BCH 201 C.1, Course Outilne & Introduction 2022-2023 1.pdf

BCH 201: GENERAL BIOCHEMISTRY I General Course Outline:  Introduction to Biochemistry.  Molecular organization of cell; The cell theory.  Cell organelles of Prokaryotic and eukaryotic organisms.  Methods of cell fractionation. Centrifugation;  Structure and functions of intracellular organelle...

BCH 201: GENERAL BIOCHEMISTRY I General Course Outline:  Introduction to Biochemistry.  Molecular organization of cell; The cell theory.  Cell organelles of Prokaryotic and eukaryotic organisms.  Methods of cell fractionation. Centrifugation;  Structure and functions of intracellular organelles.  Cell constancy and diversity: Enzyme markers.  Chemical composition of cells – proteins, carbohydrates, lipids and nucleic acids.  WELCOME TO BIOCHEMISTRY  Lets know ourselves by names (Class rep?) Biochemistry and the Potential Future of a Biochemist: An introduction   What is an biochemistry?  Definitions:  1) Biochemistry is a hybrid science involved with the study of chemical reactions or processes taking place in living organisms.  It is neither pure biology nor pure chemistry, but a hybrid of both.  Biochemistry is different from ''Biology/Chemistry'' course which is taught in Colleges of Education.  2) Biochemistry (BCH) can also be defined as a science that explains life in molecular terms.  --Hence, the Motto of BCH department is 'Explaining Life in Molecular Terms'.  HISTORY OF BIOCHEMISTRY IN NIGERIA  The First Biochemist in Nigeria  Professor Olumbe Bassir is the foundation Professor and Head of Department of Biochemistry in Nigeria at the University of Ibadan, the first university in Nigeria.  The department started as a sub-department under the Department of Physiology at the University of Ibadan, with the then Dr. Olumbe Bassir (later Prof. O. Bassir) as sub-head in 1955 until 1960 when the department attained its full status. In 1962, a chair was created in the department and Dr. O. Bassir became the first Professor of the department. Various Aspects (Branches) of Biochemistry Medical Biochemistry Industrial Biochemistry Xenobiochemistry (Drug Toxicology) Food Biochemistry (Microbial Chemistry and Fermentation) Nutritional Biochemistry Molecular Biology/Bioinformatics Forensic Biochemistry Oncology (Cancer research) Plant Biochemistry Enzymology Membrane Biochemistry Biotechnology  Definition of Some Common Terms in Biochemistry  Metabolism  Metabolic Pathway (or simply, pathway) –This refers to a series of interconnected or linked chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes.  A + B ----> C ---> D + E  METABOLISM --- ANABOLISM AND CATABOLISM  Both catabolites or anabolites are generally referred to as metabolites.  METABOLITES (often used as a nickname among students or colleagues)  Common Examples of Metabolic Pathways include the following: (i) Glycolysis (also called Glycolytic pathway ) (ii) Glycogenolysis (iii) Gluconeogenesis (iv) Lipolysis (v) Pentose Phosphate Pathway (PPP) (vi) Purine biosynthetic pathway (vii)Pyrimidine biosynthetic pathway, etc.  Majority of Metabolic Pathways are Unidirectional Metabolic pathways are often considered to flow in one direction. Although all chemical reactions are technically reversible, conditions in the cell are often such that it is thermodynamically more favorable for flux to proceed in one direction of a reaction.  A + B ----> C ---> D + E For example, one pathway may be responsible for the synthesis of a particular amino acid, but the breakdown of that amino acid may occur via a separate and distinct pathway. One example of an exception to this "rule" is the metabolism of glucose through a process known as glycolysis. Glycolysis results in the breakdown of glucose, but several reactions in the glycolytic pathway are reversible and participate in the re-synthesis of glucose (a process called gluconeogenesis).  CYCLIC PATHWAY (OR CYCLE) Some metabolic pathways, or series of interconnected metabolic reaction steps, flow in a cyclic manner such that each component of the cycle is a substrate for the subsequent reaction step in the cycle. Such interconnected cyclic metabolic routes are called Cyclic pathways or Cycles. B A C F D Examples of metabolic cycles include: (i) Tricarboxylic acid cycle or TCA cycle (also known as Krebs’ Cycle) (ii) Urea cycle (iii) Cori cycle, etc.  