Carbonylation is a widespread chemical modification affecting various molecules, particularly proteins. This process involves introducing a carbonyl group (C=O) into a molecule. It occurs in fundamental biological processes within living organisms and in the deterioration of food products. Understanding carbonylation provides insights into cellular health, disease progression, and the quality of consumables.
What is Carbonylation?
Carbonylation is a chemical reaction that introduces a carbonyl group (C=O) into a molecule. While carbonylation can involve the incorporation of carbon monoxide in industrial applications, in biological contexts, it largely refers to the oxidation of protein side chains. This process primarily targets the amino acid residues of proteins, such as lysine, arginine, proline, and threonine.
The formation of these carbonyl groups often results from oxidative stress, a state where there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them. ROS, such as free radicals, can directly react with proteins, leading to the formation of carbonyls. Carbonyls can also arise from the reaction of proteins with reactive carbonyl species (RCS), which are byproducts of lipid peroxidation or glycation. This chemical alteration can occur non-enzymatically, making it a common form of protein damage.
Carbonylation in Living Organisms
Within living organisms, carbonylation serves as an indicator of oxidative stress and affects the integrity and function of biological molecules. Proteins are particularly susceptible to this modification, with approximately 20-50% of cellular proteins potentially undergoing carbonylation under conditions of oxidative stress. This modification can alter a protein’s structure, leading to changes in its activity or even a complete loss of function.
Carbonylation can occur through various pathways, including direct oxidation of amino acid side chains by reactive oxygen species or through reactions with lipid peroxidation products. For instance, the oxidation of lysine residues can impact protein functionality and their susceptibility to degradation. While moderately carbonylated proteins can be degraded by the proteasomal system, heavily carbonylated proteins may form aggregates that resist degradation and accumulate within cells. These aggregates can further impair cellular processes and contribute to dysfunction.
Carbonylation and Disease
Carbonylation plays a role in the development and progression of various diseases and age-related conditions. The accumulation of carbonylated proteins is a well-established marker of oxidative damage and is frequently observed in aging tissues. This includes age-dependent cognitive decline, where oxidative modifications like protein carbonylation accumulate in the brain.
In neurodegenerative disorders, carbonylation contributes to cellular dysfunction and disease pathology. Elevated levels of carbonylated proteins are found in the brains of individuals with Alzheimer’s disease (AD) and Parkinson’s disease (PD). For example, studies have shown increased protein carbonyl content in the hippocampus and inferior parietal lobule of AD brains. Carbonylation of proteins involved in glucose metabolism, such as pyruvate kinase and creatine kinase, is also observed in mild cognitive impairment and advanced AD, suggesting altered energy metabolism as a shared mechanism in these conditions.
Carbonylation has also been linked to other chronic diseases. In type 1 diabetes, carbonylation contributes to the loss of activity of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), a protein involved in cardiac relaxation. This can lead to diastolic dysfunction, a common complication in diabetic patients. Increased protein carbonyl levels have also been found in patients with diabetes complications, suggesting their involvement in disease development.
Carbonylation’s Impact on Food
Beyond its biological implications, carbonylation affects the quality, safety, and nutritional value of food products. Proteins are major components of many foods, especially those from animal origin, and their carbonylation can lead to undesirable changes. This oxidative damage in food systems is often a result of radical-mediated mechanisms, though glyco-oxidation can also contribute significantly, particularly in the presence of reducing sugars.
The carbonylation of food proteins can lead to a loss of functionality and digestibility, impacting the overall nutritional value. For instance, it can alter the texture, flavor, and color of processed foods and beverages. Research indicates that protein carbonylation is linked to the deterioration of food quality, with studies showing increased protein carbonyls in refrigerated meats like pork loin over storage time. Understanding and mitigating carbonylation in food science is important for extending shelf life and maintaining product appeal.