358
chapter 17
Protein and Amino Acid Metabolism
/
\
NH ?
I
C H — C H — C 0 0 ~
0
2
P h e n y lalan in e
V h y d ro x y lase
T e trah y d ro -
Q uinonoid-
P h e n y la la n in e
biopterin
dihydrobiopterin
I N A D (P)
NA D (P)H+H +| '
tt.U
r .
-----\
* v
ho^O
it linnnftirï-
D ihydrofolate
re d u c ta s e
D ihydropteridine
re d u c ta s e
5
^•N A D P
^ NADPH + H+
' — 7 ,
8
-Di hydro b io p terin
HO
r
\
n h ;
I
CH.— C H — C O O “
T y ro sin e
-K eto g lu tarate
T y ro sin e tra n s a m in a s e
^ G l u t a m a t e
O
II
-CH—C— c o o
•
*
p -H y d ro x y p h en y lp y ru v ate
H ydroxylation, shift
of th e sid e ch ain ,
d ecarb o x y latio n
ic
acid o x id a se ; a sco rb ic
.acid; C uJ+
^—CO,
p-H ydroxyphenylpyruv
c o o
1
C H
2
1
CH
1
c = o
II
1
HC
1
C H
2
1
coo"
coo"
F u m a ra te
A c e to a c e ta te
h 2o
| F u m a ry la c e to a c e ta s e
C H 2C O O
H o m o g en tisic acid
H o m o g en tisic acid
o x id a se ; a sc o rb ic
acid ; G S H
“OOC^ ^H
V
C
C H
2
C H ,
/ y y w
o
o
F u m a ry la c e to a c e ta te
COO'
HJ
M a le y la c e to a c e ta te
HC
CH?
C H
2
is o m e ra s e
\ /
\ /
\
■
c
c
COO
o
o
M ale y la c eto a c e tate
FIGURE 17-20
Conversion of phenylalanine to tyrosine and the oxidative pathway of tyrosine.
6-pyruvoyl tetrahydrobiopterin synthase leads to
hyper-
phenylalaninemia.
Phenylketonuria (PKU)
Deficiency
of phenylalanine
hydroxylase,
tetrahy-
drobiopterin, or dihydropteridine reductase results in
phenylketonuria (PKU), an autosomal recessive trait. Be-
cause phenylalanine accumulates in tissues and plasma
(hyperphenylalaninemia), it is metabolized by alternative
pathways and abnormal amounts of phenylpyruvate ap-
pear in urine (Figure 17-22). Phenylalanine hydroxylase
deficiency may be complete (classic PKU, type I) or partial
(types II and III). Many mutations of the phenylalanine hy-
droxylase gene have been identified (missense, nonsense,
insertions, deletions, and duplications) leading to PKU or
non-PKU hyperphenylalaninemia.
The incidence of classic PKU is about 1 in 10,000-
20,000 live births and exhibits considerable geographic
variation (the incidence in Ireland is 1 in 4000, whereas
the condition is rare among blacks and Asians). About
2% of hyperphenylalaninémie infants have a deficiency
of biopterin or biopterin reductase. The most important
clinical presentation is mental impairment. Diagnosis can
be made early in the neonatal period by measurement
of phenylalanine concentration in blood collected from
