Introduction to Human Nutrition

Nutrition and Metabolism of Proteins 53

either their specifi c chemical properties or specifi c
metabolic interrelationships. Examples of the former
are the facility of methionine to donate a methyl group
in one-carbon metabolism, the propensity for the
amide group of glutamine to serve as a nitrogen source
for pyrimidine synthesis, or the sulfhydryl group of
cysteine forming disulfi de bonds for cross-linking.
The former metabolic relationship allows alanine
and glutamate (and glutamine) to provide a link
between carbohydrate and protein metabolism; the
latter enables the branched amino acids to function
when required, as a “universal” fuel throughout the
body.
Some of these amino acid and nitrogen compounds
are derivatives of other amino acids:

● creatine is formed from glycine, arginine, and
methionine and serves in intracellular energy
transduction

● dopamine is formed from tyrosine and fulfi lls a

neurotransmitter function

● ornithine can be formed from glutamate and serves

as both an intermediate in the urea cycle and a

precursor of the polyamines spermine and spermi-

dine, which are used in DNA packaging.

Finally, other amino acids (Figure 4.3) appear in pro-

teins via a post-translational modifi cation of a specifi c

amino acid residue in the polypeptide chain that is

being formed during protein synthesis.

In addition to serving the function as precursors

for protein synthesis, amino acids also serve as signal-

ing molecules modulating the process of protein

synthesis. The translation of mRNA into protein in

skeletal muscle is initiated from (1) the binding of

met-tRNA to the 40S ribosomal subunit to form the

43S preinitiation complex; (2) the subsequent binding

of this complex to mRNA and its localization to the

AUG start codon; and (3) the release of the initiation

factors from the 40S ribosomal complex to allow the

formation of the 80S ribosomal complex via the

joining of the 60S ribosomal subunit. Then the 80S

ribosomal complex proceeds to the elongation stage

of translation. The formation of the 43S preinitiation

complex is mediated by a heterotrimeric complex of

eIF–4F proteins. The signaling pathway regulating

mRNA translation involves the protein kinase termed

the mammalian target of rapamycin (mTOR). mTOR

regulates the formation of the eIF–4F complex via a

series of phosphorylation–dephosphorylation pro-

cesses of the downstream targets. The mTOR signal-

ing pathway is traditionally considered to be solely

involved in mediating the action of hormones. Recent

studies revealed that the branched-chain amino acids,

especially leucine, serve a unique role in regulating

mRNA translation via the same mTOR-signaling

pathway. Increased availability of leucine activates the

mTOR and its downstream targets. However, inhibi-

tion of the mTOR pathway by rapamycine partially

inhibits the stimulatory effect of leucine on protein

synthesis, indicating the involvement of an mTOR-

independent signaling pathway by leucine in the reg-

ulation of protein synthesis. The detailed mechanisms

involved in these regulations, especially those of the

mTOR-independent pathways, remain an active fi eld

of research.

Furthermore, individual amino acids play multiple

regulatory roles in health and diseased conditions.

N

Amino butyric acid

Figure 4.2 Physiologically important amino acid metabolites. Both
the metabolic relationship between alanine and glutamic acid and
their transamination partners, the keto acids pyruvate and α-
ketoglutarate, and the similarity between the catabolic oxidation
pathway of the branched-chain amino acids and the β-oxidation
pathway of saturated fatty acids are shown.