Loading Pathway...

Error: Pathway image not found.

Hide

Description
Highlight
Analyze
Downloads
Settings

Pathway Description

Cholesterol Biosynthesis and Metabolism CE(10:0)

Saccharomyces cerevisiae

Category:

Metabolite Pathway

Sub-Category:

Metabolic

Created: 2016-05-11

Last Updated: 2025-01-30

The biosynthesis of Cholesterol starts with acetyl-CoA reacts with acetyl-CoA c-acetyltransferase resulting in the release of CoA acetoacetyl-CoA, The latter compound then reacts with an acetyl-coa through a hydroxymethylglutaryl-CoA synthase resulting in the release of 3-hydroxy-3-methylglutaryl-CoA. The latter compound in turn reacts with a NADPH through a 3-hydroxy-3-methylglutaryl-coenzyme A reductase resulting in the release of a NADP, Coenzyme A and Mevalonic acid. The latter is then phosphorylated by ATP through a mevalonate kinase resulting in the release of ADP and Mevalonic acid-5P which is then phosphorylated by ATP through a phosphomevalonate kinase resulting in the release of ADP and (S)-5-diphosphomevalonic acid. The latter compound in turn reacts with ATP through a diphosphomevalonic decarboxylase resulting in the release of phosphate, ADP, carbon dioxide and Isopentenyl pyrophosphate. The latter compound in turn reacts with isopentenyl diphosphate delta isomerase resulting in the release of dimethylallylpyrophosphate. The latter compound then reacts with isopentenyl pyrophosphate through a farnesyl pyrophosphate synthase resulting in the release of Geranyl-PP. The latter then reacts with an isopentenyl pyrophosphate through farnesyl pyrophosphate synthase resulting in the release of pyrophospate and farnesyl pyrophosphate. Farnesyl pyrophosphate then reacts with NADPH through a squalene synthase in order to produce squalene while also releasing two phosphates and NADP. Squalene then reacts with oxygen and NADPH through a squalene monooxygenase resulting in the release of water, NADP and (S)-2,3-epoxysqualene. The latter in turn reacts with lanosterol synthase resulting in the release of lanosterin. Lanosterin then reacts with oxygen and NADPH through a lanosterol 14-alpha demethylase resulting in the release of formic acid, water, NADP and 4,4-dimethylcholesta-8,14,24-trienol. The latter compound in turn is reduced by an NADPH through a Delta (14)-sterol reductase resulting in the release of NADP and 4,4-dimethyl-5a-cholesta-8,24-dien-3-b-ol. The latter reacts with hydrogen ion,oxygen and NADPH through a methylsterol monooxygenase resulting in the release of NADP, water and 4a-hydroxymethyl-4B-methyl-5a-cholesta-8,24-dien-3B-ol. The latter compound reacts with a hydrogen ion, water, and NADPH through a methylsterol monooxygenase resulting in the release of NADP, water and 4a-formyl-4b-methyl-5a-cholesta-8,24-dien-3B-ol. The latter reacts with oxygen, NADPH through methylsterol monooxygenase resulting in the release of water, NADP and 4B-methyl-4a-carboxy-cholesta-8,24-dien-3B-ol. The latter reacts with an NADP through c-3 sterol dehydrogenase resulting in the release of NADPH, carbon dioxide and 3-keto-4-methylzymosterol. The latter is reduced by NADPH through a 3-keto sterol reductase resulting in the release of NADP and 4a-methylzymosterol. The latter then reacts with hydrogen, oxygen and nadph through methylsterol monooxygenase resulting in the release of water, NADP and 4a-hydroxymethyl-5a-cholesta-8,24-dien-3B-ol. The latter reacts with water, hydrogen and NADPH through a methylsterol monooxygenase resulting in the release of water, NADP and 4a-formyl-5a-cholesta-8,24-dien-3B-ol. The latter reacts with oxygen and NADPH through methylsterol monooxygenase resulting in the release of water, NADP and 4a-carboxy-5a-cholesta-8,24-dien-3B-ol. The latter compound reacts with NADP through a C-3 sterol dehydrogenase resulting in the release of carbon dioxide, NADPH and 5a-cholesta-8,24-dien-3-one. The latter reacts with hydrogen ion and NADPH through a 3-keto sterol reductase resulting in the release of NADP and zymosterol. Zymosterol can either be used to create ergosterol starts with zymosterol reacting with S-adenosylmethionine through a sterol 24-c-methyltransferase resulting in the release of S-adenosylhomocysteine, hydrogen ion and fecosterol. Fecosterol reacts with C-8 sterol isomerase resulting in the release of episterol. Episterol reacts with oxygen, hydrogen ion and ferrocytochrome c through a C-5 sterol desaturase resulting in the release of ferricytochrome c, water and 5,7,24(28)-ergostatrienol. The latter reacts with hydrogen ion, oxygen, NADPH and c-22 sterol desaturase resulting in the release of water, NADP AND ERGOSTA-5,7,22,24(28)-tetraen-3-B-ol. The latter compound reacts with hydrogen ion and NADPH through a C-24 sterol reductase resulting in the release of NADP and ergosterol. Zymosterol reacts with C-8 sterol isomerase resulting in the release of 5a-cholesta-7,24-dien-3b-ol. The latter compound reacts with C-5 sterol desaturase resulting in the release of 7-dehydrodesmosterol. The latter is then converted spontaneously through desmosterol. Desmosterol is then spontaneously turned into cholesterol which can in turn react with Decanoyl-CoA spontaneously resulting in the release of Coenzyme A and CE(10:0).

