Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

Abstract

Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others. Catabolism of arginine by arginase enzymes is the most common cause of an acquired arginine deficiency syndrome, frequently contributing to endothelial dysfunction and/or T-cell dysfunction, depending on the clinical scenario and disease state. Glutamine, an arginine precursor, is one of the most abundant amino acids in the body and, like arginine, becomes deficient in several conditions of stress, including critical illness, trauma, infection, cancer, and gastrointestinal disorders. At-risk populations are discussed together with therapeutic options that target these specific acquired amino acid deficiencies.

One Anastomosis Gastric Bypass Reconstitutes the Appropriate Profile of Serum Amino Acids in Patients with Morbid Obesity

“…Our study showed changes in glutamine metabolism and alterations in arginine and proline metabolism (p < 0.0001, impact 0.44; Table S4). Similar to glutamate, glutamine becomes an essential AA under oxidative stress, disease conditions, or catabolic states [15] and plays a role in intestinal mucosal integrity, antioxidative responses, and immunity and cell signaling [53]. Glutamine concentrations and the glutamine to glutamate ratio in plasma are strongly inversely associated with insulin resistance.…”

Sickle cell disease: a malady beyond a hemoglobin defect in cerebrovascular disease

“…Patients on L-glutamine showed significant reduction in the painful crises and hospitalization (NCT01179217). The rationale behind using L-glutamine is based on the fact that sickle RBCs have low nicotinamide adenine dinucleotide (NAD) and glutamine is a precursor of NAD, hence supplementation will counter the oxidant-dependent pathophysiology of sickle RBC [5,44–46]. Arginine is another anti-oxidant candidate, which has shown significant promise in the management of complications associated with SCD.…”

“…Arginine therapy resulted in promotion in the healing of long standing refractory ulcers and significant reduction in pain episodes in SCD patients [47,48]. Furthermore, Glutamine is an arginine prodrug which may also explain some of the benefits of these types of therapies [46]. …”

Dipeptiven® improves kidney pathology in a rat model of chronic kidney disease

“…Glutamine, the most abundant amino acid in the body, is considered conditionally essential in the catabolic state occurring among others in critical illness, trauma, and infection [1]. Administration of high doses of glutamine in critically ill patients, however, was associated with increased mortality in a large multi-center trial [2].…”