IUPAC-recommended ring-lettering (left) and atom-numbering (right) of cholestane, a prototypical steroid skeleton.^[1] The four rings A-D form the gonane nucleus of the steroid.

Stick model of the steroid lanosterol. The total number of carbons (30) reflects its triterpenoid origin.

A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone. The core of steroids is composed of twenty carbon atoms bonded together that take the form of four fused rings: three cyclohexane rings (designated as rings A, B, and C in the figure to the right) and one cyclopentane ring (the D ring). The steroids vary by the functional groups attached to this four-ring core and by the oxidation state of the rings. Sterols are special forms of steroids, with a hydroxyl group at position-3 and a skeleton derived from cholestane.^[1]

Hundreds of distinct steroids are found in plants, animals, and fungi. All steroids are made in cells either from the sterols lanosterol (animals and fungi) or from cycloartenol (plants). Both lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.^[2]

Structure[link]

Steroids are a class of organic compounds with a chemical structure that contains the core of gonane or a skeleton derived therefrom. Usually, methyl groups are present at the carbons C-10 and C-13. At carbon C-17 an alkyl side chain may also be present.

The basic skeleton of a steroid, with standard stereo orientations. R is a side-chain.

Cholestane, a typical steroid

Numbering of carbon atoms in gonane

Gonane is the simplest possible steroid and is composed of seventeen carbon atoms, bonded together to form four fused rings. The three cyclohexane rings (designated as rings A, B, and C in the figure above right) form the skeleton of phenanthrene; ring D has a cyclopentane structure. Hence, together they are called cyclopentaphenanthrene.^[3]

Commonly, steroids have a methyl group at the carbons C-10 and C-13 and an alkyl side chain at carbon C-17. Further, they vary by the configuration of the side chain, the number of additional methyl groups and the functional groups attached to the rings. For example the hydroxyl group at position C-3 in sterols.

Cholesterol

Cholic acid

Medrogestone

Classification[link]

Taxonomical/Functional[link]

Some of the common categories of steroids:

• Animal
  • Insect
    • Ecdysteroids such as ecdysterone
  • Vertebrate
    • Steroid hormones
      • Sex steroids are a subset of sex hormones that produce sex differences or support reproduction. They include androgens, estrogens, and progestagens.
      • Corticosteroids include glucocorticoids and mineralocorticoids. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Most medical 'steroid' drugs are corticosteroids.
      • Anabolic steroids are a class of steroids that interact with androgen receptors to increase muscle and bone synthesis. There are natural and synthetic anabolic steroids. In popular language, the word "steroids" usually refers to anabolic steroids.
    • Cholesterol, which modulates the fluidity of cell membranes and is the principal constituent of the plaques implicated in atherosclerosis.
• Plant
  • Phytosterols
  • Brassinosteroids
• Fungus
  • Ergosterols

Structural[link]

It is also possible to classify steroids based upon their chemical composition. One example of how MeSH performs this classification is available at the Wikipedia MeSH catalog. Examples from this classification include:

Gonane (or steroid nucleus) is the parent (17-carbon tetracyclic) hydrocarbon molecule without any alkyl sidechains.^[4]

Biosynthesis[link]

Simplified version of latter part of steroid synthesis pathway, where the intermediates isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) form geranyl pyrophosphate (GPP), squalene and, finally, lanosterol, the first steroid in the pathways. Some intermediates are omitted for clarity.

Steroid biosynthesis is an anabolic metabolic pathway that produces steroids from simple precursors. A unique biosynthetic pathway is followed in animals compared to many other organisms, making the pathway a common target for antibiotics and other anti-infective drugs. In addition, steroid metabolism in humans is the target of cholesterol-lowering drugs such as statins.

In humans and other animals, the biosynthesis of steroids follows the mevalonate pathway that uses acetyl-CoA as building-blocks to form dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP).^[5] In subsequent steps, DMAPP and IPP are joined to form geranyl pyrophosphate (GPP), which in turn is used to synthesize the steroid lanosterol. Further modifications of lanosterol into other steroids are classified steroidogenesis transformations.

Mevalonate pathway[link]

Mevalonate pathway

The mevalonate pathway or HMG-CoA reductase pathway starts with and ends with dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP).

