Provided herein are methods of treating a subject with hyperammonemia or aurea cycle disorder. The methods compriseadministering to a subject in need thereof a therapeutic amount of a glucagonsignaling pathway inhibitor, such that ammonia levelsare lowered or that amino acid metabolism enzymes are down-regulated, or acondition or disease characterized by hyperammonemiais mediated, or at least one symptom or complication associated with thecondition or disease is alleviated or reduced in severity. Theglucagon signaling pathway inhibitor can be a small molecule inhibitor of thesignaling pathway, an antisense inhibitor of the signalingpathway, shRNA, siRNA, a GCG neutralizing monoclonal antibody, a GCGRantagonist, a peptide inhibitor of the signaling pathway,a DARPin, a Spiegelmer, an aptamer, engineered Fn type-III domains, etc. Thetherapeutic methods are useful for treating a humansuffering from hyperammonemia or a urea cycle disorder.
