Glutamine

Asia Pacific J Clin Nutr 2004;13 (1):25-31 











 25

Review Article

Glutamine: metabolism and application in nutrition
support
Jane Coster Grad Dip Diet, Rosalie McCauley PhD and John Hall FRACS
Department of Surgery, The University of Western Australia, Perth, Australia


Glutamine is the most abundant free amino acid inthe body. It is avidly consumed by rapidly dividing cells,
such as those lining the gut, because its 5-carbon skeleton can provide energy whilst the nitrogen molecules
support the synthesis of nucleic acids. Patients who are maintained using conventional solutions of parenteral
nutrients become depleted in glutamine, which has led to the reclassification of glutamine as a conditionally
essentialnutrient. Unfortunately, glutamine is unstable in solution and produces toxic byproducts on
decomposition. This means that solutions of nutrients containing glutamine have a relatively short half-life,
which has led to the commercialisation of stable dipeptides containing glutamine. Although it is evident that
glutamine enhances nitrogen metabolism, there is a lack of consistent evidence fromthe initial clinical trials
demonstrating that supplementation with glutamine has specific clinical advantages. The next few years will
witness the performance of larger scale clinical trials and the results of these studies should define a more
certain role for glutamine in routine clinical practice.

Key Words: amino acids, glutamine, enteral nutrition, parenteral nutrition
Introduction
Glutamine, a 5-carbon amino acid with 2 amino groups, is
the most abundant free amino acid in the body.1 Specifically, glutamine accounts for more than 50% of the free
amino acid pool in skeletal muscle,2 25% of plasma free
amino acids3 and in the cerebrospinal fluid is present in a
10-fold greater concentration than any other amino acid.4
It was Sir Hans Krebs who, in 1935, firstdescribed
glutamine metabolism recognising that its commonality
between tissues and across species indicated a central
metabolic role.5,6 Glutamine functions as an intermediary
in energy metabolism, a substrate in the synthesis of peptide and non-peptide molecules including glutathione,
neurotransmitters and nucleotide bases. Glutamine also
has a homeostatic role as a regulator of systemic acidbasebalance and in the detoxification of ammonia. The
concept that the response to critical illness may be
modulated by glutamine-supplemented nutritional support
has gained a degree of acceptance in clinical practice.
This review offers a summary of glutamine metabolism
and a discussion of its application in nutrition therapy.

catabolic stress of trauma, but not sepsis, was associated
witha significant decrease in muscle glutamine concentration. Since then, using the same criteria, it has been
proposed that glutamine is conditionally essential for
preterm infants.10 The biochemical basis accounting for
glutamine becoming conditionally essential differs from
that of other conditionally essential amino acids. Glutamine may be synthesised from several essential amino
acids (Val,Leu, and Ile) whereas the de novo synthesis of
cysteine and tyrosine are dependent on the availability of
a single essential amino acid for their endogenous synthesis, methionine and phenylalanine respectively. Histidine is conditionally essential for a specified age group,
infants,11 whereas glutamine can become conditionally
essential for any age group. Cysteine is conditionally
essentialin low birth weight neonates secondary to an
immature synthetic pathway, specifically low cystathionase activity.12 Some are sceptical about the reclassification of glutamine and require unequivocal evidence of
a clinical response to supplementation as proof that endogenous synthesis can be inadequate.13

Glutamine is a conditionally essential amino acid
Glutamine was first proposed to be...