CLINICAL CASES
377
Phenylketones: Normally minor metabolites of phenylalanine that result
from the transamination of phenylalanine and further reduction. These
include phenylpyruvate and phenyllactate. These metabolites are ele-
vated when the conversion of phenylalanine to tyrosine is impaired.
PKU: Phenylketonuria; the pathologic condition of increased excretion of
phenylketones in the urine because of impaired conversion of pheny-
lalanine to tyrosine. Classical PKU is because of a genetic deficiency of
phenylalanine hydroxylase; however, other causes are deficiencies in
dihydropteridine reductase or in the biosynthesis of tetrahydrobiopterin.
D ISC U SSIO N
All 20 amino acids are needed for normal cellular growth and function. Amino
acids are the basic building blocks for all proteins synthesized in the cell. In
addition, the metabolism of amino acids provides carbon and nitrogen units that
are used in the synthesis of numerous important biomolecules including neuro-
transmitters, heme, purines, pyrimidines, polyamines, and various cellular-
signaling molecules. The carbon skeletons of amino acids can also be used as
an energy source. After removal of the amino group, amino acids can either be
directly oxidized or converted to glucose in the liver, providing carbon units to
other tissues for the production of adenosine triphosphate (ATP) through gly-
colysis and the tricarboxylic acid (TCA) cycle. Certain amino acids can be
directly interconverted to intermediates of the TCA cycle to provide a rapid
source of carbon units. Finally, catabolism of amino acids provides a means of
nitrogen and carbon removal from the body through their metabolism to urea
and CO2. Thus, all amino acids are necessary for life.
Apart from their biologic importance, amino acids are classified as essen-
tial or nonessential based on their ability to be synthesized in the body. The
term
essential
amino acid is used to identify those amino acids that must
be taken in through the diet (Table 41-1). There are 10 such amino acids for
which biosynthetic pathways do not exist in cells of the human body. In con-
trast, there are 11 amino acids that are termed
nonessential,
for which the
human body has biosynthetic pathways for their generation. One of these
amino acids, tyrosine, is synthesized from the essential amino acid pheny-
lalanine (Figure 38-2). In addition, it should be noted that arginine is listed as
both an essential and nonessential amino acid. Arginine is considered
nonessential because biosynthetic pathways for its generation do exist in cer-
tain cells of the body. Arginine can be synthesized from the amino acid gluta-
mate. Glutamate is first converted to ornithine, which is then converted to
arginine by enzymes of the urea cycle. The urea cycle is found only in the
liver, and thus the production of arginine through this pathway is limited. The
production of arginine through this pathway is likely sufficient for healthy
adults but may not be sufficient in times of growth when increased protein syn-
thesis augments the need for amino acids. Thus, in growing children and in
adults following surgery or trauma, arginine becomes an essential amino acid.
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