Nutrition and Metabolism of Proteins 51The nutritional importance of nitrogenous com-
ponents in the diet was fi rst recognized in 1816 by
Magendie. He described experiments in dogs that
received only sugar and olive oil until they died within
a few weeks. It was concluded that a nitrogen source
was an essential component of the diet. Magendie’s
insightful views on nitrogen metabolism and nutri-
tion were followed by studies carried out by the
French scientifi c school, including Justus von Leibig,
who investigated the chemical basis of protein meta-
bolism and discovered that urea was an end-product
of protein breakdown in the body. Later, Leibig
founded a school of biochemical studies in Gissen
and later in Munich, Germany, from which Carl Voit
emerged as a distinguished scientist and laid the
foundations of modern studies of body nitrogen
balance. He, in turn, trained many famous scientifi c
celebrities, including Max Rubner, from Germany,
who studied the specifi c dynamic action of proteins
and their effects on energy metabolism, and Wilbur
Atwater and Graham Lusk, from the USA, who studied
food composition, protein requirements, and energy
metabolism. Through their work, and that of others,
theories of protein metabolism were proposed and
challenged, leading to the more or less contemporary
view which was established through the seminal work
of Rudolf Schoenheimer, conducted at Columbia
University, New York, in the mid-1930s and early
1940s. He applied the new tracer tool of stable isotope-
enriched compounds, especially amino acids, in the
study of dynamic aspects of protein turnover and
amino acid metabolism. Stable isotopes (such as^13 C,(^18) O, and (^15) N) are naturally present in our environ-
ment, including the foods we eat, and they are safe to
use in human metabolic studies. Using this approach,
Schoenheimer established the fundamental biological
principle of a continued tissue and organ protein loss
and renewal, which forms the basis for the dietary
need for protein or supply of amino acids and a utiliz-
able form of nitrogen.
4.3 Structure and chemistry of
amino acids
With the exception of proline, the amino acids
that make up peptides and proteins have the
same central structure (Figure 4.1; the A in this fi gure
and
Table 4.3 Biochemical roles of amino acids not directly related to
protein metabolism
Amino acid Biochemical function
Integration of carbon and nitrogen metabolism
Leucine, isoleucine, valine Ubiquitous nitrogen donors and
metabolic fuel
Ubiquitous nitrogen donor,
extracellular
Glutamate Transporter of four-carbon units
Glutamine See Table 4.2
Alanine Ubiquitous nitrogen donor,
extracellular
Transporter of three-carbon units
Aspartate Ubiquitous nitrogen donor
Transfer form of nitrogen from
cytoplasmic amino acids to
urea
Single carbon metabolism
Methionine Donor and acceptor of methyl
groups
Important role in single-carbon
metabolism
Glycine Donor of methylene groups
Serine Donor of hydroxymethylene
groups
Neurotransmitter synthesis
Histidine Precursor for histamine synthesis
Phenylalanine and tyrosine Precursors for tyramine,
dopamine, epinephrine, and
norepinephrine synthesis
Tryptophan Precursor for serotonin synthesis
Glutamate Precursor for γ-aminobutyric acid
synthesis
Miscellaneous
Arginine Immediate precursor for urea
Precursor for nitric oxide synthesis
Cysteine Potential intracellular thiol buffer
Precursor for glutathione and
taurine synthesis
Glycine Nitrogen donor for heme
synthesis
Histidine/β-alanine Precursors for carnosine synthesis
Medicine thesis in 1792. The fi rst amino acid to be
discovered was cystine, which was extracted from a
urinary calculus by Wallaston in England in 1810. It
was not until 1935 that threonine, the last of the so-
called nutritionally indispensable (essential) amino
acids for mammals, including man, was discovered
by WC Rose at the University of Illinois. Finally, the
term “protein” was invented by the Swedish chemist
Jons Jakob Berzelius (1779–1848) and this was later
accepted and promoted by the infl uential Dutch
chemist Gerhardus Mulder in 1838.