Clinical Amino Acids: N-Acetylcysteine, Glutamine and Creatine

Mechanism

Specific cellular action mechanisms

1. N-Acetylcysteine (NAC) and the Glutathione Pool

NAC is an acetylated derivative of the amino acid L-cysteine that acts selectively in the biosynthesis of glutathione (GSH), the main endogenous cellular antioxidant. Cysteine ​​is the limiting amino acid in the synthesis of GSH by the enzyme γ-glutamylcysteine ​​synthetase. In the lung and liver parenchyma, NAC provides free sulfhydryl groups that directly reduce the disulfide bridges of the acidic mucoproteins of the mucus, reducing its physical viscosity (mucolytic effect).

2. L-Glutamine and Enterocyte Trophism

Glutamine is the most abundant free amino acid in plasma. It acts as the preferred energy substrate for rapidly changing cells, such as enterocytes of the intestinal mucosa and active lymphocytes. During periods of severe catabolic stress (severe burns, sepsis), tissue consumption exceeds endogenous muscle synthesis of glutamine, converting it to a conditionally essential amino acid. Its supplementation maintains the integrity of the tight junctions of the epithelium, preventing bacterial translocation from the intestinal lumen to the blood.

3. Creatine Monohydrate and Energy Hydrolysis

Exogenous creatine is actively taken up by skeletal muscle fibers and phosphorylated by the enzyme creatine kinase to become phosphocreatine (PCr). Phosphocreatine acts as a mobile reserve of high-energy phosphates, capable of instantly regenerating ATP molecules from ADP during high-intensity, short-duration contractions:

Indicators and dose

Clinical Indications and Dosage of NAC

• Acute Paracetamol Intoxication: Standard 21-hour NAC intravenous infusion protocol: initial loading bolus of 150 mg/kg diluted in 5% dextrose to be passed over 60 minutes, followed by a continuous infusion of 50 mg/kg over 4 hours and finally 100 mg/kg over an additional 16 hours.
• Adjuvant Mucolytic Treatment: 600 mg daily orally in the form of effervescent tablets.

Security

NAC as a Clinical Antidote in Paracetamol Poisoning

Paracetamol overdose poisoning saturates the physiological hepatic glucuronidation and sulfoconjugation pathways, diverting drug metabolism toward the oxidative CYP2E1 pathway. This pathway generates the highly reactive metabolite NAPQI (N-acetyl-p-benzoquinoneimine), which is extremely cytotoxic and binds covalently to hepatocyte proteins, inducing fulminant acute liver necrosis.

Under normal conditions, NAPQI is quickly neutralized by conjugating with hepatic glutathione. However, in the event of an overdose of paracetamol, glutathione reserves are depleted within a few hours. Intravenous or enteral administration of N-acetylcysteine acts effectively by providing cysteine for the synthesis of new glutathione and directly interacting chemically with residual NAPQI, preventing liver necrosis if administered within the first 8 to 10 hours of ingestion.