62 Introduction to Human Nutrition
variations in the exogenous intake or when there is a
high rate of whole body protein breakdown in cata-
bolic states, as occurs in severe trauma and following
overwhelming infection.
Altered intakes of indispensable amino acids and
of total nitrogen result in changes in rates of amino
acid oxidation and the output of urea nitrogen in
urine. There is a roughly parallel change in urea pro-
duction and excretion throughout a relatively wide
range of change in the level of dietary nitrogen intake
above and below physiological requirement levels.
Part of this urea enters the intestinal lumen, where
there is some salvaging of urea nitrogen, via intestinal
hydrolysis of urea to form ammonia. This ammo-
nium nitrogen can be made available to the host for
the net synthesis of dispensable or conditionally
indispensable amino acids. However, the quantitative
extent to which this pathway of nitrogen fl ow serves
to maintain whole body N homeostasis and retention
under normal conditions is a matter of uncertainty.
The ammonia from urea could also enter the nitrogen
moiety of the indispensable amino acids, but this
would be essentially by an exchange mechanism and
so would not contribute to a net gain of these amino
acids in the body.
The reutilization of urea nitrogen starts from the
hydrolysis of the intact urea molecule. By constantly
infusing the [^15 N 2 ]-urea tracer, the appearance of the
singly labeled [^15 N]-urea should represent the extent
of urea hydrolysis. A 24 hour constant infusion of
[^15 N 2 ]-urea revealed a minimal amount of [^15 N]-urea
appearance in the plasma, and a linear relationship
over a wide range of protein intake versus total urea
production and urea hydrolysis. Furthermore, the
possible metabolic pathways involved in the assimila-
tion of ammonia generated from urea nitrogen
include (1) citrulline synthesis, (2) l-glutamate dehy-
drogenase pathway in the mitochondria, and (3)
glycine synthase. The net formation of amino nitro-
gen from these pathways is quantitatively minimal
compared with the metabolic fl uxes of these amino
acids through their major pathways, such as protein
turnover, dietary intake, and de novo synthesis (of the
nutritionally dispensable amino acids only).Summary of the metabolic basis for
protein and amino acid requirements
It should be evident from this account of the underly-
ing aspects of the needs for α-amino nitrogen and
indispensable amino acids, that the “metabolic”
requirement can usefully be divided: fi rst, into those
needs directly associated with protein deposition, a
critical issue in infants, early childhood nutrition, and
during recovery from prior depletion due to disease
or malnutrition; and, second, into those needs associ-
ated with the maintenance of body protein balance,
which accounts for almost all of the amino acid
requirement in the healthy adult, except for that due
to the turnover and loss of the various physiologi-
cally important nitrogen-containing products, some
of which were mentioned above. Quantifying the
minimum needs for nitrogen and for indispensable
amino acids to support growth should be relatively
easy, in principle, because these needs are simply the
product of the rate of protein nitrogen deposition and
the amino acid composition of the proteins that are
deposited. Here, it may be pointed out that the gross
amino acid composition of whole body proteins
shows essentially no difference among a variety of
mammals, including humans (Table 4.6). Thus, at theTable 4.6 Essential amino acid composition of mixed body protein of immature mammals
Amino acid composition (mg/g protein)
Lysine Phenylalanine Methionine Histidine Valine Isoleucine Leucine ThreonineRat 77 43 20 30 52 39 85 43
Human 72 41 20 26 47 35 75 41
Pig 75 42 20 28 52 38 72 37
Sheep 75 42 17 23 53 33 79 47
Calf 69 39 18 27 42 30 74 43
From Reeds PJ. Dispensable and indispensable amino acids for humans. J Nutr 2000; 130 : 1835S–1840S. Reprinted with permission of The
American Society for Nutrition.