I. As a Metabolic Hub of Sulfur-Containing Amino Acids
L-alanyl-L-cystine, a dipeptide linked by alanine and cystine through peptide bonds, can be rapidly hydrolyzed by peptidases into alanine and cystine in vivo, thereby participating in key metabolic pathways:
Decomposition and Utilization of Cystine
Cystine hydrolysis generates two molecules of cysteine, an essential precursor for glutathione (GSH) synthesis. As a vital intracellular antioxidant, GSH scavenges free radicals (e.g., H₂O₂) and protects cells from oxidative damage, particularly in the liver, red blood cells, and immune cells. For example, reduced GSH content in hepatocytes impairs detoxification, while supplementation with L-alanyl-L-cystine enhances GSH synthesis efficiency, boosting liver tolerance to drugs and toxins.
Gluconeogenesis of Alanine
Alanine is transported via blood to the liver, where it undergoes transamination to form pyruvate, participating in gluconeogenesis to supply energy. This process is crucial during starvation or high-intensity exercise, maintaining blood glucose stability and preventing excessive muscle protein breakdown.
II. Antioxidant and Oxidative Stress Regulation
The antioxidant function of L-alanyl-L-cystine is realized through the following pathways:
Direct Free Radical Scavenging
Although the sulfhydryl group (-SH) in cystine exists as a disulfide bond (-S-S-), hydrolyzed cysteine directly binds to hydroxyl radicals (・OH), peroxyl radicals (ROO・), etc., blocking oxidative chain reactions. Studies show that in myocardial ischemia-reperfusion models, L-alanyl-L-cystine supplementation reduces intracellular reactive oxygen species (ROS) accumulation and lipid peroxidation products (e.g., malondialdehyde), alleviating myocardial damage.
Regulation of Antioxidant Enzyme Systems
As a sulfur source, cysteine promotes the synthesis of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx). For instance, in a pulmonary fibrosis animal model, L-alanyl-L-cystine inhibits oxidative damage to alveolar epithelial cells by enhancing GPx activity, delaying fibrotic progression.
III. Participation in Detoxification and Liver Protection
Heavy Metal Chelation
The sulfhydryl group of cysteine has high affinity for heavy metals like mercury, cadmium, and lead, forming stable sulfhydryl-metal complexes excreted via urine. Clinical studies indicate that L-alanyl-L-cystine adjuvant therapy for heavy metal poisoning improves metal excretion efficiency and reduces renal and neurotoxicity.
Activation of Hepatic Detoxification Pathways
In the liver, cysteine serves as a precursor for mercapturic acid synthesis, participating in sulfation detoxification of drugs (e.g., acetaminophen). When hepatic sulfur reserves are insufficient, L-alanyl-L-cystine supplementation enhances the activity of drug-metabolizing enzymes (e.g., UGT), reducing toxic metabolite accumulation.
IV. Immunomodulation and Inflammation Inhibition
Support for Immune Cell Function
Proliferation and differentiation of T cells and B cells depend on the antioxidant environment of GSH. L-alanyl-L-cystine enhances lymphocyte activation and cytokine (e.g., IL-2, IFN-γ) secretion by elevating intracellular GSH levels in immune cells. In immunodeficient mouse models, this dipeptide improves ConA-induced T cell dysfunction and restores immune responses.
Regulation of Inflammatory Signaling
Cystine metabolites inhibit the activation of nuclear factor κB (NF-κB) pathway, reducing the release of pro-inflammatory factors (TNF-α, IL-6). For example, in colitis models, L-alanyl-L-cystine alleviates intestinal epithelial cell damage and promotes mucosal repair by decreasing inflammatory factor levels in intestinal mucosa.
V. Functions in Special Physiological States
Support for Growth and Development
Infants have insufficient cystine synthesis capacity. As an exogenous sulfur source, L-alanyl-L-cystine promotes growth hormone secretion and protein synthesis. Studies show that adding this dipeptide to preterm infant formulas increases weight gain rate and nitrogen retention efficiency.
Exercise and Tissue Repair
During high-intensity exercise, muscle tissue generates abundant ROS. L-alanyl-L-cystine 减轻 muscle oxidative damage by supplementing GSH precursors, accelerating post-exercise recovery. Additionally, during wound healing, cysteine participates in collagen cross-linking, enhancing granulation tissue strength.
VI. Association with Metabolic Disorders and Diseases
Potential Application in Cystinuria
Cystinuria is a hereditary amino acid transport disorder where elevated urinary cystine concentration predisposes to stone formation. L-alanyl-L-cystine has higher intestinal absorption efficiency than free cystine, potentially reducing renal cystine excretion and stone risk (requiring further clinical validation).
Link to Metabolic Syndrome
Under insulin resistance, abnormal sulfur metabolism may exacerbate oxidative stress. L-alanyl-L-cystine enhances insulin sensitivity by improving GSH synthesis, with animal experiments showing amelioration of high-fat diet-induced obesity and glycemic abnormalities.
By decomposing into alanine and cystine, L-alanyl-L-cystine undertakes multiple physiological roles in the body, with core functions centered on sulfur metabolism, antioxidant defense, and energy balance. From cellular protection to systemic metabolic regulation, the physiological significance of this dipeptide is not only reflected in maintaining normal physiological states but also holds potential value in disease prevention (e.g., oxidative stress-related diseases, heavy metal poisoning) and nutritional support for special populations (preterm infants, athletes). Future research could focus on its mechanism of action in specific pathological models and optimize formulations and dose-response relationships as nutritional supplements.
