50 Introduction to Human Nutrition
according to a sequence directed by the base sequence
of the DNA (the genome), and so they serve as the
currency of protein nutrition and metabolism. The
Human Genome Project completed in 2000 revealed
that the human genome consists of only 30 000 genes,
whereas there may be hundreds of thousands of pro-
teins that are responsible for giving a human its par-
ticular characteristics and uniqueness. A new fi eld of
nutrition research has now opened up and is referred
to as “nutrigenomics,” which is the study of how
nutrition and genomics interact to infl uence health.
Proteins and amino acids fulfi ll numerous functions,
many of which are summarized in Table 4.1. Some
amino acids, such as glutamine (Tables 4.2 and 4.3),
play multiple roles. It is not surprising, therefore, that
inappropriate intakes of proteins and/or of specifi c
amino acids can have important consequences for
tissue and organ function, and the maintenance of
health and the well-being of the individual.
This chapter begins with a short historical perspec-
tive and then moves in Sections 4.3 and 4.4 to discuss
the structure, chemistry, and classifi cation of amino
acids. Section 4.5 is concerned with the biology of
protein and amino acid requirements, with Sections
4.6 and 4.7 describing how the requirements are
established and how they may be met, respectively.
Finally, Section 4.8 examines how factors other than
dietary protein can infl uence the requirements for
proteins and amino acids.
4.2 A historical perspective
The early history of protein metabolism and nutrition
is closely tied to the discovery of nitrogen and its
distribution in nature. The reason for this is that pro-
teins, on average, contain about 16% nitrogen by
weight (to convert nitrogen to protein it is necessary
to multiply by 6.25). Daniel Rutherford, in Edinburgh,
can be regarded as the discoverer of nitrogen, which
he called “phlogisticated air” in his Doctorate in
Table 4.1 Some functions of amino acid and proteins
Function Example
Amino acids
Substrates for protein
synthesis
Those for which there is a codon
Regulators of protein
turnover
Leucine; cysteine; arginine; glutamine
Regulators of enzyme
activity (allosteric)
Glutamate and NAG synthase
Phenylalanine and PAH activation
Precursor of signal
transducer
Arginine and nitric oxide
Methylation reactions Methionine
Neurotransmitter Tryptophan (serotonin); glutamine
Ion fl uxes Taurine; glutamate
Precursor of “physiologic”
molecules
Arg (creatinine); Glu-(NH 2 ) purines
Histidine/β-alanine (carnosine)
Cysteine/glycine/glutamate
(glutathione)
Transport of nitrogen Alanine; glu-(NH 2 )
Regulator of gene
transcription
Amino acid depletion and asparagine
synthase gene activation
Regulator of mRNA
translation
Leucine: alters activity of initiation
factor 4E-BP and P70 (6SK) via
mTOR signaling pathway
Proteins
Enzymatic catalysis Branched chain ketoacid
dehydrogenase
Transport B 12 binding proteins; ceruloplasmin;
apolipoproteins; albumin
Messengers/signals Insulin; growth hormone; IGF-1
Movement Kinesin; actin; myosin
Structure Collagens; elastin; actin
Storage/sequestration Ferritin; metallothionein
Immunity Antibodies; cytokine, chemokines
Growth; differentiation;
gene expression
Peptide growth factors; transcription
factors
IGF-1, insulin-like growth factor-1; NAG, N-acetyl glutamate; PAH,
phenylalanine hydroxylase; glu-(NH 2 ), glutamine.
Table 4.2 Multiple functions of an amino acid; glutamine as an
example
Substrate of protein synthesis (codons: CAA, CAG)
Anabolic/trophic substance for muscle; intestine (“competence
factor”)
Controls acid–base balance (renal ammoniagenesis)
Substrate for hepatic ureagenesis
Substrate for hepatic/renal gluconeogenesis
Fuel for intestinal enteroctyes
Fuel and nucleic acid precursor and important for generation of
cytotoxic products in immunocompetent cells
Ammonia scavenger
Substrate for citrulline and arginine synthesis
Nitrogen donor (nucleotides, amino sugars, coenzymes)
Nitrogen transport (1/3 circulating N) (muscle; lung)
Precursor of GABA (via glutamate)
Shuttle for glutamate (CNS)
Preferential substrate for GSH production?
Osmotic signaling mechanism in regulation of protein synthesis?
Stimulates glycogen synthesis
L-Arginine NO metabolism
Taste factor (umami)
CNS, central nervous system; GABA, γ-aminobutyric acid; GSH, growth-
stimulating hormone; NO, nitric oxide.