References

Cholesterol Biosynthesis and Metabolism CE(10:0) References

Bard M, Lees ND, Turi T, Craft D, Cofrin L, Barbuch R, Koegel C, Loper JC: Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase) mutations in Saccharomyces cerevisiae and Candida albicans. Lipids. 1993 Nov;28(11):963-7.

Pubmed: 8277826

Kaneshiro ES: Sterol biosynthesis in Pneumocystis: unique steps that define unique targets. Drug Resist Updat. 2002 Dec;5(6):259-68.

Pubmed: 12531182

Palermo LM, Leak FW, Tove S, Parks LW: Assessment of the essentiality of ERG genes late in ergosterol biosynthesis in Saccharomyces cerevisiae. Curr Genet. 1997 Aug;32(2):93-9.

Pubmed: 9294256

Paltauf, F, Kohlwein, S, Henry, SA. Regulation and compartmentalization of lipid synthesis in yeast. The Molecular and Cellular Biology of the yeast Saccharomyces: Gene Expression. 1992;2:415-500.

Parks LW, Casey WM: Physiological implications of sterol biosynthesis in yeast. Annu Rev Microbiol. 1995;49:95-116. doi: 10.1146/annurev.mi.49.100195.000523.

Pubmed: 8561481

Arthington BA, Hoskins J, Skatrud PL, Bard M: Nucleotide sequence of the gene encoding yeast C-8 sterol isomerase. Gene. 1991 Oct 30;107(1):173-4.

Pubmed: 1743517

Arthington BA, Bennett LG, Skatrud PL, Guynn CJ, Barbuch RJ, Ulbright CE, Bard M: Cloning, disruption and sequence of the gene encoding yeast C-5 sterol desaturase. Gene. 1991 Jun 15;102(1):39-44.

Pubmed: 1864507

Ashman WH, Barbuch RJ, Ulbright CE, Jarrett HW, Bard M: Cloning and disruption of the yeast C-8 sterol isomerase gene. Lipids. 1991 Aug;26(8):628-32.

Pubmed: 1779709

Bard M: Biochemical and genetic aspects of nystatin resistance in saccharomyces cerevisiae. J Bacteriol. 1972 Sep;111(3):649-57.

Pubmed: 4559817

Hata S, Nishino T, Katsuki H, Aoyama Y, Yoshida Y: Two species of cytochrome P-450 involved in ergosterol biosynthesis of yeast. Biochem Biophys Res Commun. 1983 Oct 14;116(1):162-6.

