Human Physiology, 14th edition (2016)

96 Chapter 4

pathway, the intermediates and final products of the alternate
pathway will increase ( fig. 4.10 ). An abnormal increase in the
production of these products can be the cause of some meta-
bolic diseases.
One of the conversion products of phenylalanine is a
molecule called DOPA, an acronym for dihydroxyphenylala-
nine. DOPA is a precursor of the pigment molecule melanin,
which gives skin, eyes, and hair their normal coloration. The
condition of albinism results from an inherited defect in the
enzyme that catalyzes the formation of melanin from DOPA
( fig. 4.11 ). Besides albinism and PKU (described in the next
Clincial Applications box), there are many other inborn
errors of amino acid metabolism, as well as errors in carbo-
hydrate and lipid metabolism. Some of these are described
in table 4.4.

Figure 4.11 Metabolic
pathways for the degradation of the
amino acid phenylalanine. Defective
enzyme 1 produces phenylketonuria
(PKU), defective enzyme 5 produces
alcaptonuria (not a clinically significant
condition), and defective enzyme 6
produces albinism.

Phenylalanine

Enz

1

Enz

2

Enz

3

Enz

4

Phenylpyruvic acid

Tyrosine

Homogentisic acid

Dihydroxyphenylalanine

(DOPA) Enz 6

Melanin

Metabolized to CO 2 + H 2 O

Enz 5

Figure 4.9 End-product inhibition in
a branched metabolic pathway. Inhibition is
shown by the red arrow in step 2.

Enz 2

BC

Enz4'

D' E'

Enz 4

DE

Enz^3

Enz

3'

Enz 1

A

Enz5'

F'

Enz 5

F This pathway

becomes

favored

if this final

product

accumulates.

2

3

1

Inhibition

Figure 4.10 The effects of an
inborn error of metabolism on a branched
metabolic pathway. The defective gene
produces a defective enzyme, indicated here
by a line through its symbol.

Enz 2

BC

Enz4'

D' E'

Enz 4

DE

Enz

3

Enz

(^3) '
Enz 1
A
Enz5'
F'
Enz 5
F This pathway
cannot be
followed. Lack
of “F” may
cause disease.
Production of
these molecules
increases and
may cause
disease.
Abnormal gene
makes defective
enzyme (Enz 3 ).
2
3
1
CLINICAL APPLICATION
Phenylalanine—an essential amino acid (because our bodies
cannot produce it, but require it for the production of proteins)—
is normally converted by the enzyme phenylalanine hydroxylase
(designated Enz 1 in figure 4.11 ) into the amino acid tyrosine. In
phenylketonuria (PKU), a disease inherited as an autosomal
recessive trait, this enzyme is defective. Phenylalanine accumu-
lates and is converted instead into phenylpyruvic acid and other
products. Untreated PKU can result in severe mental retardation
and other neurological problems, but fortunately this condition is
tested for in all neonates (newborns) by analyzing a small blood
sample drawn from a heel prick. The damaging consequences
of PKU can be avoided by a lifelong diet low in phenylalanine
and supplemented with the needed amounts of phenylalanine
and tyrosine.