Pharmacogenomics stands as one of the foundational pillars of Precision Medicine, aiming to understand how genetic variations among individuals influence their response to drugs. Biochemistry, on the other hand, is the science that studies molecular interactions within cells, including the structure of enzymes, proteins, receptors, and metabolic pathways. The relationship between these two fields is synergistic; biochemistry provides the molecular foundation for pharmacogenomics, while pharmacogenomics relies on understanding biological processes to explain interindividual variability in drug response. 1. The Molecular Basis of Pharmacogenomics and the Role of Biochemistry 1.1 Genes and Proteins Pharmacogenomics focuses on studying: · Genetic Polymorphisms · Mutations · Variations in Gene Expression These changes affect: · Protein structure · Protein Folding · Enzyme activity · Drug-receptor binding All of these are core topics in biochemistry. 1.2 Drug-Metabolizing Enzymes Biochemistry explains: · How a drug binds to an enzyme · How a drug is converted into metabolites · The effect of mutations on the enzyme's Active Site Key enzymes studied in pharmacogenomics include: · CYP450 family · UGT enzymes · NAT enzymes · TPMT Biochemistry elucidates how mutations lead to: · Increased enzyme activity · Decreased activity · Complete loss of function 2. The Role of Biochemistry in Understanding Drug Response 2.1 Metabolites Biochemistry studies: · The conversion of a drug from an inactive to an active form · The formation of toxic or safe metabolites · The effect of transporter proteins on drug movement This helps pharmacogenomics determine: · Why one person is sensitive to a specific drug? · Why another requires a higher dose? 2.2 Drug Receptors Biochemistry aids in analyzing: · The three-dimensional structure of a receptor · The Binding Site · The effect of mutations on binding affinity This is directly related to Pharmacodynamics. Example: A mutation in the β₁ receptor can affect the response to beta-blockers. 3. The Integration of Both Fields in Drug Metabolism Pathways 3.1 Phase I Metabolism Involves reactions such as: · Oxidation · Reduction · Hydrolysis These depend on CYP450 enzymes, whose structure and function are studied in biochemistry. 3.2 Phase II Metabolism Includes: · Glucuronidation · Sulfation · Methylation Influenced by mutations in enzymes like UGT1A1 and TPMT. Pharmacogenomics identifies the genetic variants. Biochemistry explains their effect on enzyme activity. 4. Gene-Drug Interaction Biochemistry explains: · How a single amino acid change can alter the function of an entire protein · Why metabolic rates differ between individuals · Why a drug causes toxicity in one person but is normally effective in another This is the essence of pharmacogenomics. 5. Shared Applications of Pharmacogenomics and Biochemistry 5.1 Personalized Medicine Through: · Genetic analysis · Understanding proteins and metabolic pathways · Knowing drug levels in the body It becomes possible to: · Determine the optimal drug dosage · Avoid toxicity · Improve treatment efficacy 5.2 Drug Development Pharmaceutical companies rely on: · A biochemical understanding of enzymes and receptors · Identifying common mutations among patients · Designing drugs suited to different genetic profiles 5.3 Treatment of Genetic Diseases Examples include: · G6PD deficiency · TPMT deficiency · CYP2C9 polymorphisms Here, biochemistry explains the effect of the mutation, while pharmacogenomics determines the appropriate treatment. 6. Future Challenges 1. The existence of thousands of mutations requiring precise biochemical explanations. 2. The difficulty of linking each mutation to its biological function. 3. The need to integrate genetic data with biochemical and clinical analyses. 4. The demand for experts skilled in both genetic and biochemical analysis. Conclusion Biochemistry provides the scientific basis for understanding genetic changes and their impact on proteins, enzymes, and receptors. Pharmacogenomics utilizes this information to interpret differences in patient drug responses. The integration of these two fields is essential for developing effective and safe treatments and for building the foundations of personalized medicine based on each individual's genetic makeup and biological functions. Al-Mustaqbal University - Ranked 1st Among Iraqi Private Universities