Pubmed: 6357195

He X, Zhang B, Tan H: Overexpression of a sterol C-24(28) reductase increases ergosterol production in Saccharomyces cerevisiae. Biotechnol Lett. 2003 May;25(10):773-8.

Pubmed: 12882006

Kelly SL, Lamb DC, Corran AJ, Baldwin BC, Parks LW, Kelly DE: Purification and reconstitution of activity of Saccharomyces cerevisiae P450 61, a sterol delta 22-desaturase. FEBS Lett. 1995 Dec 18;377(2):217-20.

Pubmed: 8543054

McCammon MT, Hartmann MA, Bottema CD, Parks LW: Sterol methylation in Saccharomyces cerevisiae. J Bacteriol. 1984 Feb;157(2):475-83.

Pubmed: 6363386

Molzahn SW, Woods RA: Polyene resistance and the isolation of sterol mutants in Saccharomyces cerevisiae. J Gen Microbiol. 1972 Sep;72(2):339-48. doi: 10.1099/00221287-72-2-339.

Pubmed: 4562308

Moore JT, Gaylor JL: Isolation and purification of an S-adenosylmethionine: delta 24-sterol methyltransferase from yeast. J Biol Chem. 1969 Dec 10;244(23):6334-40.

Pubmed: 5354959

Leber R, Fuchsbichler S, Klobucnikova V, Schweighofer N, Pitters E, Wohlfarter K, Lederer M, Landl K, Ruckenstuhl C, Hapala I, Turnowsky F: Molecular mechanism of terbinafine resistance in Saccharomyces cerevisiae. Antimicrob Agents Chemother. 2003 Dec;47(12):3890-900.

Pubmed: 14638499

Bard M, Bruner DA, Pierson CA, Lees ND, Biermann B, Frye L, Koegel C, Barbuch R: Cloning and characterization of ERG25, the Saccharomyces cerevisiae gene encoding C-4 sterol methyl oxidase. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):186-90.

Pubmed: 8552601

Crowley JH, Smith SJ, Leak FW, Parks LW: Aerobic isolation of an ERG24 null mutant of Saccharomyces cerevisiae. J Bacteriol. 1996 May;178(10):2991-3.

Pubmed: 8631695

Gachotte D, Barbuch R, Gaylor J, Nickel E, Bard M: Characterization of the Saccharomyces cerevisiae ERG26 gene encoding the C-3 sterol dehydrogenase (C-4 decarboxylase) involved in sterol biosynthesis. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13794-9.

Pubmed: 9811880

Gachotte D, Sen SE, Eckstein J, Barbuch R, Krieger M, Ray BD, Bard M: Characterization of the Saccharomyces cerevisiae ERG27 gene encoding the 3-keto reductase involved in C-4 sterol demethylation. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12655-60.

Pubmed: 10535978

Milla P, Athenstaedt K, Viola F, Oliaro-Bosso S, Kohlwein SD, Daum G, Balliano G: Yeast oxidosqualene cyclase (Erg7p) is a major component of lipid particles. J Biol Chem. 2002 Jan 25;277(4):2406-12. doi: 10.1074/jbc.M104195200. Epub 2001 Nov 12.

Pubmed: 11706015

Hiser L, Basson ME, Rine J: ERG10 from Saccharomyces cerevisiae encodes acetoacetyl-CoA thiolase. J Biol Chem. 1994 Dec 16;269(50):31383-9.

Pubmed: 7989303

Bussey H, Storms RK, Ahmed A, Albermann K, Allen E, Ansorge W, Araujo R, Aparicio A, Barrell B, Badcock K, Benes V, Botstein D, Bowman S, Bruckner M, Carpenter J, Cherry JM, Chung E, Churcher C, Coster F, Davis K, Davis RW, Dietrich FS, Delius H, DiPaolo T, Hani J, et al.: The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI. Nature. 1997 May 29;387(6632 Suppl):103-5.