Pharmacology[link]

A number of drugs target the mevalonate pathway:

• Statins (used for elevated cholesterol levels)
• Bisphosphonates (used in treatment of various bone-degenerative diseases)

DMAPP to lanosterol[link]

Isopentenyl pyrophosphate and dimethylallyl pyrophosphate donate isoprene units, which are assembled and modified to form terpenes and isoprenoids,^[6] which are a large class of lipids that include the carotenoids, and form the largest class of plant natural products.^[7]

Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol.^[8] Lanosterol can then be converted into other steroids such as cholesterol and ergosterol.^[8][9]

Human Steroidogenesis

Steroidogenesis[link]

Steroidogenesis is the biological process by which steroids are generated from cholesterol and transformed into other steroids. The pathways of steroidogenesis differ between different species, but the pathways of human steroidogenesis are shown in the figure.

Products of steroidogenesis include:

• androgens
  • testosterone
• estrogens and progesterone
• corticoids
  • cortisol
  • aldosterone

Steroids include estrogen, cortisol, progesterone, and testosterone. Estrogen and progesterone are made primarily in the ovary and in the placenta during pregnancy, and testosterone in the testes. Testosterone is also converted into estrogen to regulate the supply of each, in the bodies of both females and males. Certain neurons and glia in the central nervous system (CNS) express the enzymes that are required for the local synthesis of pregnane neurosteroids, either de novo or from peripherally-derived sources. The rate-limiting step of steroid synthesis is the conversion of cholesterol to pregnenolone, which occurs inside the mitochondrion.^[10]

Regulation[link]

Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.

Alternative pathways[link]

In plants and bacteria, the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates.^[11][6]

Metabolism[link]

Steroids are oxidized mainly by cytochrome P450 oxidase enzymes, such as CYP3A4. These reactions introduce oxygen into the steroid ring and allows the structure to be broken up by other enzymes, to form bile acids as final products.^[12] These bile acids can then be eliminated through secretion from the liver in the bile.^[13] The expression of this oxidase gene can be upregulated by the steroid sensor PXR when there is a high blood concentration of steroids.^[14]

Use[link]

Medical use[link]

Misuse[link]

See also[link]

pharmacology portal

• Batrachotoxin
• List of steroid abbreviations
• Steroid hormone
• Corticosteroid
• Sex steroid
• Steroid sulfatase
• Steroid hydroxylases
• Steroidogenic acute regulatory protein

References[link]

External links[link]

• Nomenclature of Steroids Home Page at Queen Mary University of London.
• The Science of Steroids (Documentary)
• Steroidogenesis

David Ortiz
Ortiz pointing to the sky after hitting a home run
Boston Red Sox – No. 34
Designated hitter / First baseman
Born: (1975-11-18) November 18, 1975 (age 36) Santo Domingo, Dominican Republic
Bats: Left	Throws: Left
MLB debut
September 24, 1997 for the Minnesota Twins
Career statistics (through June 1, 2012)
Batting average	.285
Home runs	391
Hits	1,823
Runs batted in	1,303
Teams
Minnesota Twins (1997–2002) Boston Red Sox (2003–present)
Career highlights and awards
The Sporting News Designated Hitter of the Decade (2009) Sports Illustrated MLB All-Decade Team (2009) 2× World Series champion (2004, 2007) ALCS MVP (2004) 7× All-Star (2004, 2005, 2006, 2007, 2008, 2010, 2011) 5× Silver Slugger Award (2004, 2005, 2006, 2007, 2011) Hank Aaron Award (2005) 6× Edgar Martínez Award (2003–2007, 2011) AL home run leader (2006) AL RBI leader (2005, 2006) MLB record for home runs by DH (345) MLB record for RBI by DH (1,131) Home Run Derby winner (2010) Roberto Clemente Award (2011)

David Américo Ortiz Arias (born November 18, 1975), nicknamed "Big Papi", is a Dominican-American professional baseball player with the Boston Red Sox of Major League Baseball. Previously, Ortiz played with the Minnesota Twins from 1997 until 2002. Ortiz is a seven-time All-Star and holds the Red Sox single season record for home runs in a regular season with 54, set during the 2006 season. In 2005, Red Sox ownership presented him with a plaque proclaiming Ortiz "the greatest clutch-hitter in the history of the Boston Red Sox".^[1][2]

Early career[link]

Seattle Mariners and Minnesota Twins (1992–2002)[link]

Ortiz shares a word with Toby Hall, then of the Tampa Bay Devil Rays.

Ortiz graduated from Estudia Espallat High School in the Dominican Republic and in 1992 he was signed by the Seattle Mariners who listed him as "David Arias". He played for the Wisconsin Timber Rattlers, a Mariners farm team, until 1996, when he was traded to the Minnesota Twins as the player to be named later in an earlier trade for Dave Hollins. When he arrived in Minnesota, he informed the team that he preferred to be listed as "David Ortiz."

