Introduction

Glutamine is the most abundant free amino acid in the human body. Although glutamine has been traditionally classified as a nonessential amino acid, decreased levels have been noted during periods of metabolic stress leading to its reclassification as a conditionally essential amino acid. Glutamine is a five-carbon amino acid with two amino moieties (Figure 5.1), and it accounts for 35 to 50% of all amino acid nitrogen transported in blood. It is produced primarily in the muscles from glutamate (Figure 5.2) and plays a key role in the transport of nitrogen between organs. Over the past several decades, research has revealed a plethora of important functions of glutamine in the human body (Table 5.1). It is a primary fuel for rapidly dividing cells, such as enterocytes, hepatocytes, and immune cells, as well as a nitrogen carrier. In addition to protecting the body against the toxic effects of ammonia, glutamine is the precursor to several important metabolic agents, including glutathione, arginine, taurine, and the building blocks of DNA and RNA.

Many studies have documented that glutamine levels are decreased when the body is physically and metabolically stressed, such as in patients with sepsis or traumatic injury. Researchers have actively sought the clinical significance of this decrease. It has been proven that glutamine is important for maintaining the barrier function of the intestines, promoting pancreatic growth, preventing hepatic steatosis, reducing ischemic reperfusion injury, and maintaining immune cell function. Based on this research, many have tried to elucidate whether glutamine supplementation in the catabolic state is beneficial to patients. Clinical trials have shown that supplementation with glutamine decreases infectious complications and length of hospital stay and in some patient populations reduces morbidity and mortality. However, there is currently much debate as to the optimal method of glutamine delivery and the amount needed to affect outcomes. A thorough background of glutamine metabolism in the normal metabolic state of the body is important before discussing the implications of glutamine deficiency and supplementatin.

TABLE 5.1

Important Functions of Glutamine

Gastrointestinal system Energy source for enterocytes maintains mucosal integrity and barrier

Immune system

Nervous system Hepatobiliary system

Renal system function of the gut Provides building blocks of DNA and RNA for rapidly dividing cells; energy source for macrophages, lymphocytes, and neutrophils; precursor to glutathione, a powerful antioxidant Acts as a neurotransmitter

Transports ammonia from peripheral tissue to liver for conversion into urea; important for pancreatic growth and function Metabolized in the kidney to regulate acid-base homeostasis; substrate for gluconeogenesis in kidney

FIGURE 5.1 Molecular structure of glutamine.

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