Pubmed: 9169875

Engel SR, Dietrich FS, Fisk DG, Binkley G, Balakrishnan R, Costanzo MC, Dwight SS, Hitz BC, Karra K, Nash RS, Weng S, Wong ED, Lloyd P, Skrzypek MS, Miyasato SR, Simison M, Cherry JM: The reference genome sequence of Saccharomyces cerevisiae: then and now. G3 (Bethesda). 2014 Mar 20;4(3):389-98. doi: 10.1534/g3.113.008995.

Pubmed: 24374639

Bowman S, Churcher C, Badcock K, Brown D, Chillingworth T, Connor R, Dedman K, Devlin K, Gentles S, Hamlin N, Hunt S, Jagels K, Lye G, Moule S, Odell C, Pearson D, Rajandream M, Rice P, Skelton J, Walsh S, Whitehead S, Barrell B: The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII. Nature. 1997 May 29;387(6632 Suppl):90-3.

Pubmed: 9169872

Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS: Global analysis of protein expression in yeast. Nature. 2003 Oct 16;425(6959):737-41. doi: 10.1038/nature02046.

Pubmed: 14562106

Basson ME, Thorsness M, Finer-Moore J, Stroud RM, Rine J: Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis. Mol Cell Biol. 1988 Sep;8(9):3797-808. doi: 10.1128/mcb.8.9.3797.

Pubmed: 3065625

Johnston M, Hillier L, Riles L, Albermann K, Andre B, Ansorge W, Benes V, Bruckner M, Delius H, Dubois E, Dusterhoft A, Entian KD, Floeth M, Goffeau A, Hebling U, Heumann K, Heuss-Neitzel D, Hilbert H, Hilger F, Kleine K, Kotter P, Louis EJ, Messenguy F, Mewes HW, Hoheisel JD, et al.: The nucleotide sequence of Saccharomyces cerevisiae chromosome XII. Nature. 1997 May 29;387(6632 Suppl):87-90.

Pubmed: 9169871

Oulmouden A, Karst F: Nucleotide sequence of the ERG12 gene of Saccharomyces cerevisiae encoding mevalonate kinase. Curr Genet. 1991 Jan;19(1):9-14.

Pubmed: 1645230

Kearsey SE, Edwards J: Mutations that increase the mitotic stability of minichromosomes in yeast: characterization of RAR1. Mol Gen Genet. 1987 Dec;210(3):509-17. doi: 10.1007/bf00327205.

Pubmed: 3323847

Tsay YH, Robinson GW: Cloning and characterization of ERG8, an essential gene of Saccharomyces cerevisiae that encodes phosphomevalonate kinase. Mol Cell Biol. 1991 Feb;11(2):620-31. doi: 10.1128/mcb.11.2.620.

Pubmed: 1846667

Toth MJ, Huwyler L: Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase. J Biol Chem. 1996 Apr 5;271(14):7895-8. doi: 10.1074/jbc.271.14.7895.

Pubmed: 8626466

Berges T, Guyonnet D, Karst F: The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase is essential for viability, and a single Leu-to-Pro mutation in a conserved sequence leads to thermosensitivity. J Bacteriol. 1997 Aug;179(15):4664-70. doi: 10.1128/jb.179.15.4664-4670.1997.

Pubmed: 9244250

Philippsen P, Kleine K, Pohlmann R, Dusterhoft A, Hamberg K, Hegemann JH, Obermaier B, Urrestarazu LA, Aert R, Albermann K, Altmann R, Andre B, Baladron V, Ballesta JP, Becam AM, Beinhauer J, Boskovic J, Buitrago MJ, Bussereau F, Coster F, Crouzet M, D'Angelo M, Dal Pero F, De Antoni A, Del Rey F, Doignon F, Domdey H, Dubois E, Fiedler T, Fleig U, Floeth M, Fritz C, Gaillardin C, Garcia-Cantalejo JM, Glansdorff NN, Goffeau A, Gueldener U, Herbert C, Heumann K, Heuss-Neitzel D, Hilbert H, Hinni K, Iraqui Houssaini I, Jacquet M, Jimenez A, Jonniaux JL, Karpfinger L, Lanfranchi G, Lepingle A, Levesque H, Lyck R, Maftahi M, Mallet L, Maurer KC, Messenguy F, Mewes HW, Mosti D, Nasr F, Nicaud JM, Niedenthal RK, Pandolfo D, Pierard A, Piravandi E, Planta RJ, Pohl TM, Purnelle B, Rebischung C, Remacha M, Revuelta JL, Rinke M, Saiz JE, Sartorello F, Scherens B, Sen-Gupta M, Soler-Mira A, Urbanus JH, Valle G, Van Dyck L, Verhasselt P, Vierendeels F, Vissers S, Voet M, Volckaert G, Wach A, Wambutt R, Wedler H, Zollner A, Hani J: The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications. Nature. 1997 May 29;387(6632 Suppl):93-8.