He made his Twins debut in September 1997. For a few years, he was moved back and forth between the Twins and their minor league affiliate in Connecticut, the New Britain Rock Cats. The Twins advanced to the American League Championship Series that year, where they lost to the Anaheim Angels. Despite showing flashes of talent, Ortiz's time with the Twins will be remembered as a series of injuries and inconsistency both in the field and at the plate. Ortiz suffered wrist injuries in both 1998 and 2001. He continued to experience knee problems in early 2002 that plagued him throughout the season, despite hitting 32 doubles, 20 home runs and 75 RBIs in 125 games. He was released by the Twins after the season. In six seasons with the Twins, Ortiz hit 58 home runs and 238 RBI.^[3]

Boston Red Sox (2003–Present)[link]

2003[link]

On January 22, Ortiz signed a free agent contract with the Boston Red Sox. He played sparingly in the first two months of the season, primarily pinch hitting and starting occasionally as a DH. On June 1, manager Grady Little benched Jeremy Giambi and inserted Ortiz in the starting lineup as the full time DH. In July Ortiz hit 8 home runs, and in August he had 11. He finished the season batting .288 with 31 home runs and 101 RBI. He finished 5th in the American League MVP voting.

In the postseason he struggled in the ALDS against the Oakland A's until Game 4 when he hit a 2 run double in the bottom of the 8th inning off of closer Keith Foulke to give the Red Sox the lead. In the ALCS against the New York Yankees, Ortiz had 2 home runs and 6 RBI as Boston lost in 7 games.

2004[link]

Ortiz was a major force in leading the Red Sox to their first World Series title in 86 years and ending the Curse of the Bambino. During the regular season, Ortiz hit 41 home runs and had 139 RBI while batting .301 with an OPS of .983. He finished 2nd in the American League in both home runs and RBI. He was voted onto the All-Star team for the first time in his career. He finished 4th in American League MVP voting.

In the playoffs, Ortiz hit .409 with 5 home runs and 23 RBI. He had multiple game-winning hits to help Boston advance to and ultimately win the World Series. He hit a walk-off home run off of Jarrod Washburn to win the American League Division Series against the Angels. He then hit a walk-off home run against the New York Yankees in Game 4 of the ALCS and a walk-off single in Game 5 during the American League Championship Series. His post-season heroics earned him MVP honors for the ALCS, the first time a DH had ever been named MVP.

On May 28, Ortiz hit his 100th career home run, a grand slam, off of Joel Pineiro of the Seattle Mariners at Fenway Park.

Ortiz was suspended for 3 games after being ejected following an incident on July 16 in a game against the Angels in which he threw several bats onto the field that came close to hitting umpires Bill Hohn and Mark Carlson.

2005[link]

Ortiz hit 47 home runs and had 148 RBI while batting .300 with an OPS of 1.001. He led the American League in RBI finished 2nd in home runs and 3rd in OPS. He finished 2nd in the American League MVP voting while leading the Red Sox to their 3rd consecutive playoff appearance.

2006[link]

Ortiz hit 54 home runs (setting a new Red Sox record) and had 137 RBI, while batting .287 with an OPS of 1.049. He led the American League in both home runs and RBI, winning the home run crown by 10 over the 2nd-place finisher Jermaine Dye. He finished 3rd in the American League MVP voting.

On June 29, Ortiz hit his 200th career home run against Duaner Sanchez of the New York Mets at Fenway Park.

On September 20, Ortiz tied Jimmie Foxx's single season Red Sox home run record of 50 set in 1938; in the 6th inning against Minnesota Twins starting pitcher Boof Bonser.

On September 21, Ortiz broke Foxx's single season Red Sox home run record by hitting his 51st home run off his former teammate, Johan Santana of the Minnesota Twins. The home run came on a 1–0 pitch in the first inning and it was his 44th home run of the season as a designated hitter, breaking his own American League single-season record.

Health scare[link]

Ortiz said he began feeling ill between games of a day-night doubleheader on August 18, 2006, against New York. Between games, he had gone home and tried to sleep but could not. Ortiz was reportedly driven to the hospital by a team assistant. An irregular heartbeat was the cause for the stress according to his doctors. Ortiz would not originally talk about his condition, but opened up to the media on August 25, reportedly saying "I'm a healthy son of a [gun]."^[4]

On August 28, Ortiz had recurring symptoms from his irregular heartbeat and was a last minute scratch in the Red Sox game at Oakland. Manager Terry Francona and General Manager Theo Epstein agreed that Ortiz fly back to Boston where he was reevaluated and cleared to play again in early September.

