:
785:
770:mitochondria
758:
745:
735:
712:
694:
670:
575:peroxisomal
523:thiolase II;
480:
477:
438:
437:
413:
411:biogenesis.
368:
351:
347:
343:
342:
2580:17,20-Lyase
2469:aldosterone
2384:Desmosterol
2317:cholesterol
2228:Thiophorase
2210:Ketogenesis
2160:cholesterol
2008:Factor XIII
1269:Biochem. J.
1207:2440/113865
774:ketone body
766:peroxisomes
700:pantetheine
677:peroxisomes
561:thiolase I;
416:fatty acids
384:prokaryotes
202:Identifiers
49:Identifiers
2408:Bile acids
2327:lanosterol
2162:synthesis
2148:Metabolism
1644:J. Pediatr
1617:Pediatrics
847:enzymes".
834:References
806:involving
761:eukaryotic
704:coenzyme A
696:Thioesters
543:cytosolic
420:polyketide
380:eukaryotes
356:acetyl-CoA
287:structures
210:Thiolase_C
146:structures
57:Thiolase_N
2734:IPR002155
2665:sulfatase
2632:Aromatase
2624:estrogens
2567:androgens
2486:cortisone
1227:Structure
782:cytoplasm
742:Tetramers
732:Structure
706:(CoA) or
683:Mechanism
648:2.3.1.176
626:2.3.1.174
604:2.3.1.154
493:EC number
439:Thiolases
397:thiolysis
344:Thiolases
245:PDOC00092
233:IPR002155
92:PDOC00092
80:IPR002155
2742:Category
2730:InterPro
2482:cortisol
2290:Geranyl-
1860:P300/CBP
1538:12394083
1530:15286722
1495:11050088
1454:11330060
1249:10545327
1049:39746646
939:16356722
904:12430724
820:necrosis
802:, is an
552:2.3.1.16
502:Isozymes
486:Isozymes
469:2.3.1.16
443:a family
434:Function
304:RCSB PDB
228:InterPro
163:RCSB PDB
75:InterPro
2690:SULT2A1
2685:SULT1A1
2186:HMG-CoA
2164:enzymes
2156:ketones
1726:PDBe-KB
1716:UniProt
1705:PDBe-KB
1695:UniProt
1629:4812006
1577:4143539
1419:9457876
1369:6133656
1331:1682408
1299:4721607
1290:1177647
1170:9402066
1128:6114098
1041:1354266
1003:2191949
975:1755959
869:2775734
822:of the
710:(ACP).
514:2.3.1.9
458:2.3.1.9
447:enzymes
424:enzymes
409:steroid
382:and in
371:enzymes
362:in the
240:PROSITE
221:PF02803
124:cd00751
87:PROSITE
68:PF00108
27:Enzymes
2079:HMGCS2
1916:other:
1907:SPTLC2
1902:SPTLC1
1843:HGSNAT
1721:Q56WD9
1700:P28790
1686:(MeSH)
1662:
1627:
1598:
1575:
1557:Lancet
1536:
1528:
1493:
1452:
1417:
1410:106940
1407:
1367:
1329:
1297:
1287:
1247:
1168:
1126:
1069:
1047:
1039:
1001:
973:
937:
902:
867:
738:dimers
460:) and
319:PDBsum
293:
283:
265:SUPFAM
207:Symbol
178:PDBsum
152:
142:
112:SUPFAM
54:Symbol
2518:both:
2258:DMAPP
2020:2.3.3
1971:2.3.2
1961:ABHD5
1848:ARD1A
1783:2.3.1
1664:36452
1534:S2CID
1045:S2CID
591:HADHB
581:ACAA2
571:ACAA1
567:3-KAT
539:ACAT2
529:ACAT1
261:SCOPe
252:SCOP2
108:SCOPe
99:SCOP2
2728:and
2726:Pfam
2637:17β-
2593:17β-
2496:11β-
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