COMPARTMENT: The word ‘compartment’ is simply used to refer to a specific part of an organ, tissue, cell or organelle in which a biochemical reaction or process takes place. Anabolic and catabolic pathways in eukaryotes often occur independently of each other, separated either physically by compartmentalization within organelles or separated biochemically by the requirement of different enzymes and co-factors.  FEEDBACK INHIBITION: This refers to a form of an enzyme inhibition or a reaction condition in which one of the products of the chemical reaction binds to an enzyme catalyzing a critical metabolic step in the reaction process, thereby terminating the reaction. Metabolic pathways are often regulated by feedback inhibition.  Definition of Some Common Terms in Biochemistry  Amino acids – Building blocks of proteins.  What are enzymes?  Most enzymes are proteinous in nature.  The 20 Common Amino acids and their Symbols 20 Common amino acids Versus ‘’the first 20 elements in Chemistry’’ Versus Homologous Series Hint: Note that the 20 common amino acids are not like ‘’the first 20 elements in Chemistry’’ which are usually arranged in order of increasing number of electrons, neither are they like ‘’members of a homologous series in Chemistry’’ that appear in their order of increasing carbon atoms. In Biochemistry, the 20 common amino acids simply refer to 20 amino acids that are commonly or usually found in all proteins.  The General Typical Structure of All Amino acids Typical Amino Acid (Zwitter ion form) (At neutral pH, amino acids assume a Zwitter ion form, Net charge = 0)  Classification of the 20 Common Amino acids  Structures and R group Classification of the 20 Common Amino acids  Structures of the 20 Common Amino acids  Structures of the 20 Common Amino acids  Structures of the 20 Common Amino acids  Protein Structures The shape or structure of a protein is very important to its function. To understand how a protein gets its final shape or conformation, there is need to understand the four levels of protein structure. Namely: 1.Primary Structure 2.Secondary Structure 3.Tertiary Structure and, 4.Quatenary Structure 1. Primary structure The simplest level of protein structure, known as the primary structure, is simply the sequence of amino acids in a polypeptide chain. The primary sequence do not reveal information about the conformation (arrangement in space) of the peptide chain—that is, whether the peptide chain is present as a long straight thread or is irregularly coiled and folded into a globule. For example, some parts of a peptide chain containing 100 to 200 amino acids may form a loop, or helix; others may be straight or form irregular coils. These forms of arrangement in space (spatial arrangement) are, however, not literally revealed by the sequence of amino acids in the protein molecule (primary structure). The primary structure of two polypeptide chains of the same protein may sometimes differ in total number of amino acid residues and/ or in the amino acid sequence within the peptide chains. For example, the hormone insulin has two polypeptide chains, A and B, shown in diagram below. (The insulin molecule shown here is cow insulin, although its structure is similar to that of human insulin.) Each chain has its own set of amino acids, assembled in a particular order. For instance, the sequence of the A chain starts with glycine at the N-terminus and ends with asparagine at the C-terminus, and is different from the sequence of the B chain. Figure: Primary structure of Cow insulin (which is similar to that of Human insulin). The sequence of a protein is determined by the DNA of the gene that encodes the protein (or that encodes a portion of the protein, for multi- subunit proteins). A change in the gene's DNA sequence may lead to a change in the amino acid sequence of the protein. Even changing just one amino acid in a protein’s sequence can affect the protein’s overall structure and function. For instance, a single amino acid change is associated with sickle cell anemia, an inherited disease that affects red blood cells. In sickle cell anemia, one of the polypeptide chains that make up hemoglobin, the protein that carries oxygen in the blood, has a slight sequence change. The glutamic acid that is normally the sixth amino acid of the hemoglobin β chain (one of two types of protein chains that make up hemoglobin) is replaced by a valine. This substitution is shown for a fragment of the β chain in the diagram below. A person whose body makes only sickle cell hemoglobin will suffer symptoms of sickle cell anemia. These occur because the glutamic acid-to- valine amino acid change makes the hemoglobin molecules assemble into long fibers. The fibers distort disc-shaped red blood cells into crescent shapes. 