2007[link]

Ortiz once again played a major role as he helped lead the Red Sox to their seventh World Series title. Despite playing the entire season with a torn meniscus in his right knee as well as nagging injuries to his shoulder and quadriceps, he finished the year hitting .332 with 35 home runs and 117 RBI. In addition, he hit 52 doubles, led the American League in extra base hits and had an OPS of 1.066.

In the postseason Ortiz batted .370 with 3 home runs and 10 RBI.

2008[link]

Ortiz started slowly after suffering a wrist injury which caused him to miss several weeks. He played in only 109 games and finished the season hitting .264 with just 23 home runs and 89 RBI, his lowest totals since joining the Red Sox.

Ortiz at bat in 2009

2009[link]

Ortiz struggled early in the season, hitting only .206 with no home runs and 30 strikeouts in his first 34 games. On May 22, Ortiz hit his first home run of the season off Brett Cecil of the Toronto Blue Jays, ending his career-high 178 homerless at-bat streak.^[5] In June, Ortiz broke out of his slump by hitting 8 home runs with 22 RBIs. Ortiz had 9 home runs in both July and August.

On July 9, Ortiz hit his 300th career home run against Luke Hochevar of the Kansas City Royals at Fenway Park.

On September 17, Ortiz hit his 270th career home run as a DH off of Jose Arredondo of the Los Angeles Angels breaking the all time record held by Frank Thomas.

Ortiz finished the season with 28 home runs and 99 RBI.

2010[link]

Ortiz hit .270 with 32 home runs and 102 RBI. He also won the Home Run Derby.

2011[link]

On April 2, Ortiz set the record for RBI by a designated hitter with 1,004 passing Edgar Martinez.

On May 21, Ortiz became only the fifth player to hit 300 home runs as a member of the Red Sox, joining Ted Williams, Carl Yastrzemski, Jim Rice, and Dwight Evans.

On July 8, during a game against the Baltimore Orioles, three pitches were thrown inside close to Ortiz by Kevin Gregg. Ortiz took exception of the third ball that was close to him. Warnings were issued to both dugouts. When Ortiz popped out on the 3-0 count, Kevin Gregg taunted Ortiz and was ejected. Ortiz charged at Gregg and started a bench-clearing brawl. Both players were ejected for the incident and were each sentenced to a four game suspension.

Ortiz finished the season hitting .309 with 29 home runs and 96 RBI.

On October 20, Major League Baseball announced that Ortiz was the winner of the Roberto Clemente Award.

Performance-enhancing drug positive test result in 2003[link]

On July 30, 2009, The New York Times reported that Ortiz and then-teammate Manny Ramirez were among a group of roughly 100 major league players to test positive for performance-enhancing drugs during 2003 survey testing.^[6] Five months before the Times allegations surfaced, Ortiz stated in an interview that players who tested positive for steroids should be suspended for an entire season.^[6] Before the Red Sox's game that afternoon, Ortiz declined to comment on the report, saying, "I'm not talking about that anymore."^[6] Afterwards, he confirmed he had tested positive and promised to speak with the media once he "[got] to the bottom of" the matter.^[7]

Ten days later, Ortiz held a press conference before a game at Yankee Stadium and denied ever buying or using steroids but suggested the positive test might have been due to his use of supplements and vitamins at the time.^[8] When asked which supplements he had been taking, Ortiz said he did not know.^[9] Ortiz was accompanied at the press conference by the general counsel of the players union, Michael Weiner. Because the list of players who tested positive was seized as part of a government investigation and is currently under court-ordered seal pending the outcome of litigation, Weiner said the players union was unable to provide Ortiz with any details about his test result, including what substance he tested positive for.

Personal life[link]

Each time Ortiz crosses the plate after hitting a home run, he looks up and points both index fingers to the sky in tribute to his mother Angela Rosa Arias, who died in a car crash in January 2002 at the age of 46.^[10] Ortiz also has a tattoo of his mother on his biceps.

