Introduction to Human Nutrition

Nutrition and Metabolism of Proteins 61

● In contrast, the rate of synthesis and degradation of
creatinine is relatively high and accounts for 10%
of the whole body fl ux of arginine and for 70% of
the daily intake of arginine.
● Similarly, the synthesis and turnover of glutathione
(a major intracellular thiol and important antioxi-
dant, formed from glutamate, glycine, and cyste-
ine) accounts for a high rate of cysteine utilization
such that it greatly exceeds the equivalent of the
usual daily intake of cysteine. Since continued glu-
tathione synthesis involves a reutilization of endog-
enous cysteine, a low intake of dietary methionine
and cyst(e)ine would be expected to have an unfa-
vorable infl uence on glutathione status and synthe-
sis. This has been shown experimentally to be the
case, especially in trauma patients and those suffer-
ing from acquired immunodefi ciency syndrome
(AIDS). Because glutathione is the most important
intracellular antioxidant that protects cells against
damage by reactive oxygen species, this would mean

that particular attention should be paid to such

amino acids in nutritional therapy in these groups

of patients.

Urea cycle enzymes and urea production

Finally, with reference to the major processes shown

in Figure 4.5, the urea cycle enzymes, which are dis-

tributed both within the mitochondrion and in the

cytosol (Figure 4.8), are of importance. The produc-

tion of urea may be viewed largely, but not entirely,

as a pathway involved in the removal of amino nitro-

gen and contributing to an adjustment of nitrogen

loss to nitrogen intake under various conditions. The

fi ve enzymes of urea biosynthesis associate as a tightly

connected metabolic pathway, called a metabalon, for

conversion of potentially toxic ammonia as well as

removal of excess amino acids via their oxidation

with transfer of the nitrogen to arginine and ulti-

mately urea. This is especially important when the

supply of protein or amino acids is high owing to

Mitochondrion

Carbamyl

phosphate

Citrulline

Citrulline

N-Acetyl glutamate

Arginine

Arginine

Urea

Ornithine

Argininosuccinate

Ornithine

Fumarate Aspartate

Acetyl CoA + Glutamate

Ornithine

Pi

+ HCO

• 
  
  
  
  • 2ATP
    Mg2+, K+
  
  
  
  

CPS

OTC

AS ASy

Arg

NH

+

43 + 2ADP + Pi

Figure 4.8 The urea cycle enzymes and their distribution in the liver. CPS, carbamoyl phosphate synthetase; OTC, ornithine transcarbamylase;
Asy, argininosuccinic synthetase; AS, argininosuccinate; Arg, arginase.