2. Secondary structure This is the next level of protein structure (secondary structure) and it refers to local folded structures that form within a polypeptide due to interactions between atoms of the backbone. (The polypeptide backbone just refers to the polypeptide chain apart from the R groups; which means that secondary structure does not involve R group atoms.) The most common types of secondary structures are the α-helix and the β-pleated sheet. Both structures are held in shape by hydrogen bonds, which form between the carbonyl O (carbonyl oxygen atom) of one amino acid and the amino H (amino hydrogen atom) of another amino acid.  Secondary structure of protein [also known as protein three-dimensional (3D) structure]. In an α-helix, the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-H) of an amino acid that is four down the chain. (E.g., the carbonyl of amino acid 1 would form a hydrogen bond to the N-H of amino acid 5.) This pattern of bonding pulls the polypeptide chain into a helical structure that resembles a curled ribbon, with each turn of the helix containing 3.6 amino acids. The R groups of the amino acids stick outward from the α-helix, where they are free to interact. In a β-pleated sheet, two or more segments of a polypeptide chain line up next to each other, forming a sheet-like structure held together by hydrogen bonds. The hydrogen bonds form between carbonyl and amino groups of backbone, while the R groups extend above and below the plane of the sheet. The strands of a β pleated sheet may be parallel, pointing in the same direction (meaning that their N- and C- termini match up), or antiparallel, pointing in opposite directions (meaning that the N-terminus of one strand is positioned next to the C- terminus of the other). Certain amino acids are more or less likely to be found in α-helices or β pleated sheets. For instance, the amino acid proline is sometimes called a “helix breaker” because its unusual R group (which bonds to the amino group to form a ring) creates a bend in the chain and is not compatible with helix formation. Proline is typically found in bends, unstructured regions between secondary structures. Similarly, amino acids such as tryptophan, tyrosine, and phenylalanine, which have large ring structures in their R groups, are often found in β pleated sheets, perhaps because the β pleated sheet structure provides plenty of space for the side chains. Many proteins contain both α helices and β pleated sheets, though some contain just one type of secondary structure (or do not form either type). 3. Tertiary structure The overall three-dimensional structure of a polypeptide is called its tertiary structure. The tertiary structure is primarily due to interactions between the R groups of the amino acids that make up the protein. R group interactions that contribute to tertiary structure include hydrogen bonding, ionic bonding, dipole-dipole interactions, and London dispersion forces – basically, the whole combination of non- covalent bonds. For example, R groups with like charges repel one another, while those with opposite charges can form an ionic bond (salt bridges). The bonds formed by the forces between the negatively charged side chains of aspartic or glutamic acid on the one hand, and the positively charged side chains of lysine or arginine on the other hand, are examples of salt bridges or ionic bonds. Similarly, polar R groups can form hydrogen bonds and other dipole-dipole interactions. Also important to tertiary structure are hydrophobic interactions, in which amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules. The type of attraction that exists between nonpolar side chains of valine, leucine, isoleucine, and phenylalanine is an example of hydrophobic interaction; the attraction results in the displacement of water molecules, hence the name hydrophobic interaction. Hydrogen bonds form as a result of the attraction between the nitrogen-bound hydrogen atom (the imide hydrogen, -NH) and the unshared pair of electrons of the oxygen atom in the double bonded carbon–oxygen group (the carbonyl group, -C=O). The result is a slight displacement of the imide hydrogen toward the oxygen atom of the carbonyl group. Although the hydrogen bond is much weaker than a covalent bond (i.e., the type of bond between two carbon atoms, which equally share the pair of bonding electrons between them), the large number of imide and carbonyl groups in peptide