Ortiz and his wife Tiffany have three children. Since marrying Tiffany, he has become a fan of the Green Bay Packers (his wife hails from Kaukauna, Wisconsin, a town in between the cities of Green Bay and Appleton).^[11]

On June 11, 2008, Ortiz became a United States citizen at John F. Kennedy Library in Boston.^[12][13]

Reebok sponsorship[link]

In April 2007, sporting goods company Reebok debuted the Big Papi 10M Mid Baseball cleat at a party in Canton, Massachusetts, home to the headquarters of Reebok International Ltd. At the party, Ortiz was quoted as saying, "Reebok's loyalty and friendship have always made me feel right at home and we are true partners in every sense of the word,... ." Ortiz first used the cleat during the 2007 MLB All Star Game in San Francisco, California.^[14]

Charity work[link]

The David Ortiz Children's Fund was founded in 2007 to support a range of causes that Ortiz believes in. The Fund allows Ortiz the flexibility to donate to those children are in the most need at any given time, from Boston to the Dominican Republic and beyond. Ortiz released his own Charity Wine label in 2008 with all the proceeds going to the David Ortiz Children's Fund. The wine called Vintage Papi proceeded to raise $150,000 for charity.^[15]

Trademark fight with Jay-Z[link]

In April 2010, rapper and producer Jay-Z and his business partner Juan Perez initiated a trademark infringement case against Big Papi's night club 40/40 located in his native Dominican Republic. The suit claimed that Big Papi's night club name was chosen to take advantage of the fame of the record producers chain of sports clubs. The term 40/40 in baseball refers to the roughly 2 score ballplayers in the Major Leagues who have both 40 home runs and 40 stolen bases in a single season.http://latimesblogs.latimes.com/gossip/2010/04/jayz-sures-red-sox-big-papi-david-ortiz-4040-club-name.html

Career highlights[link]

• The Sporting News Designated Hitter of the Decade (2009)
• Sports Illustrated MLB All-Decade Team (2009)
• Member of the 2004 Boston Red Sox team that won the World Series.
• Member of the 2007 Boston Red Sox team that won the World Series.
• American League Championship Series MVP (2004)
• 7-time All-Star (2004–2008, 2010–2011)
• 2005 Hank Aaron Award winner
• 6-time winner of the Edgar Martínez Award (2003–2007. 2011)
• 5-time winner of the Silver Slugger Award (2004–2007, 2011)
• Top 5 MVP vote-receiver five times (5th, 2003; 4th, 2004; 2nd, 2005; 3rd, 2006; 4th, 2007)
• Led the American League in extra base hits 3 times (2004, 2005, 2007)
• Led the American League in Home Runs (2006)
• Led the American League in Runs Batted In (2005, 2006)
• American League Player of the Month for September 2005, July 2006, and May 2010.
• Red Sox single-season home-run leader (54; 2006)
• Tied with Babe Ruth for AL single-season home-run record in road games (32; 2006)
• First player ever to hit two walk-off home runs in the same postseason (against the Angels (ALDS) and Yankees (ALCS), 2004)
• First player in Red Sox history to hit 40 or more home runs in three consecutive seasons (2004–2006)
• Set new record for home runs by a DH in 2005 (43), then again in 2006 (47)
• 6 seasons of at least 30 Home Runs and 100 RBI (2003–2007, 2010)
• Tied with Billy Hatcher for all-time post-season consecutive on-base streak (10)
• 85 extra-base hits or more for four consecutive years, something only 2 other players--Lou Gehrig (5) and Sammy Sosa (4)--have ever done.^[16]
• Ortiz's home run total increased each year from 2000–2006, starting with 10 home runs, and ending with 54.
• Became all time DH home run leader on September 15, 2009 by hitting his 270th as a Designated Hitter.
• Won 2010 Major League Baseball Home Run Derby in the final round against Hanley Ramirez.
• Has hit 10 career walk-off HR, the highest of any active player, and 20 walk-off hits total. He is currently 2 HR behind Babe Ruth and Mickey Mantle, the career leaders in walk-off HR.^[17]
• On April 2, 2011 Ortiz became MLB's all time RBI leader by a Designated Hitter.
• On July 27, 2011 Ortiz hit his 1,000th RBI with the Boston Red Sox.
• 2011 Roberto Clemente Award winner.

See also[link]

Wikimedia Commons has media related to: David Ortiz

Wikiquote has a collection of quotations related to: David Ortiz

	Biography portal
	Baseball portal
	Dominican Republic portal

• 50 home run club
• List of top 300 Major League Baseball home run hitters
• List of Major League Baseball RBI champions
• List of Major League Baseball home run champions

References[link]

External links[link]

• David Ortiz's MLB.com site
• David Ortiz On ESPN.com
• Career statistics and player information from MLB, or ESPN, or Baseball-Reference, or Fangraphs, or The Baseball Cube, or Baseball-Reference (Minors)
• Ten Questions for David Ortiz on Time.com (a division of Time Magazine)
• Stephan and Big Papi