Pubmed: 9169873

Anderson MS, Muehlbacher M, Street IP, Proffitt J, Poulter CD: Isopentenyl diphosphate:dimethylallyl diphosphate isomerase. An improved purification of the enzyme and isolation of the gene from Saccharomyces cerevisiae. J Biol Chem. 1989 Nov 15;264(32):19169-75.

Pubmed: 2681212

Anderson MS, Yarger JG, Burck CL, Poulter CD: Farnesyl diphosphate synthetase. Molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae. J Biol Chem. 1989 Nov 15;264(32):19176-84.

Pubmed: 2681213

Galibert F, Alexandraki D, Baur A, Boles E, Chalwatzis N, Chuat JC, Coster F, Cziepluch C, De Haan M, Domdey H, Durand P, Entian KD, Gatius M, Goffeau A, Grivell LA, Hennemann A, Herbert CJ, Heumann K, Hilger F, Hollenberg CP, Huang ME, Jacq C, Jauniaux JC, Katsoulou C, Karpfinger-Hartl L, et al.: Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X. EMBO J. 1996 May 1;15(9):2031-49.

Pubmed: 8641269

This pathway was generated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.

Generated from SMP0070041

Highlighted elements will appear in red.

Highlight Compounds

	4α-carboxy-5α-cholesta-8,24-dien-3β-ol
	4α-formyl-4β-methyl-5α-cholesta-8,24-dien-3β-ol
	4β-methyl-4α-carboxy-cholesta-8,24-dien-3β-ol
	ergosta-5,7,22,24(28)-tetraen-3-β-ol
	(R)-5-Diphosphomevalonic acid
	(S)-2,3-Epoxysqualene
	3-Hydroxy-3-methylglutaryl-CoA
	3-Keto-4-methylzymosterol
	4,4-Dimethyl-5a-cholesta-8,24-dien-3-b-ol
	4,4-Dimethylcholesta-8,14,24-trienol
	4a-Methylzymosterol
	4α-formyl-5α-cholesta-8,24-dien-3β-ol
	4α-hydroxymethyl-4β-methyl-5α-cholesta-8,24-dien-3β-ol
	4α-hydroxymethyl-5α-cholesta-8,24-dien-3β-ol
	5,7,24(28)-Ergostatrienol
	5α-cholesta-8,24-dien-3-one
	7-dehydrodesmosterol
	7-Dehydrodesmosterol
	Acetoacetyl-CoA
	Acetyl-CoA
	Adenosine diphosphate
	Adenosine triphosphate
	Carbon dioxide
	CE(10:0)
	Cholesterol
	Coenzyme A
	Decanoyl-CoA
	Desmosterol
	Dimethylallylpyrophosphate
	Episterol
	Ergosterol
	Farnesyl pyrophosphate
	fecosterol
	ferricytochrome c
	ferrocytochrome c
	Formic acid
	Geranyl-PP
	Hydrogen Ion
	Isopentenyl pyrophosphate
	Lanosterol
	Mevalonic acid
	Mevalonic acid-5P
	NADP
	NADPH
	Oxygen
	Phosphate
	Pyrophosphate
	S-Adenosylhomocysteine
	S-Adenosylmethionine
	Squalene
	Water
	Zymosterol

