Amino acid ratios

Arginine homeostasis

Arginine (Arg) bioavailability has been assessed in terms of Global arginine bioavailability (GABR) calculated as Arg divided by the sum of ornithine (Orn) plus citrulline (Ctn). A related index is the arginine-to-ornithine ratio (AOr) that may reflect arginase activity. These indices have been related to mortality in SCD patients, but also to cardiovascular disease, diabetes, pulmonary hypertension (1), and recently, low levels have been reported in patients with COVID-19 (2).

Fischer’s ratio (FR)

FR is defined as sum of branched-chain amino acids (BCAAs: Leu, Ile and Val) divided by the sum of aromatic amino acids (AAA: Tyr, Phe). While BCAAs (and AAAs) tend to be elevated in patients with insulin resistance, prediabetes (and NAFLD), a different amino acid profile often develops in severe liver disease. FR normally is about 3.5 and can decline markedly (to 0.7-0.8) in patients with chronic liver damage, including fibrosis. A moderate decline in FR has been reported in Chronic congestive heart failure, Chronic obstructive pulmonary disease and Polycystic ovary syndrome (3).

GSG index

GSG index is the ratio of Glu divided by the sum of Ser and Gly. This index thus combines amino acids involved in glutathione synthesis. An index values higher than 0.36 (upper tertile) is associated with twofold higher prevalence of NAFLD. GSG index is associated with liver damage, the severity of liver fibrosis and shows a positive relation to liver enzymes, such as GGT and AST (3, 4).

Indication(s)

GABR and AOr should be measured together with asymmetric dimethylarginine (ADMA) (and homoarginine) for the assessment of endothelial function and cardiovascular risk. FR and GSG index may be useful for the assessment of the extent of liver damage in patients with NAFLD, NASH or liver fibrosis.

Specimen, collection and processing

Patient/subject: Prandial status affects concentration, which increases after arginine intake.
Matrix: EDTA plasma and serum. Arginine decreases (up to 70%) in samples with hemolysis.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: The blood sample must be centrifuged and the plasma/serum fraction put on ice, and frozen. Gln may be converted to Glu in serum/plasma stored at room temperature for hours.

Transportation

Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

Reported values: GABR: 0.2 – 1.2; AOr: 0.2 – 1.5; FR: 0.7 – 3.3; GSG: 0.2-0.6.

Literature

1. Morris, C. R., Hamilton-Reeves, J., Martindale, R. G., Sarav, M., & Ochoa Gautier, J. B. (2017). Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine. Nutr Clin Pract, 32(1_suppl), 30S-47S.
2. Rees, C. A., Rostad, C. A., Mantus, G., Anderson, E. J., Chahroudi, A., Jaggi, P. et al. (2021). Altered amino acid profile in patients with SARS-CoV-2 infection. Proc Natl Acad Sci U S A, 118, e2101708118.
3. Masoodi, M., Gastaldelli, A., Hyötyläinen, T., Arretxe, E., Alonso, C., Gaggini, M. et al. (2021). Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests. Nat Rev Gastroenterol Hepatol, 18(12), 835-856.
4. Leonetti, S., Herzog, R. I., Caprio, S., Santoro, N., & Tricò, D. (2020). Glutamate–serine–glycine index: A novel potential biomarker in pediatric non-alcoholic fatty liver disease. Children, 7(12), 270.

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