Function of Abzymes and Diagnosis (summary)

Abzymes, or catalytic antibodies, function by lowering the activation energy of a reaction, making the transition state more achievable and allowing the reaction product to form. They combine the antigen-binding specificity of antibodies with the catalytic activity of enzymes, enabling them to target and catalyze specific chemical reactions.

Dominant Types of Abzymes in Immunoglobulins

The distribution of abzymes across different immunoglobulin classes (IgM, IgD, IgG, IgA, IgE) is not well-characterized in terms of dominance. Abzyme activity can potentially be engineered or naturally occurring in any of these classes, given that the defining feature of an abzyme is its catalytic ability rather than its class. However, IgG is the most studied and utilized class for creating catalytic antibodies due to its abundance and stability.

Difference Between an Enzyme and an Abzyme

• Enzymes are proteins that catalyze chemical reactions. They are highly specific to their substrates and can work under mild biological conditions to accelerate reactions by lowering activation energies.

• Abzymes are a type of enzyme made from monoclonal antibodies that have been engineered or naturally found to have catalytic activity. While they also lower activation energies of reactions, their uniqueness lies in their dual functionality: they can bind specific antigens (like antibodies) and catalyze chemical reactions (like enzymes).

Multi-Substrate System

A multi-substrate system involves reactions with more than one substrate. The complexity of these systems comes from the varied ways substrates can interact and bind, leading to different reaction sequences. Analyzing these systems is simplified by keeping one substrate at a constant concentration while varying the other, allowing for easier determination of reaction dynamics.

Alternative Names for Catalytic Antibodies

Catalytic antibodies are also known as abzymes, catmabs (catalytic monoclonal antibodies), and sometimes catabs. These terms highlight their nature as antibodies with enzymatic catalytic abilities.

Ribozymes and Abzymes

• Ribozymes are RNA molecules that exhibit catalytic activity, facilitating reactions such as RNA splicing and peptide bond formation in protein synthesis. They are essential for various biological processes.

• Abzymes are antibodies that have been engineered or naturally occur to possess enzymatic activity, enabling them to catalyze specific chemical reactions. They combine the specificity of antibodies with the catalytic function of enzymes.

Examples of Abzymes

Naturally occurring abzymes include anti-vasoactive intestinal peptide autoantibodies in normal individuals and DNAse abzymes in individuals with systemic lupus erythematosus (SLE), an autoimmune disease. These examples highlight the role of abzymes in both normal physiology and disease.

Sources of Abzymes

Abzymes are primarily artificial constructs but can also be found in human and animal serum. They occur in both healthy individuals and those with autoimmune diseases. Abzymes are capable of hydrolyzing a variety of biological molecules, including proteins, DNA, RNA, and polysaccharides.

Examples of Ribozymes

Examples of natural ribozymes include the hairpin, hammerhead, HDV, VS, and glmS ribozymes (small ribozymes), as well as group I and II introns, the ribosome, spliceosome, and RNase P (large ribozymes).

Types of Antibodies

Human antibodies are classified into five isotypes based on their heavy chains: IgM, IgD, IgG, IgA, and IgE. Each class has unique characteristics and roles within the immune system, with IgG being the most abundant in the bloodstream.

Why Abzymes Act as Catalysts

Abzymes act as catalysts because they possess the enzymatic ability to catalyze chemical reactions, lowering the activation energy needed for the reaction to proceed. This unique property allows them to target and modify specific molecules or pathogens, facilitating their elimination or modification in a way that traditional antibodies cannot.

Discovery of Abzymes

The concept of antibodies possessing catalytic activity was first proposed by Linus Pauling over six decades ago. The discovery and engineering of abzymes, particularly through the use of transition state analogs (TSAs) to induce the production of catalytic antibodies, have expanded significantly since the late 1980s.

Diagnosis:

The diagnosis of disorders associated with abzymes typically involves a combination of clinical evaluation, laboratory tests, and sometimes imaging studies. Key diagnostic steps include:

• Autoantibody Tests: Blood tests can detect the presence of specific autoantibodies (including abzymes) that target the body’s own tissues. Tests such as ANA (antinuclear antibody), RF (rheumatoid factor), and anti-CCP (cyclic citrullinated peptide) are common.
• Clinical Assessment: Symptoms and medical history play a crucial role in diagnosing autoimmune diseases. Physical examinations can reveal signs like joint swelling in RA or a butterfly rash in SLE.
• Imaging Tests: X-rays, MRIs, and ultrasounds can help assess the extent of organ or tissue damage, particularly useful in diseases like RA or MS.
• Functional Tests: Assessments of organ function, such as thyroid function tests or kidney function tests, can indicate the impact of abzymes on specific organs.

The identification of abzymes specifically as pathological agents often requires sophisticated laboratory techniques, including enzymatic assays or binding studies, to understand their role in disease processes.