BCM 622 Enzymes and Proteins PDF

▪ Certain metal ions, including zinc, BCM 622 magnesium, and iron, affect the UNIT 3C: ENZYMES enzyme's structure and stability....

▪ Certain metal ions, including zinc, BCM 622 magnesium, and iron, affect the UNIT 3C: ENZYMES enzyme's structure and stability. Common Metal ions in enzymes STRUCTURE AND FUNCTIONS a. Mg2+ b. Zn2+ ENZYMES c. Fe2+ biological catalysts or biocatalysts speeds up a biochemical reaction without being a An enzyme lacking a cofactor or coenzyme is an reactant apoenzyme; an enzyme with a bound cofactor or catalysts for biochemical reactions in living systems coenzyme is a holoenzyme protein macromolecules that are necessary to initiate or speed up the rate of chemical reactions in the ENZYME STRUCTURE bodies of living organisms found in all living cells that vary in type based on the function it performs help in the process of digestion, blood clotting, and hormone production the molecules on which enzymes act are called MOST of the enzymes are proteins because some substrates, and the substance formed is called the enzymes are actually RIBOZYMES product o RIBOZYMES - RNA catalysts The enzyme is specific to its substrate. Towards the end of a reaction, the substrate is changed into a Found in all living cells product, and an enzyme-product complex is formed. o Ex. Digestion, blood clotting, protein The products can either be released from the active production site, or the reaction can occur in the reverse direction o FIBRINOGEN (inactive) - converted to FIBRIN (active) - which is involved in blood clotting TWO COMPONENTS/TYPES/CLASSES to form the original substrate again. ACTIVE SITE - site where the substrate reacts to the enzyme where it is binded Single enzymes - single chains Substrates or bigger - multiple chains Enzymes speed up chemical reactions, lower 1. Simple - proteins only activation energy 2. Conjugated o Enzymes increase the rate of reactions by a. Protein part (apoenzyme) - not yet complete lowering the Energy value. because has no non-protein, Apoenzyme - protein part only ARE ALL ENZYMES PROTEINS? b. Non-protein part (holoenzyme) - Holoenzyme - Almost all known enzymes are proteins. Whole - protein + non-protein part Previously it was believed that all enzymes are i. Organic (co-enzymes) - vitamins chemically protein in nature. needed in our body, particularly the B Then, certain nucleic acids known as ribozymes are complex B COMPLEX also found to have catalytic properties. - B1 - Thiamine pyrophosphate Students study protein-based enzymes when they - B2 – Riboflanin learn about this group of organic biomolecules. The - B3 – Niacin reason is that very little is known about ribozymes. - B5 - Pantoncenic acid Components - proteins are composed of long amino acids - B7 – Biotin chains that are held together by peptide bonds. Some enzymes - B9 - Folic acid (tetrahydrofalate) are made up of only one chain of amino acids, while most - B12 - Cobalamin) others are made of multiple chains. ▪ Required for proper enzyme Enzymes speed up the chemical reactions by function and are often derived from lowering the activation energy vitamins, e.g., NAD, NADH ii. Inorganic (co-factors) - Metal ions ▪ Metal ions bind to the enzyme's active site, contributing to its catalytic activity.  o Names: dehydrogenase, oxidase, oxygenase, reductase o ^^ 2 major clues to identify the reaction b) TRANSFERASES – TRANSFER of functional groups (e.g. amino or phosphate groups) between donor and acceptors NAMING AND CLASSIFICATION OF ENZYMES 1) TRIVIAL NAMES - Often names of the substrates with the suffix-ase added o Trypsin o Chymotrypsin o Ends in -in c) HYDROLASES – catalyze the hydrolysis of a o Some others end with -ase substrate (hydrolysis reaction) o HYDROLYSIS of substrates o Not all enzymatic reactions that have water is a hydrolase o Hint: the substance is SPLIT into two molecules o Splitting of larger molecule too two molecules 2) SYSTEMATIC NAMES – based on the reaction catalyzed (see below) d) LYASES – add or remove the elements of water, 6 SYSTEMATIC CLASSES OF ENZYMES ammonia or carbon dioxide to or from double bonds o Numbered according to enzyme cohesion o (synthase) - FORM or REMOVE DOUBLE number BONDS a) OXIDO-REDUCTASES - involved in oxidation and o add water, ammonia, or carbon dioxide - reduction removes double bond o oxidation and reduction, REDOX o remove these - form double bonds REACTIONS o NAD, NADH, FAD, FADH2 - hint to know if it is this class  Ex. Succinyltransferase - transferases Dihydrolase - hydrolases Transferase - transferases dehydrogenase - oxide-reductases Desuccinylase - hydrolases UNIT IV: NUCLEIC ACID – HOW STRUCTURE CONVEYS e) ISOMERASE – catalyze a change in the geometric or spatial configuration of a molecule (isomerization INFORMATION NUCLEIC ACIDS (NA): DNA AND RNA reactions) o REARRANGEMENT of configuration Repository of genetic information o Same number and identity of atoms but basic structural forms: changed SHAPE (geometric) or spatial 1. Deoxyribonucleic acid (DNA) configuration o genetic material o provides template for RNA transcription o stored in the Nucleic, rubric of life o Provides the template of transcription in RNA o Replicated during cell division (happens during S-phase) 2. Ribonucleic acid (RNA) o carriers of genetic information for protein translation o Synthesis of proteins (transcription and translation) f) LIGASES – synthetases; Join two molecules together o Carry and express genetic information at the expense of a high energy bonds o Adenine, cytosine, guanine, uracil (there is o (synthetases) - ATP or GTP - joining of 2 corresponding information) molecules MAJOR TYPES OF RNA 1. MRT - all transcript a. mRNA (messenger RNA) b. rRNA (ribosomal RNA) c. tRNA (transfer RNA) STRUCTURAL COMPONENTS AND ORGANIZATION OF NA NUCLEIC ACIDS - biopolymers of nucleotide ▪ made of polymers of nucleotides (divided into 3 main components) Basic components: Pentose sugar Heterocyclic Nitrogen bases Phosphate BASIC COMPONENTS OF NUCLEIC ACIDS Hetero (atoms present in the base are more than 1) Pentose sugar: Canonical Base pairs - rule of nature, only correct 5 carbon sugar base pairs o Structure of ribose is derived o Adenine & thymine - 2 hydrogen bonds o Beta-D-ribose is only found in RNA - 5 prime o Cytosine & Guanine - 3 hydrogen bonds o B-D-2’-deoxyribose o Base pairing of the bases are due to ▪ 2’ (indicate the position of the HYDROGEN BONDING absence of oxygen at the second o Glycosidic bonds - Responsible for the carbon) connect or linkage between bases or sugar ▪ pentose sugar (major difference Phosphate: between RNA and DNA) (in DNA it Nucleotide contains phosphate group is deoxyribose) o reason for acidic and anionic character Furan Attached to the 5’-carbon atom of the sugar component. β-D-2’-deoxyribose (β-D-2’-deoxyribofuranose) β-D-ribose (β-D-ribofuranose) sugar-phosphate linkages forms the symmetrical backbone of the nucleic acid with the 5’ end of one sugar always linked through a phosphate molecule to the 3’ end of the adjacent sugar Heterocyclic nitrogen base: Attached by a N-C glycosidic to the 1’-carbon atom of the sugar component Glycosidic bonds: o Purines: N9-C1’ glycosidic bonds ▪ 2 ring structures fused together, referring to only ADENINE & GUANINE Molecule or structure that gives the Nucleic acid its acidic and an ionic character o Pyrimidines: N1-C1’ glycosidic bonds 3 - triphosphate (ATP) —> 2 - diphosphate (ADP) —> ▪ CYTOSINE, THYMINE, URACIL 1 - momophosphate (AMP) —> phosphate (A) The formation of many phosphates creates disrupt phosphate anhydride bonds or pyrophosphate bonds (more than 1 phosphate group) Phosphodiester bond - bond (covalent) that links nucleotides with one another STRUCTURAL COMPONENTS AND ORGANIZATION OF NA Note: Purine bases glycosidic bonds are more susceptible to acid hydrolysis because of greater 5’ —> 3’ dipositivity 5 prime to 3 prime phosphodiester bond  o genetic material found in the nucleus INTERACTIONS RESPONSIBLE FOR NA RIGID o makes a copy of itself during cell division MOLECULAR CONFIGURATION (DNA biosynthesis, replication or duplication) Hydrogen bonds o provides template for RNA biosynthesis or o bonds between the complimentary base transcription pairs o anti parallel N-C glycosidic bonds o Sugar and phosphates are pointed outside o bonds between the bases and the sugars o DNA BIOSYNTHESIS o N9-C1’ in Purines and N1-C1’ in Pyrimidines ▪ During transcription, one strand of Phosphodiester bonds DNA is used as a template to o bonds between sugar and the phosphates transcribe DNA Van der Waal’s forces (pi-pi complexation) o Reverse Transcription - o base stacking – stacking interactions RNA can be converted back to DNA RIBONUCLEIC ACID (RNA): o transcribes the genetic information in DNA during RNA biosynthesis or transcription o carries and expresses genetic information transcribed via protein biosynthesis or translation in the ribosomes o RNA SYNTHESIS ▪ Can happen in RNA viruses ▪ Template for protein synthesis is based on RNA produced STRUCTURE OF NUCLEIC ACIDS Polymers of nucleotides, each composed of the: SUGAR – deoxyribose in DNA or ribose in RNA PHOSPHATE RESIDUE NITROGENOUS BASES (PURINE OR PYRIMIDINE BASE) o PURINE (Two ring structure) ▪ Adenine ▪ Guanine o PYRIMIDINES (Single ring structure) ▪ Cytosine ▪ Thymine (for DNA) ▪ Uracil (for RNA) UNIT IVB: NUCLEIC ACIDS – THE CENTRAL DOGMA OF MOLECULAR BIOLOGY NUCLEIC ACIDS (NA) A biomolecule vital to the development of a living being It is responsible for the storage and passage of genetic information for every cell, every tissue and organism needed for the production