Pharmaceutical Chemistry-IIA (Biochemistry) Lecture 1 PDF

PHARMACEUTICAL CHEMISTRY-IIA (BIOCHEMISTRY) Dr. Shaista Zafar  COURSE CONTENTS GENERAL INTRODUCTION AND BASIC BIOCHEMICAL PRINCIPLES ✔ Pharmaceutical biochemistry and role of Pharmaceutical Biochemistry in the health profession. Natur...

PHARMACEUTICAL CHEMISTRY-IIA (BIOCHEMISTRY) Dr. Shaista Zafar  COURSE CONTENTS GENERAL INTRODUCTION AND BASIC BIOCHEMICAL PRINCIPLES ✔ Pharmaceutical biochemistry and role of Pharmaceutical Biochemistry in the health profession. Nature of biochemical reactions BASIC CHEMISTRY OF BIOMOLECULES: (Nature, Classification etc.) ✔ Carbohydrates ✔ Proteins and amino acids ✔ Lipids ✔ Nucleic acid ✔ Vitamins ✔ Harmones ✔ Enzymes  Examination Pattern 1. Mid Term Exams 2. Final Exams 3. CP (Class Presentation/performance) (Assignments, Quiz, Presentations)  WHAT IS BIOCHEMISTRY ? Combination of chemistry and biology Investigate the chemistry (Biochemical process) of living systems The application of chemistry to the study of biological processes at the cellular /molecular level Study of the structure and behavior of the complex molecules and the ways these molecules interact to form cells, tissues and whole organism. Foundation for understanding of all biological processes in the body. A cell is made of molecules and a molecule is made of atoms. More complicated is that a cell is made up of macromolecules, such as proteins, lipids, etc. A molecule is a particular configuration of atoms  PRINCIPLES OF BIOCHEMISTRY Cells (basic structural units of living organisms) are highly organized Living processes contain thousands of chemical pathways. All organisms use the same type of molecules: carbohydrates, proteins, lipids & nucleic acids. Precise regulation and integration of pathways are required to maintain life A common pathway, Glycolysis is found in almost all organisms  PHARMACEUTICAL BIOCHEMISTRY The branch of biochemistry that studies how molecules in the body interact with drugs. It investigates the nature of binding between drugs and receptors and the cellular mechanisms of drug action. It is essential to improve human health, as it is the core of understanding and developing treatments that can improve lives. The application of biochemical laboratory methods in the diagnose, treatment and prevention of diseases  Role of Pharmaceutical Biochemistry in the health profession. Nature of biochemical reactions The chemical components of the human body Carbohydrates and lipids; amino acids and proteins; blood and plasma; biological membranes; nucleic acids (DNA and RNA) The major chemical processes in the human body Cell development; enzyme activity; membrane transport mechanisms; homeostasis; blood coagulation (clotting); oxygen transport; neurotransmitter function; ageing Nutrition and mineral metabolism, The role and function of vitamins in the body Molecular genetics Heredity Genomics  Therapeutic drug monitoring Biochemistry plays a critical role in patient care by providing valuable information for the diagnosis, monitoring, and treatment of diseases. The measurement of drug concentrations in the blood to ensure that patients receive the correct dosage of medication. This is particularly important for drugs with a narrow therapeutic window, where too little or too much of the drug can be harmful. Biochemistry plays a vital role in therapeutic drug monitoring, as it allows healthcare professionals to adjust dosages and ensure that patients receive the appropriate treatment. Therapeutic drug monitoring The measurement of specific drugs and/or their breakdown products (metabolites) at timed intervals to maintain a relatively constant concentration of the medication in the blood. Some of the monitored drugs tend to have a narrow “therapeutic index,” which is a ratio between the toxic and therapeutic (effective) dose of medication.  Biochemical markers Biomarkers are substances found in the body that can indicate the presence of a particular disease or condition. These markers are typically measured in blood, urine, or other bodily fluids and can provide important information about a person's health status Blood glucose is used to diagnose and monitor diabetes. Cholesterol, which can indicate an increased risk of heart disease if levels are too high. Enzymes, such as creatine kinase and lactate dehydrogenase, which can indicate tissue damage or disease Electrolytes, such as sodium and potassium, which can indicate imbalances in the body's fluid and electrolyte level All diseases have a molecular basis. It enables us to understand the chemical processes involved in disease conditions ✔ diabetes ✔ hyperammonemia ✔ hypo- and hyperparathyroidism ✔ jaundice ✔ kidney dysfunction ✔ hypercholesterolemia ✔ phenylketonuria ✔ sickle cell anaemia ✔ dental fluorosis ✔ rickets ✔ acidosis and alkalosis ✔ lysosomal storage diseases ✔ atherosclerosis Jaundice is a condition produced when excess amounts of bilirubin circulating in the blood stream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. Normal human physiological pH is 7.35 to 7.45. A decrease in pH below this range is acidosis, an increase over this range is alkalosis. Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Lysosomal storage diseases (LSDs) are rare genetic disorders caused by lack of enzymes. LSDs damage your body cells and organs. Atherosclerosis is thickening or hardening of the arteries caused by a buildup of plaque (fats/cholestrerol) in the inner lining of an artery Dental fluorosis is caused by taking in too much fluoride over a long period when the teeth are forming under the gums. Sickle cell anaemia is a severe hereditary form of anaemia in which a mutated form of haemoglobin distorts the red blood cells into a crescent shape at low oxygen levels  Biochemical reactions Chemical reactions that take place inside the cells are termed biochemical reactions. Inside a cell, a biochemical reaction is the transformation of one molecule into another. Biochemical reactions are mediated by enzymes that act as biological catalysts that can alter chemical reactions. Enzymes are biological catalysts, that may change the pace and specificity of chemical processes inside cells, and mediate biochemical reactions.  Types of biochemical reactions Isomerization reactions, ligation, hydrolysis, and oxidation-reduction reactions, condensation, and neutralization. There are two basic metabolic reactions anabolic and catabolic. Sometimes a third type is also defined, which is known as amphibolic pathways. Anabolic processes Endothermic reactions in organisms. Small/tiny molecules combine to form larger compounds Energy is required Example: The combining of amino acids to make a protein Catabolic reactions Exothermic processes in organisms Break down of large molecules into smaller pieces, releasing energy Example The breakdown of glucose is an of a catabolic reaction, which releases energy that cells require to carry out life functions. The respiratory route is an amphibolic pathway because it connects the synthesis (anabolic) and breakdown (catabolic) processes.  What is glycolysis? Glycolysis is the process in which glucose is broken down to produce energy This conversion is necessary for the production of ATP without which the cells cannot survive Glucose is a hexose sugar (monosaccharide with six carbon atoms and six oxygen atoms). It produces two molecules of pyruvate, ATP, NADH (nicotinamide adenine dinucleotide (NAD) + hydrogen) and water. The process takes place in the cytoplasm of a cell It occurs in both aerobic and anaerobic organisms. In glycolysis, 2 ATP molecules are consumed, producing 4 ATP, 2 NADH, and 2 pyruvates per glucose molecule. The pyruvate can be used in the citric acid cycle or serve as a precursor for other reactions.  ATP (Adenosine triphosphate) A ribose sugar attached to adenine and three phosphate molecules with high energy bonds. These bonds can be broken by hydrolysis and release energy. Universal energy carrier found in every cell of living organisms. Provide energy to all processes in living cells e.g. Muscle contraction, chemical synthesis etc. When consumed it converted to ADP (adenosine diphosphate) or AMP (adenosine monophosphate) ATP formed by oxidation reduction, condensation reactions Synthesis reactions Two or more reactants come together to form a more complex substance. Example, amino acids undergo a synthesis reaction when they join together to form a protein molecule. The majority of synthesis reactions are exothermic, (release energy in the form of heat). Hydrolysis is a chemical reaction in which the addition of water breaks down a polymer into its simpler monomer units. Example, peptides break into amino acids, carbohydrates into simple sugars, and DNA into nucleotides. Polysaccharides, such as starch, chitin, glycogen, and cellulose, can be broken down into monosaccharides by hydrolysis. This occurs through the process of hydrolysis, which uses water to break the bonds between monosaccharides.  Oxidation –Reduction Reaction Oxidation: loss of electrons Reduction: gain of electrons Redox used in cellular respiration Electrons removed from food molecules and transferred to another to produce energy An example is the oxidation of glucose during glycolysis where NAD+ is reduced, thereby, producing NADH. Conversion of glucose to carbon dioxide and water. Glucose is oxidized (losses electrons). Oxygen is the oxidizing agent, gaining electron. Energy released during reaction used by cells to perform various functions C6H12O6 + 6O 2 → 6CO2 + 6H 2O Redox reactions are common and vital to some of the basic functions of life, including photosynthesis, respiration, combustion, and corrosion or rusting.  References Payne JF, Fancey LL, Rahimtula AD, Porter EL (1987) Review and Perspective on the Use of Mixed-function Oxygenase Enzymes in Biological Monitoring. Comp Biochem Physiol Pt C 86:233–245. Biochemical Reactions. https://flexbooks.ck12.org/cbook/ck-12-biology- flexbook-2.0/section/1.14/primary/lesson/biochemical-reactions-bio/. Harper's Illustrated Biochemistry Thirty-First Edition Wilson and Walker's Principles and Techniques of Biochemistry and Molecular Biology Lippincott Illustrated Reviews: Biochemistry Edition: 8