Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Steroid Biosynthesis
Homo sapiens
Metabolic Pathway
Created: 2013-08-01
Last Updated: 2025-01-28
The steroid biosynthesis (or cholesterol biosynthesis) pathway is an anabolic metabolic pathway that produces steroids from simple precursors. It starts with the mevalonate pathway, where acetyl-CoA and acetoacetyl-CoA are the first two building blocks. These compounds are joined together via the enzyme hydroxy-3-methylgutaryl (HMG)-CoA synthase to produce the compound known as hydroxy-3-methylgutaryl-CoA (HMG-CoA). This compound is then reduced to mevalonic acid via the enzyme HMG-CoA reductase. It is important to note that HMG-CoA reductase is the protein target of many cholesterol-lowering drugs called statins (PMID: 12602122). The resulting mevalonic acid (or mevalonate) is then phosphorylated by the enzyme known as mevalonate kinase to form mevalonate-5-phosphate, which is then phosphorylated again by phosphomevalonate kinase to form mevolonate-5-pyrophsophate. This pyrophosphorylated compound is subsequently decarboxylated via the enzyme mevolonate-5-pyrophsophate decarboxylase to form isopentylpyrophosphate (IPP). IPP can also be isomerized (via isopentenyl-PP-isomerase) to form dimethylallylpyrophosphate (DMAPP). IPP and DMAPP can both donate isoprene units, which can then be joined together to make farnesyl and geranylgeranyl intermediates. Specifically, three molecules of IPP condense to form farnesyl pyrophosphate through the action of the enzyme known as geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form a molecule known as squalene by the action of the enzyme known as squalene synthase in the cell’s endoplasmic reticulum. The enzyme oxidosqualene cyclase then cyclizes squalene to form lanosterol. Lanosterol is a tetracyclic triterpenoid, and serves as the framework from which all steroids are derived. 14-Demethylation of lanosterol by a cytochrome P450 enzyme known as CYP51 eventually yields cholesterol. Cholesterol is the central steroid in human biology. It can be obtained from animal fats consumed in the diet or synthesized de novo (as described above). Cholesterol is an essential constituent of lipid bilayer membranes (where it forms cholesterol esters) and is the starting point for the biosynthesis of steroid hormones, bile acids and bile salts, and vitamin D. Steroid hormones are mostly synthesized in the adrenal gland and gonads. They regulate energy metabolism and stress responses (via glucocorticoids such as cortisol), salt balance (mineralocorticoids such as aldosterone), and sexual development and function (via androgens such as testosterone and estrogens such as estradiol). Bile acids and bile salts (such as taurocholate) are mostly synthesized in the liver. They are released into the intestine and function as detergents to solubilize dietary fats. Cholesterol is the main constituent of atheromas. These are the fatty lumps found in the walls of arteries that occur in atherosclerosis and, when ruptured, can cause heart attacks.
References
Steroid Biosynthesis References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.)Â (2005). New York: W.H Freeman.
Norman, A.W, and Litwack, G. Hormones (2nd ed.) (1997) San Diego : Academic Press.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Simons J: The $10 billion pill. Fortune. 2003 Jan 20;147(1):58-62, 66, 68.
Pubmed: 12602122
Song XQ, Fukao T, Yamaguchi S, Miyazawa S, Hashimoto T, Orii T: Molecular cloning and nucleotide sequence of complementary DNA for human hepatic cytosolic acetoacetyl-coenzyme A thiolase. Biochem Biophys Res Commun. 1994 May 30;201(1):478-85. doi: 10.1006/bbrc.1994.1726.
Pubmed: 7911016
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. doi: 10.1038/nature02055.
Pubmed: 14574404
Russ AP, Ruzicka V, Maerz W, Appelhans H, Gross W: Amplification and direct sequencing of a cDNA encoding human cytosolic 3-hydroxy-3-methylglutaryl-coenzyme A synthase. Biochim Biophys Acta. 1992 Oct 20;1132(3):329-31. doi: 10.1016/0167-4781(92)90172-v.
Pubmed: 1358203
Rokosz LL, Boulton DA, Butkiewicz EA, Sanyal G, Cueto MA, Lachance PA, Hermes JD: Human cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase: expression, purification, and characterization of recombinant wild-type and Cys129 mutant enzymes. Arch Biochem Biophys. 1994 Jul;312(1):1-13. doi: 10.1006/abbi.1994.1273.
Pubmed: 7913309
Houten SM, Koster J, Romeijn GJ, Frenkel J, Di Rocco M, Caruso U, Landrieu P, Kelley RI, Kuis W, Poll-The BT, Gibson KM, Wanders RJ, Waterham HR: Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. Eur J Hum Genet. 2001 Apr;9(4):253-9. doi: 10.1038/sj.ejhg.5200595.
Pubmed: 11313768
Hogenboom S, Tuyp JJ, Espeel M, Koster J, Wanders RJ, Waterham HR: Mevalonate kinase is a cytosolic enzyme in humans. J Cell Sci. 2004 Feb 1;117(Pt 4):631-9. doi: 10.1242/jcs.00910.
Pubmed: 14730012
Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT: Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet. 1999 Jun;22(2):175-7. doi: 10.1038/9691.
Pubmed: 10369261
Chambliss KL, Slaughter CA, Schreiner R, Hoffmann GF, Gibson KM: Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence. J Biol Chem. 1996 Jul 19;271(29):17330-4. doi: 10.1074/jbc.271.29.17330.
Pubmed: 8663599
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Olivier LM, Chambliss KL, Gibson KM, Krisans SK: Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting. J Lipid Res. 1999 Apr;40(4):672-9.
Pubmed: 10191291
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
Hinson DD, Chambliss KL, Toth MJ, Tanaka RD, Gibson KM: Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways. J Lipid Res. 1997 Nov;38(11):2216-23.
Pubmed: 9392419
Xuan JW, Kowalski J, Chambers AF, Denhardt DT: A human promyelocyte mRNA transiently induced by TPA is homologous to yeast IPP isomerase. Genomics. 1994 Mar 1;20(1):129-31. doi: 10.1006/geno.1994.1139.
Pubmed: 8020941
Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. doi: 10.1038/nature02462.
Pubmed: 15164054
Wilkin DJ, Kutsunai SY, Edwards PA: Isolation and sequence of the human farnesyl pyrophosphate synthetase cDNA. Coordinate regulation of the mRNAs for farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 3-hydroxy-3-methylglutaryl coenzyme A synthase by phorbol ester. J Biol Chem. 1990 Mar 15;265(8):4607-14.
Pubmed: 1968462
Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S: Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1. DNA Res. 1994;1(1):27-35. doi: 10.1093/dnares/1.1.27.
Pubmed: 7584026
Kainou T, Kawamura K, Tanaka K, Matsuda H, Kawamukai M: Identification of the GGPS1 genes encoding geranylgeranyl diphosphate synthases from mouse and human. Biochim Biophys Acta. 1999 Mar 25;1437(3):333-40. doi: 10.1016/s1388-1981(99)00028-1.
Pubmed: 10101267
Ericsson J, Greene JM, Carter KC, Shell BK, Duan DR, Florence C, Edwards PA: Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression. J Lipid Res. 1998 Sep;39(9):1731-9.
Pubmed: 9741684
Kuzuguchi T, Morita Y, Sagami I, Sagami H, Ogura K: Human geranylgeranyl diphosphate synthase. cDNA cloning and expression. J Biol Chem. 1999 Feb 26;274(9):5888-94. doi: 10.1074/jbc.274.9.5888.
Pubmed: 10026212
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
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
Visualize Protein Data
Downloads
Settings