360
chapter 17
Protein and Amino Acid Metabolism
acids into cells. Variations in the clinical manifestations of
PKU may reflect differences in this disturbance. Defects
in pigmentation of skin and hair (light skin and hair)
may be caused by interference of melanin formation by
phenylalanine and its metabolites and also by lack of
tyrosine.
Melanin
Melanin
is an insoluble, high-molecular-weight poly-
mer of 5,6-dihydroxyindole, which is synthesized from
tyrosine (Figure 17-23). It is produced by pigment cells
(melanocytes) in cytoplasmic organelles (melanosomes).
In
the
epidermis,
melanocytes
are
associated
with
kératinocytes, which contain melanosomes supplied by
melanocytes via dendritic processes. Color variation in
human skin reflects the amount of melanin synthesized
in melanosomes. Melanin synthesis is apparently under
hormonal and neural regulation.
The first two steps in the synthesis of melanin are
catalyzed by tyrosinase, a copper-containing oxidase,
which converts tyrosine to dopaquinone.
All subse-
quent reactions presumably occur through nonenzymatic
auto-oxidation, in the presence of zinc, with forma-
tion of the black to brown pigment eumelanin. The
yellow to reddish brown, high-molecular-weight poly-
mer known as pheomelanin and the low-molecular-weight
trichromes result from addition of cysteine to dopaquinone
and
further
modification
of the
products.
Pheome-
lanins and trichromes are primarily present in hair and
feathers.
Abnormalities o f Tyrosine Metabolism
Hepatic cytosolic tyrosine aminotransferase (tyrosine
transaminase) deficiency produces
tyrosinemia type II,
an autosomal recessive trait marked by hypertyrosine-
mia and tyrosinuria. Clinical manifestations may include
corneal erosions and plaques, inflammation (from intracel-
lular crystallization of tyrosine), and mental retardation.
Low-tyrosine and low-phenylalanine diets are beneficial.
Tyrosinosis
is presumably due to fumarylacetoacetate
hydrolase deficiency and has a high prevalence in the
French-Canadian population of Québec. It is associ-
ated with abnormal liver function, renal tubular dys-
function, anemia, and vitamin D-resistant rickets. Tran-
sient
tyrosinemia
of the newborn, particularly in prema-
ture infants, is the most common form of tyrosinemia in
infancy.
Alcaptonuria
is a rare metabolic hereditary disease in
which homogentisic acid is eliminated in urine, which
darkens upon exposure to air owing to oxidation of
Tyrosine
3,4-Dihydroxyphenylalanine
(dopa)
[O]-^
H.0*^
Tyrosinase
H
Dopachrom e
Dopa quinone
COr^
Zn
5,6-Dihydroxy indole
Cysteine
lndole-5,6-quinone
Trichrom es*
/
/
Pheom elanins
Polym erization
H
F I G U R E 1 7 -2 3
Biosynthesis of melanins.
homogentisic acid. The biochemical lesion is homogen-
tisic acid oxidase deficiency. Clinical features include
pigmentation of cartilage and other connective tissues
(ochronosis) later in life from deposition of oxidized ho-
mogentisic acid. Patients nearly always develop arthritis
in later years, but the relationship between pigment depo-
sition and arthritis is not understood.
Lack of melanin production (
hypomelanosis
) gives rise
to several hereditary disorders collectively known as
al-
binism.
Some forms result from deficiency of tyrosinase.
The inheritance pattern of albinism varies with type. Af-
fected individuals have increased susceptibility to various
