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BIOLOGICAL MOLECULES AND MACROMOLECULES This document is licensed under the Attribution-NonCommercial-ShareAlike 2.5 Italy license, available at http://creativecommons.org/licenses/by-nc-sa/2.5/it/ Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 1. Chemical composition of living cells Approximate chemical compositions (percent of weight) of a typical bacterium and a typical mammalian cell COMPONENT H2O Inorganic ions Small metabolites Proteins RNA DNA Lipids Polysaccharides Total cell volume Relative cell volume Bacteria Mammalian cells 70 70 1 3 15 6 1 2 2 100 1 3 18 1.1 0.25 5 2 100 2 × 10-12 cm3 1 4 × 10-9 cm3 2000 Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 2. Four classes of macromolecules All key components of every living cell are made of macromolecules. They can be classified into four main classes: Carbohydrates (sugars, starch and cellulose) Lipids (fats, oils, steroids) Proteins (polypeptide chains and their assemblages) Nucleic acids (DNA and RNA) These macromolecules are made the same way in all living things, and they are present in all organisms in roughly the same proportions; they make up what we visually recognize as life Macromolecules are giant polymers (poly means many; mer means units) constructed of many organic molecules called monomers. Some polymers are made of the same monomers, e.g. cellulose, while others, e.g. proteins or nucleic acids, are made of a set of different monomers. Polymer chains can be linear, branching or even circular. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 3. Functions of macromolecules Some of the roles of macromolecules are: Energy storage Compartimentalization Structural support Catalysis Transport Protection and defense Regulation of metabolic activities Maintenance of homeostasis Means for movement, growth, and development Heredity The functions of macromolecules are related to their shape and to the chemical properties of their monomers Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 4. Chemical composition of biomolecules Here is one way to think of the differences among macromolecule classes: All carbohydrates such as wood or starch in every plant are made of just three chemical elements: C, H and O. (Some might also have small amounts of S and N.) All proteins of all organisms on earth are made of five chemical elements: C, H, O, N, S. All nucleic acids of all organisms on earth are made of C, H, O, N, P. Here we see a uniformity of living organisms at the most elemental level. There is far less diversity in carbohydrates, which are made from just a few monomers. That is why all starches tend close-up to look alike (carrot or baobab), while proteins look startlingly different. Elements such as C, H, O, N, P and S (also called macro elements) make up biomolecules and are therefore the largest dry weight of all living organisms. Other elements are present in small numbers but can still play important roles (e.g. the iron in hemoglobin, which carries oxygen, or the sodium and potassium ions that are responsible for nerve impulses.) Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 5. Monomers In living cells, a small set of monomers is used to create a variety of polymers. Each polymer is unique in the number and type of monomers used to build it. Macromolecule Carbohydrates Lipids Proteins Nucleic acid Monomers monosaccharides glycerol, fatty acids amino acids nucleotides Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 6. Monomers to polymers To qualify as a building block for polymers, each monomer must be capable of linking with others. When a monomer's functional group, a specific arrangement of atoms, reacts with a functional group of another monomer, the two molecules link together with a stable covalent bond, one that will not break under normal conditions and will not dissolve in water. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 7. Sucrose, glucose, fructose Example: Sucrose (table sugar) is composed of glucose and fructose. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 8. Functional groups defined A functional group is a group of atoms of a particular arrangement that gives the entire molecule certain characteristics. Functional groups are named according to the composition of the group. For example, COOH is a carboxyl group. Organic chemists use the letter "R" to indicate an organic molecule. For example, the diagram below can represent a carboxylic acid. The "R" can be any organic molecule. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 9. The seven fundamental functional groups present in biological monomers Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 10. Twenty aminoacids and five nitrogen bases The total number of biologically important monomers is surprisingly small, about 40-50, from which the thousands of biologically important macromolecules are constructed. In particular, the set of amino acids common to all living things includes 20 total different molecules, and the set of nitrogen bases that compose DNA and RNA include 5 total different molecules Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 11. The 20 amino acids The amino acids are grouped into four categories according to the properties of their side chains: nonpolar, polar, basic, and acidic. Amino acids in a subclass are chemically similar. In general, polar amino acids are hydrophilic and nonpolar amino acids are hydrophobic, and this property has a large influence on the characteristics of the protein they constitute . Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 12. Five different nitrogen bases Nucleic acids (DNA and RNA) are linear polymers composed of monomers called nucleotides. The nucleotides are composed by a sugar, a phosphate group, and an organic base. The base components of nucleic acids are heterocyclic compounds with the rings containing nitrogen and carbon. The bases adenine, guanine, and cytosine are found in both DNA and RNA; thymine is found only in DNA, and uracil is found only in RNA. Adenine and guanine are purines, which contain a pair of fused rings; cytosine, thymine, and uracil are pyrimidines, which contain a single ring. The bases are often abbreviated A, G, C, T, and U, respectively. For convenience the single letters are also used when long sequences of nucleotides are written out. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 13. Introducing metabolism Where do the building blocks (monomers) of the macromolecules in living cells come from? METABOLISM All living things must have an unceasing supply of energy and matter. The transformation of this energy and matter within the body is called metabolism Anabolism Anabolism is constructive metabolism. Typically, in anabolism, small precursor molecules, or metabolites, are assembled into larger organic molecules. This always requires the input of energy Catabolism Catabolism is destructive metabolism. Typically, in catabolism, larger organic molecules are broken down into smaller constituents. This usually occurs with the release of energy Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 14. Polymers, monomers, metabolites Anabolism Photosynthesis CO2 Catabolism Respiration Digestion Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini The four “omic” biotechnologies of the new century Developments in high-throughput measurement technologies for biological molecules and advancements in robotics and informatics have created a paradigm shift in modern life science research. It is now possible to conduct and analyze simultaneous measurements of hundreds of thousands of individual experimental observations. As we enter the ‘post-genomic era’, ‘genome-wide’ expression profiling methods at the level of the transcriptome, proteome and the metabolome have come to the fore. This will allow a full and global comparison of the differences between cell types, tissues, organs and whole organisms (plants, animals and microbes) to probe unknown aspects of gene function, physiology and metabolism for a plethora of future research goals. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini Genomics Genomics aims to understand the global structure of the genomes, including mapping the genes and sequencing the DNA. Structural genomics is the dissection of the architectural features of genes and chromosomes Functional genomics refers to large-scale investigations of gene function For example, the way in which a cell responds to a particular signal or environmental stimulus can be monitored by simultaneously analysing the expression patterns of every single gene. Comparative genomics involves analysis of two or more genomes to identify the extent of similarity of various features, or large-scale screening of a genome to identify sequences present in another genome. For example, sequencing of the C. elegans genome permitted an evaluation of how its genes compared with those of a simple eukaryote (S. cerevisiae) and a bacterium (E. coli).Comparative genomics -- the evolutionary relationships between the genes and proteins of different species. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini Transcriptomics Transcriptomics, or global analysis of gene expression, also called genome-wide expression profiling, is one of the tools that is used to get an understanding of genes and pathways involved in biological processes. Transcription is the first step in gene regulation and information about the transcript levels is needed for understanding gene regulatory networks. Thus, the new challenge is to identify all genes, their expression patterns and their function. The transcriptome is the total collection of RNA transcripts in a cell. As more and more genome sequences are being completed, new questions arise like what are the functional roles of different genes and in what cellular processes do they participate, how are genes regulated and how do genes and gene products interact, how does gene expression levels differ in various cell types and states and how is gene expression changed by various diseases or treatments. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini Proteomics Proteomics is devoted to the study of global changes in protein expression and the systematic study of protein-protein interactions. Proteomics focuses on the study of proteins : their roles, their structures, their localisation, their interactions, and other factors. Proteomics analyses, for example, the proteins of human fat cells , corn leaves, or an organism like the bacteria. The proteome designates all the proteins expressed by a genome. All the cells of an organism contain the same genome, but their proteomes may differ depending on the organ and the stage of development of the individual. The proteomics gives you an overall view of the functions of a genome at the cell, tissue, and organ level. Thanks to modern protein analysis and separation techniques, and bioinformatics , it is possible to study thousands of proteins simultaneously. Modern techniques make it possible to identify the protein – or the interactions between different proteins - responsible for a human disease to develop, for example, more precise and effective medical treatments; they can also identify interesting and useful plant proteins, like those that give a plant resistance to drought. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini Metabolomics Metabolomics is the study of all of the small-molecule metabolites in a living system and how they react and interact. Metabolomics provides a biochemical signature that takes into account not only genetics, but also the effects of lifestyle, diet and the environment on the health status of an individual. Monitoring the metabolome is mostly based on the technologies of mass spectrometry and nuclear magnetic resonance spectroscopy, which can detect and measure hundreds of metabolites in one experiment. These enable the effects of small alterations to the system to be measured, seeing how they react to changes such as an altered diet or the introduction of a pesticide, drug or toxin. The goal is to understand the metabolic state of a subject by extracting, identyfying and quantifying all of the thouseands of small molecule coumpounds (metabolites) in a biological sample. For example, metabolomic techniques have been used to identify perturbations in biochemical pathways associated with animal models of neurodegenerative disorders like Parkinson and Alzheimer disease in a range of brain tissues and cell cultures. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini