Organic Chemistry

Ulf Svante von Euler (1905–1983)

first identified prostaglandins—from

semen—in the early 1930s. He

named them for their source, the

prostate gland. By the time it was

realized that all cells except red

blood cells synthesize prostaglandins,

their name had become entrenched.

Von Euler was born in Stockholm and

received an M.D. from the Karolinska

Institute, where he remained as a

member of the faculty. He discovered

noradrenaline and identified its

function as a chemical intermediate

in nerve transmission. For this work,

he shared the 1970 Nobel Prize in

physiology or medicine with Julius

Axelrod and Sir Bernard Katz.

Section 26.5 Prostaglandins 011

26.5 Prostaglandins

Prostaglandinsare found in all body tissues and are responsible for regulating a vari-
ety of physiological responses, such as inflammation, blood pressure, blood clotting,
fever, pain, the induction of labor, and the sleep–wake cycle. All prostaglandins have
a five-membered ring with a seven-carbon carboxylic acid substituent and an eight-
carbon hydrocarbon substituent. The two substituents are trans to each other.

Prostaglandins are named in accordance with the format PGX, where X designates
the functional groups of the five-membered ring. PGAs, PGBs, and PGCs all contain a
carbonyl group and a double bond in the five-membered ring. The location of the dou-
ble bond determines whether a prostaglandin is a PGA, PGB, or PGC. PGDs and
PGEs are ketones, and PGFs are 1,3-diols. A subscript indicates the total
number of double bonds in the side chains, and and indicate the configuration
of the two OH groups in a PGF: indicates a cis diol and indicates a transdiol.

Prostaglandins are synthesized from arachidonic acid, a 20-carbon fatty acid with four
cis double bonds. In the cell, arachidonic acid is found esterified to the 2-position of
glycerol in many phospholipids. Arachidonic acid is synthesized from linoleic acid.
Because linoleic acid cannot be synthesized by mammals, it must be included in the diet.
An enzyme called prostaglandin endoperoxide synthase catalyzes the conversion of
arachidonic acid to the precursor of all prostaglandins. There are two forms of
this enzyme; one carries out the normal physiological production of prostaglandin,
and the other synthesizes additional prostaglandin in response to inflammation. The
enzyme has two activities: a cyclooxygenase activity and a hydroperoxidase activity. It
uses its cyclooxygenase activity to form the five-membered ring. In the first step of
this transformation, a hydrogen atom is removed from a carbon flanked by two double
bonds. This hydrogen is removed relatively easily because the resulting radical is

PGH 2 ,

HO

PGF 2

HO H

COOH

H

OH

PGE 1

O H O

COOH

HO H

OH

PGE 2

H

COOH

HO H

OH

O

R^1

R^2

H

R^1

H

R^1

H

H

O

R^1

R^2

O

R^2

HO

O

R^2

H

PGAs PGBs PGCs PGDs

“a” “b”

“a” “b”

b-hydroxy

prostaglandin skeleton

H COOH

H

For their work on prostaglandins,

Sune Bergström,Bengt Ingemar

Samuelsson, and John Robert Vane

shared the 1982 Nobel Prize in

physiology or medicine. Bergström

and Samuelsson were born in

Sweden—Bergström in 1916 and

Samuelsson in 1934. They are both at

the Karolinska Institute. Vane was

born in England in 1927 and is at the

Wellcome Foundation in Beckenham,

England.