chains results in the formation of numerous hydrogen bonds. Finally, there’s one special type of covalent bond that can contribute to tertiary structure: the disulfide bond. Disulfide bonds, which are covalent linkages between the sulfur-containing side chains of cysteine residues, are much stronger than the other types of bonds that contribute to tertiary structure. They act like molecular "safety pins," keeping parts of the polypeptide firmly attached to one another. In proteins rich in cystine, the conformation of the peptide chain is determined to a considerable extent by the disulfide bonds (―S―S―) of cystine. The halves of cystine may be located in different parts of the peptide chain and thus may form a loop closed by the disulfide bond. If the disulfide bond is reduced (i.e., hydrogen is added) to two sulfhydryl (―SH) groups, the tertiary structure of the protein undergoes a drastic change—closed loops are broken and adjacent disulfide-bonded peptide chains separate. Tertiary structure of protein. 4. Quaternary structure Many proteins are made up of a single polypeptide chain (i.e one subunit) and have only three levels of structure (i.e the primary, secondary and tertiary). However, some proteins are made up of multiple polypeptide chains, also known as subunits. When these subunits come together, they give the protein its quaternary structure. A good example of a protein with quaternary structure is hemoglobin. Hemoglobin carries oxygen in the blood and is made up of four subunits, which belong to the α- and β- types of subunits (two each). Another example of a protein with quaternary structure is DNA polymerase, an enzyme that synthesizes new strands of DNA and is composed of ten subunits. In general, the same types of interactions that contribute to tertiary structure (mostly weak interactions, such as hydrogen bonding and London dispersion forces) also hold the subunits together to give the quaternary structure.  Continuation on Definition of Some Common Terms in Biochemistry  Enzymes – Definition and examples  Properties of enzymes.  KINDLY READ THROUGH THE NOTES PROVIDED IN MS WORD ON ENZYMES, NAMING, NAMES/PROPERTIES..  ATP (Adenosine 5‘-triphosphate)-- the major chemical form of energy used in living organisms for carrying out work or activities within the body such as to conduct biosynthesis of biomolecules, facilitate movement, and regulate active transport inside of the cell.  Significance of ATP and ADP levels in the body.  KINDLY REFER TO THE MS WORD NOTES FOR THE FOLLOWING:  SPECIAL FUNCTIONAL GROUPS IN AMINO ACIDS AND OTHER BIOMOLECULES  PEPTIDE BOND FORMATION  DETERMINATION OF MOLECULAR OF A POLYPEPTIDE CHAIN  SOME UNIQUE DERIVATIVES OF AMINO ACIDS AND THEIR RELEVANCE TO HEALTH  CLASSIFICATION OF AMINO ACIDS INTO ESSENTIAL, NON-ESSENTIAL, AND CONDITIONALLY ESSENTIAL CATEGORIES.  Biochemistry and the Potential Future of a Biochemist (Some Applications) A Biochemist can work in:  Pharmaceutical industries where drugs are produced either as part of the drug formulation/design research team or as a quality control personnel.  Crude Oil Companies such as NNPC, SPDC , Shevron, Exol Mobil , AGIP etc especially in aspects involving Bioremediation and Ecotoxicology.  Breweries where various drinks and beverages are produced e.g Coca- cola, Nigerian Brewing Company (NBC), La Casera Company, Bonvita Company etc.  Food industries where different kinds of food substances or confectionaries are produced (e.g Starch, Indomie, Sandine, Milkose, Tomtom producing companies etc).  Work in hospitals as Laboratory scientists, esp. in the unit of Clinical Chemistry, also called Chemical Pathology.  Working as Researchers in World Class Research Companies within & outside Nigeria (e.g IITA, NIFOR, INQUABA BIOTECH, NISER, FERMA, BIOTECH COMPANIES etc)  Many biochemists work hand in hand with Public health workers in various international NGOs dissipating information on disease incidence, prevention and treatments.  Universities within & outside Nigeria as Lecturers & Researchers that train future generation Biochemists etc.  A Biochemistry graduate can easily enrol for Medicine & Surgery after graduation. Recommended Textbooks for further insight  Lehninger Principles of Biochemistry by Nelson and Cox.  Textbook of Biochemistry with Clinical Correlations by Thomas M. Devlin.  Harper’s Biochemistry  Principles of Biochemistry by McKee and McKee.  Visit the Library for Encyclopædia ANY OTHER QUESTION? CLASS REP…………… MY ATTENDANCE LIST FOR TODAY OUR NEXT CLASS & TIME