680 CHAPTER 17 Carbonyl Compounds I
DALMATIANS: DON’T TRY TO
FOOL MOTHER NATUREWhen amino acids are metabolized, the excess ni-
trogen is concentrated into uric acid, a compound with five
amide bonds. A series of enzyme-catalyzed reactions degrades
uric acid to ammonium ion. The extent to which uric acid is de-OC
H 2 N NH 2uric acid
excreted by:
birds, reptiles, insectsOOOHNN
HN
HH
Nallantoinmammalsallantoic acidmarine vertebratesureacartilaginous fish,
amphibiaOOOH 2 NN
HN
HH
NOOH 2 NN
HOenzyme enzymeenzymeCOH NH 2 enzyme+NH
4 X−N
Hammonium salt
marine invertebratesgraded in animals depends on the species. Birds, reptiles, and
insects excrete excess nitrogen as uric acid. Mammals excrete
excess nitrogen as allantoin. Excess nitrogen in aquatic animals
is excreted as allantoic acid, urea, or ammonium salts.Dalmatians, unlike other mammals, excrete high levels of
uric acid. The reason for this is that breeders of Dalmatians se-
lect dogs that have no white hairs in their black spots, and the
gene that causes the white hairs is linked to the gene that caus-
es uric acid to be converted to allantoin. Dalmatians, therefore,
are susceptible to gout (painful deposits of uric acid in joints).Sir Alexander Fleming (1881–1955)was
born in Scotland, the seventh of eight children
of a farmer. In 1902, he received a legacy from
an uncle that, together with a scholarship,
allowed him to study medicine at the
University of London. He subsequently became
a professor of bacteriology there in 1928. He
was knighted in 1944.Sir Howard W. Florey (1898–1968)was born
in Australia and received a medical degree
from the University of Adelaide. He went to
England as a Rhodes Scholar and studied at
both Oxford and Cambridge Universities. He
became a professor of pathology at the
University of Sheffield in 1931 and then at
Oxford in 1935. Knighted in 1944, he was
given a peerage in 1965 that made him Baron
Florey of Adelaide.Ernest B. Chain (1906–1979)was born in
Germany and received a Ph.D. from Friedrich-
Wilhelm University in Berlin. In 1933, he left
Germany for England because Hitler had
come to power. He studied at Cambridge, and
in 1935 Florey invited him to Oxford. In 1948,
he became the director of an institute in Rome,
but he returned to England in 1961 to become
a professor at the University of London.THE DISCOVERY OF PENICILLIN
Sir Alexander Fleming (1881–1955) was born in
Scotland. He was a professor of bacteriology at
University College, London. The story is told that one day
Fleming was about to throw away a culture of staphylococcal
bacteria that had been contaminated by a rare strain of the mold
Penicillium notatum.He noticed that the bacteria had disap-
peared wherever there was a particle of mold. This suggested to
him that the mold must have produced an antibacterial sub-
stance. Ten years later, Howard Florey and Ernest Chain
isolated the active substance—penicillin G (Section 17.16)—
but the delay allowed the sulfa drugs to be the first antibiotics.
After penicillin G was found to cure bacterial infections in
mice, it was used successfully in 1941 on nine cases of human
bacterial infections. By 1943, penicillin G was being produced
for the military and was first used for war casualties in Sicily
and Tunisia. The drug became available to the civilian popula-
tion in 1944. The pressure of the war made the determination of
penicillin G’s structure a priority because once its structure was
determined, large quantities of the drug could be produced.
Fleming, Florey, and Chain shared the 1945 Nobel Prize in
physiology or medicine. Chain also discovered penicillinase,
the enzyme that destroys penicillin (Section 17.16). Although
Fleming is generally given credit for the discovery of peni-
cillin, there is clear evidence that the germicidal activity of the
mold was recognized in the nineteenth century by Lord
Joseph Lister (1827–1912), the English physician renowned
for the introduction of aseptic surgery.