Is α-ketoisocaproyl-glutamine a suitable glutamine precursor to sustain fibroblast growth?

Background: Glutamine is considered an essential nutrient for cellular growth. Aim: To test the suitability of α-ketoisocaproyl-Gln (Kic-Gin) as a new glutamine (Gin) precursor to sustain human fibroblast growth. Methods: [3H] thymidine uptake into cellular DNA of human fibroblasts. Extracellular and intracellular aminoacid patterns were determined with peptides and acylated compounds. Results: L-alanyl-L-glutamine (used here as a recognized Gin precursor) promoted DNA synthesis, whileN-acetyl-L-glutamine (used here as a negative control since it is known to be a poor Gin precursor) and α-ketoisocaproyl-glutamine had no effect. Alanyl-glutamine progressively gave rise to free glutamine in the growth medium. In contrast, glutaminesupplied in acylated form was poorly available and did not appear in free form in the medium. In addition, only alanyl-glutamine increased intracellular glutamine and glutamate levels. In contrast,Kic-Gln was able to sustain net protein synthesis as judged by total protein content and reduced intracellular levels of most essential amino acids. Conclusion: Kic-Gln appears to be a poor extra-cellular precursor of Gin to sustain cell growth.