Highlight Proteins

	3-hydroxy-3-methylglutaryl-coenzyme A reductase 1
	3-hydroxy-3-methylglutaryl-coenzyme A reductase 2
	3-keto sterol reductase
	Acetyl-CoA acetyltransferase
	C-22 sterol desaturase
	C-24 sterol reductase
	C-3 sterol dehydrogenase
	C-5 sterol desaturase
	C-8 sterol isomerase
	Delta(14)-sterol reductase
	Diphosphomevalonate decarboxylase
	Farnesyl pyrophosphate synthase
	Hydroxymethylglutaryl-CoA synthase
	Isopentenyl-diphosphate Delta-isomerase
	Lanosterol 14-alpha demethylase
	Lanosterol synthase
	Methylsterol monooxygenase
	mevalonate kinase
	Phosphomevalonate kinase
	squalene monooxygenase
	Squalene synthase
	Sterol 24-C-methyltransferase

Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.

Visualize Compound Data

		4α-carboxy-5α-cholesta-8,24-dien-3β-ol
		4α-formyl-4β-methyl-5α-cholesta-8,24-dien-3β-ol
		4β-methyl-4α-carboxy-cholesta-8,24-dien-3β-ol
		ergosta-5,7,22,24(28)-tetraen-3-β-ol
		(R)-5-Diphosphomevalonic acid
		(S)-2,3-Epoxysqualene
		3-Hydroxy-3-methylglutaryl-CoA
		3-Keto-4-methylzymosterol
		4,4-Dimethyl-5a-cholesta-8,24-dien-3-b-ol
		4,4-Dimethylcholesta-8,14,24-trienol
		4a-Methylzymosterol
		4α-formyl-5α-cholesta-8,24-dien-3β-ol
		4α-hydroxymethyl-4β-methyl-5α-cholesta-8,24-dien-3β-ol
		4α-hydroxymethyl-5α-cholesta-8,24-dien-3β-ol
		5,7,24(28)-Ergostatrienol
		5α-cholesta-8,24-dien-3-one
		7-dehydrodesmosterol
		7-Dehydrodesmosterol
		Acetoacetyl-CoA
		Acetyl-CoA
		Adenosine diphosphate
		Adenosine triphosphate
		Carbon dioxide
		CE(10:0)
		Cholesterol
		Coenzyme A
		Decanoyl-CoA
		Desmosterol
		Dimethylallylpyrophosphate
		Episterol
		Ergosterol
		Farnesyl pyrophosphate
		fecosterol
		ferricytochrome c
		ferrocytochrome c
		Formic acid
		Geranyl-PP
		Hydrogen Ion
		Isopentenyl pyrophosphate
		Lanosterol
		Mevalonic acid
		Mevalonic acid-5P
		NADP
		NADPH
		Oxygen
		Phosphate
		Pyrophosphate
		S-Adenosylhomocysteine
		S-Adenosylmethionine
		Squalene
		Water
		Zymosterol

Visualize Protein Data

		3-hydroxy-3-methylglutaryl-coenzyme A reductase 1
		3-hydroxy-3-methylglutaryl-coenzyme A reductase 2
		3-keto sterol reductase
		Acetyl-CoA acetyltransferase
		C-22 sterol desaturase
		C-24 sterol reductase
		C-3 sterol dehydrogenase
		C-5 sterol desaturase
		C-8 sterol isomerase
		Delta(14)-sterol reductase
		Diphosphomevalonate decarboxylase
		Farnesyl pyrophosphate synthase
		Hydroxymethylglutaryl-CoA synthase
		Isopentenyl-diphosphate Delta-isomerase
		Lanosterol 14-alpha demethylase
		Lanosterol synthase
		Methylsterol monooxygenase
		mevalonate kinase
		Phosphomevalonate kinase
		squalene monooxygenase
		Squalene synthase
		Sterol 24-C-methyltransferase

Downloads

SVG Image

Simple SVG Image

Large Font SVG Image

Simple Large Font SVG Image

Greyscale SVG Image

BioPAX

SBGN

SBML

PWML

PNG Image

All files (.zip)

Settings