Introduction to Human Nutrition

Nutrition and Metabolism of Proteins 55

as by the availability of appropriate quantities of
“nonessential” nitrogen. Further, the rate of synthesis
becomes of particular importance when considering
a group of amino acids, exemplifi ed by arginine,
cysteine, proline, and probably glycine. These amino
acids are frequently described as being conditionally
indispensable. That is, their indispensability is depen-
dent upon the physiological or pathophysiological
condition of the individual.
Finally, the phrase “normal growth” is critical in
two respects. First, it serves to emphasize that the defi -
nitions were originally constructed in the context of
growth. For example, for the growing rat arginine is
an indispensable amino acid, but the adult rat does
not require the presence of arginine in the diet and so
it becomes a dispensable amino acid at that later stage
of the life cycle. Of course, if the capacity to synthesize
arginine is compromised by removing a signifi cant
part of the intestine which produces citrulline, a
precursor of arginine, then the adult rat once again
requires arginine as part of an adequate diet. Second,
by confi ning the defi nition to growth, this fails to
consider the importance of amino acids to pathways
of disposal other than protein deposition. This aspect
of amino acid utilization will be considered below.

Chemical and metabolic characteristics as
bases of classifi cation

It is also possible to classify amino acids according to
their chemical and metabolic characteristics rather
than on the basis of their need for growth. Examination
of the amino acids that are generally considered to be
nutritionally indispensable for humans and most
other mammals indicates that each has a specifi c
structural feature, the synthesis of which cannot be
accomplished owing to the absence of the necessary
mammalian enzyme(s) (Table 4.4). Indeed, in obliga-

tory carnivores, such as cats, the further loss of some

critical enzyme(s) renders these animals particularly

dependent on dietary sources of specifi c amino acids,

such as arginine. The lack of arginine in a single meal

when given to a cat can be fatal. However, even within

this view, the important term is “de novo synthesis”

because some amino acids can be synthesized from

precursors that are structurally very similar. For

example, methionine can be synthesized both by

transamination of its keto acid analogue and by

remethylation of homocysteine. According to this

metabolic assessment of amino acids, threonine and

lysine are the only amino acids that cannot be formed

via transamination or via conversion from another

carbon precursor. In this narrower metabolic view,

they are truly indispensable amino acids. A contem-

porary nutritional classifi cation of amino acids in

human nutrition is given in Table 4.5.

Strictly speaking, a truly dispensable amino acid is

one that can be synthesized de novo from a nonamino

acid source of nitrogen (e.g., ammonium ion) and a

carbon source (e.g., glucose). Accordingly, and from

a knowledge of biochemical pathways, the only true

metabolically indispensable amino acid is glutamic

acid, and possibly also glycine. This is because they

can be synthesized from glucose and ammonium

ions, in the case of glutamate, and from carbon

dioxide and ammonium ions, in the case of glycine.

However, the in vivo conditions may differ in both

qualitative and quantitative terms from studies in

test-tubes or in isolated cells in culture; amino acid

metabolism in vivo is inherently more complex than

is immediately evident from a simple consideration

of biochemical pathways alone.

Table 4.4 Structural features that render amino acids indispensable
components of the diet of mammals

Amino acid Structural feature

Leucine, isoleucine, valine Branched aliphatic side-chain
Lysine Primary amine
Threonine Secondary alcohol
Methionine Secondary thiol
Tryptophan Indole ring
Phenylalanine Aromatic ring
Histidine Imidazole ring

Table 4.5 The dietary amino acids of nutritional signifi cance in

humans

Indispensable Conditionally indispensable Dispensable

Valine Glycine Glutamic acid (?)

Isoleucine Arginine Alanine

Leucine Glutamine Serine

Lysine Proline Aspartic acid

Methionine Cystine Asparagine

Phenylalanine Tyrosine

Threonine (Taurine)a

Tryptophan (Ornithine)a

Histidine (Citrulline)a

a Nonproteinogenic amino acids, which have nutritional value in

special cases.