of proteins DNA stores genetic information for the development of a living being. o RNA expresses this information via transcription and translation to synthesize proteins NO NUCLEIC ACIDS, NO LIVING BEING NUCLEIC ACIDS ARE FOUND IN TWO BASIC STRUCTURAL FORMS: DEOXYRIBONUCLEIC ACID (DNA):  DNA STRUCTURE RNA STRUCTURE DNA REPLICATION Double stranded Single strand Anti-parallel Four different nucleotides Four different nucleotides A = adenine A = adenine T = thymine T = thymine C = cytosine C = cytosine G = guanine G = guanine Sugar – deoxyribose Sugar – ribose Phosphate Phosphate 1. Enzymes called helicases catalyze the unwinding of the DNA double helix o Unwinding - double stranded to single stranded (dsDNA - ssDNA) 2. SSB - Stabilize the single stranded structure (single stranded binding protein) 3. DNA replication is catalyzed by the DNA dependent DNA polymerase o Leading strand is synthesized continuously 4. 5’ —> 3’. Lagging strand is synthesized semi- discontinuously o Will create Okazaki fragments (5’-3’) 5. DNA ligaments - will connect the Okazaki o DNA polymerase fragments with one another TRANSCRIPTION NUCLEIC ACIDS (NA) Central dogma of molecular biology transfer of genetic information in the cell A: DNA Replication (Duplication) - DNA Biosynthesis B: Transcription - RNA Biosynthesis C: Reverse Transcription D: RNA Replication E: Translation - Protein Biosynthesis  1. INITIATION - state or phase where RNA transcription begins, recognition signals signal the cell to start production 2. ELONGATION - when RNA synthesis commences, starts forming new RNA 3. TERMINATION - when RNA signals the end of the process TRANSLATION 1. Initiation 2. Elongation 3. Termination IMPORTANCE OF NUCLEIC ACIDS 1. Understanding Genetics and Heredity: contain the genetic information determining an organism’s hereditary traits researchers can gain insights into how genes are inherited, how traits are passed down through generation variations in nucleic acid sequences contribute to genetic diversity and hereditary diseases molecular basis of heredity is found in the double helical nature of the DNA (considered as parent DNA) Ribosome (main organelle responsible for protein synthesis) o Mutations (not all mutations are reads mRNA one codon (sequence of 3 bases) at a time harmful) - ex. of genetic variations o 3 bases will be converted to protein o Traces of evolution or variation 2. Advancing Biotechnology and Genetic GENE EXPRESSION Engineering: a process where the information contained in genes manipulating nucleic acids in biotechnology begins to have effects in the cell and genetic engineering Genes are DNA sequences that encode proteins researchers can use techniques such as (the gene product) gene cloning, PCR (polymerase chain DNA encodes and transmits the genetic information reaction), and gene editing (e.g., CRISPR- passed down from parents to offspring Cas9) to modify nucleic acid sequences Genes - usual segment in DNA that are enabling the production of valuable proteins transcribed/synthesized during transcription development of genetically modified Must be sustained —> continuously and constantly organisms, and the treatment of genetic replicated disorders using microorganisms as alternative manufacturing (insulin) 3. Unraveling Disease Mechanisms: diseases, including various cancers, genetic disorders, and infectious diseases, have underlying molecular mechanisms that involve alterations in nucleic acid sequences scientists can identify disease-causing mutations by studying nucleic acids, developing diagnostic tests, and developing targeted therapies to treat these conditions Ex. Cancers 4. Advancing Medical Diagnostics: Nucleic acid-based techniques, such as the polymerase chain reaction (PCR) and DNA sequencing, are widely used in clinical diagnostics to detect pathogens, identify genetic variations, and diagnose inherited diseases These techniques play a critical role in personalized medicine by enabling tailored treatments based on an individual's genetic makeup 5. Understanding Evolution and Biodiversity: Comparative genomics and the study of nucleic acid sequences across different species provide insights into the evolutionary relationships between organisms By analyzing nucleic acid data, scientists can reconstruct evolutionary histories, trace the origins of various species, and understand the molecular mechanisms that underlie biodiversity. 6. Development of Therapeutics and Vaccines: Research on nucleic acids has led to the development of novel therapeutic approaches, such as mRNA vaccines and gene therapies These breakthroughs have revolutionized the fields of vaccine development and medical treatment, offering promising solutions for various diseases, including infectious diseases, genetic disorders, and certain types of cancer.