CASE FILES: BIOCHEMISTRY
When liver function is severely impaired or when collateral links between
the portal and venous blood vessels arise as occurs in cirrhosis, the ability of
the liver to detoxify ammonia to urea is compromised resulting in hyper-
ammonemia. This can be exacerbated by an increase in the ammonia load,
such as can occur from gastrointestinal bleeding. When blood ammonia lev-
els rise, ammonia builds up inside the cells and drives the GDH reaction to
form Glu, thus depleting a-KG stores and slowing the tricarboxylic acid
(TCA) cycle. This is particularly devastating to the brain, which must have an
active TCA cycle to produce the energy needed for brain function.
C O M P R E H E N SIO N Q U E ST IO N S
-month-old infant was admitted to the hospital in a coma and a
temperature of 39.4°C (102.9°F). His pulse was elevated, his liver was
enlarged, and an electroencephalogram was grossly abnormal. Since
the infant could not retain milk given by gavage feeding, intravenous
glucose was administered. He improved rapidly and came out of the
coma in 24 hours. Analysis of his urine showed abnormally high
amounts of glutamine and uracil, which suggested a high blood ammo-
nium ion concentration. The laboratory confirmed this.
Considering the data, which enzyme may be defective in this patient?
B. Carbamoyl phosphate synthetase I
C. Glutamate dehydrogenase
E. Ornithine transcarbamoylase
[37.2] A newborn male infant was diagnosed as having phenylketonuria
(PKU), and immediately placed on diet low in phenylalanine (Phe);
careful compliance with the diet and frequent monitoring of the
patient’s plasma Phe level resulted in the level being maintained at the
lower limit of the normal range. The patient appeared to be developing
normally until 4 months of age, when he developed truncal hypotonia
and spasticity of the limbs. Despite being on a low-phenylalanine diet,
at 5 months the patient had several grand mal (epileptic) seizures. After
an abnormal Phe-loading test, the patient’s urine was found to have a
markedly elevated urinary biopterin concentration.
Which of the following enzymes is most likely deficient in this patient?
A. Dihydropteridine reductase
B. GTP cyclohydrolase I
C. Phenylalanine hydroxylase
D. Tryptophan hydroxylase
E. Tyrosine hydroxylase