chapter 17
Protein and Amino Acid Metabolism
C ystein e
In the biosynthesis of cysteine, the sulfur comes from
methionine by transsulfuration, and the carbon skeleton
and the amino group are provided by serine (Figure 17-16).
Cysteine regulates its own formation by functioning
as an allosteric inhibitor of cystathionine
a -
Ketobutyrate is metabolized to succinyl-CoA by way of
propionyl-CoA and methylmalonyl-CoA.
Cysteine is required for the biosynthesis of glu-
tathione and of CoA-SH. A synthetic derivative, N-
acetylcysteine, is used to replenish hepatic levels of glu-
tathione and prevent hepatotoxicity due to overdosage
with acetaminophen. When high concentrations of ace-
toaminophen are present in the liver, the drug undergoes
N-hydroxylation to form N-acetyl-benzoquinoneimine,
which is highly reactive with sulfhydryl groups of pro-
teins and glutathione and causes hepatic necrosis. N-
Acetylcysteine is used as a mucolytic agent (e.g., in cystic
fibrosis) because it cleaves disulfide linkages of mucopro-
teins. Cysteine and cystine are interconverted by NAD-
dependent cystine reductase and nonenzymatically by an
appropriate redox agent (e.g., GSH).
The major end products of cysteine catabolism in hu-
mans are inorganic sulfate, taurine, and pyruvate. Taurine
is a /1-amino acid that has a sulfonic acid instead of a
L-M ethionine
M ethionine ad en o sy ltran sferase
PP, + P,
S-A denosylm ethionine
- (— CH,) in m ethyltransferase reaction
S-A denosylhom ocysteine
A denosylhom ocysteinase
" — A denosine
HS— C H — CH— CH— C O C f
L -H om ocysteine
O O C — CH— CH,— s -
C ystathionine p -sy n th a se (pyridoxal phosphate)
-CH — CH,— CH— C O O "
i -C ystathionine
^ -h,o
"O O C — C H — C H — SH
l -C y stein e
C ystathionine T -lyase (pyridoxal phosphate)
CH,— CHj— C — C O O
---------- Sucdnyl-C oA
a-K eto b u ty rate
FIGURE 17-16
Biosynthesis of cysteine. The sulfur is derived from methionine, and the
carbon skeleton and amino group are derived from serine.
carboxylic acid group. Taurine is conjugated with bile
acids in the liver (Chapter 19) and is readily excreted by the
kidney. It is a major free amino acid of the central nervous
system (where it may be an excitatory neurotransmitter)
and the most abundant in the retina; it also occurs in other
tissues (e.g., muscle, lung).
Sulfate can be converted to the sulfate donor compound
3'-phosphoadenosine-5'-phosphosulfate (PAPS) in a two-
step reaction (Figure 17-17). PAPS participates in the
sulfate esterification of alcoholic and phenolic functional
groups (e.g., in synthesis of sulfolipids and glycosamino-
A b n o rm a lities In vo lvin g S u lfu r-C o n ta in in g
A m in o A cid s
Deficiencies of methionine adenosyltransferase, cys-
tathionine /1-synthase, and cystathionine y-lyase have
been described. The first leads to
h yperm eth io n in em ia
but no other clinical abnormality. The second leads to
h y-
p erm eth io n in em ia , h yp erh o m o cystein em ia ,
hom o-
cystin u ria .
The disorder is transmitted as an autosomal
recessive trait. Its clinical manifestations may include
skeletal abnormalities, mental retardation, ectopia lentis
(lens dislocation), malar flush, and susceptibility to arte-
rial and venous thromboembolism. Some patients show
reduction in plasma methionine and homocysteine con-
centrations and in urinary homocysteine excretion after
large doses of pyridoxine. Homocystinuria can also result
from a deficiency of
co b a la m in
(vitamin B
1 2
) or folate
metabolism. The third, an autosomal recessive trait, leads
to cystathioninuria and no other characteristic clinical
Hereditary sulfite oxidase deficiency can occur alone
or with xanthine oxidase deficiency. Both enzymes con-
tain molybdenum (Chapter 27). Patients with sulfite ox-
idase deficiency exhibit mental retardation, major motor
seizures, cerebral atrophy, and lens dislocation. Dietary
deficiency of molybdenum (Chapter 37) can cause defi-
cient activity of sulfite and xanthine oxidases.
C ystin u ria
is a disorder of renal and gastrointestinal
tract amino acid transport that also affects lysine, or-
nithine, and arginine. The four amino acids share a com-
mon transport mechanism (discussed above). Clinically, it
presents as urinary stone disease because of the insolubil-
ity of cystine. In cystinosis, cystine crystals are deposited
in tissues because of a transport defect in ATP-dependent
cystine efflux from lysosomes (discussed above).
H o m o cystein e
H o m o cystein e
is an amino acid not found in pro-
teins. Its metabolism involves two pathways; one is
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