BIOLOGICAL MOLECULES AND...

Genetica per Scienze Naturalia.a. 08-09 prof S. Presciuttini

BIOLOGICAL MOLECULES AND MACROMOLECULES

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1. Chemical composition of living cells

Approximate chemical compositions (percent of weight) Approximate chemical compositions (percent of weight) of a typical bacterium and a typical mammalian cellof a typical bacterium and a typical mammalian cell

COMPONENT Bacteria Mammalian cells

H2O 70 70Inorganic ions 1 1Small metabolites 3 3Proteins 15 18RNA 6 1.1DNA 1 0.25Lipids 2 5Polysaccharides 2 2

100 100

Total cell volume 2 × 10-12 cm3 4 × 10-9 cm3

Relative cell volume 1 2000


2. Four classes of macromolecules

All key components of every living cell are made of All key components of every living cell are made of macromoleculesmacromolecules. They can be classified into four main classes: . They can be classified into four main classes:

CarbohydratesCarbohydrates (sugars, starch and cellulose) (sugars, starch and cellulose) LipidsLipids (fats, oils, steroids) (fats, oils, steroids)ProteinsProteins (polypeptide chains and their assemblages) (polypeptide chains and their assemblages) Nucleic acidsNucleic acids (DNA and RNA) (DNA and RNA)

These macromolecules are made the same way in all living things, These macromolecules are made the same way in all living things, and they are present in all organisms in roughly the same and they are present in all organisms in roughly the same proportions; they make up what we visually recognize as lifeproportions; they make up what we visually recognize as life

Macromolecules are giant Macromolecules are giant polymerspolymers ( (polypoly means many; means many; mermer means units) constructed of many organic molecules called means units) constructed of many organic molecules called monomersmonomers. Some polymers are made of the same monomers, e.g. . Some polymers are made of the same monomers, e.g. cellulose, while others, e.g. proteins or nucleic acids, are made of cellulose, while others, e.g. proteins or nucleic acids, are made of a set of different monomers. Polymer chains can be linear, a set of different monomers. Polymer chains can be linear, branching or even circular.branching or even circular.


3. Functions of macromolecules Some of the roles of macromolecules are:Some of the roles of macromolecules are:

Energy storageEnergy storage CompartimentalizationCompartimentalization Structural supportStructural support CatalysisCatalysis TransportTransport Protection and defenseProtection and defense Regulation of metabolic activitiesRegulation of metabolic activities Maintenance of homeostasisMaintenance of homeostasis Means for movement, growth, and developmentMeans for movement, growth, and development HeredityHeredity

The functions of macromolecules are related to their shape and to The functions of macromolecules are related to their shape and to the chemical properties of their monomersthe chemical properties of their monomers


4. Chemical composition of biomoleculesHere is one way to think of the differences among macromolecule Here is one way to think of the differences among macromolecule classes: classes:

All carbohydrates such as wood or starch in every plant are made of just All carbohydrates such as wood or starch in every plant are made of just three chemical elements: three chemical elements: C, HC, H and and OO. (Some might also have small . (Some might also have small amounts of S and N.) amounts of S and N.)

All proteins of all organisms on earth are made of five chemical elements: All proteins of all organisms on earth are made of five chemical elements: C, H, O, N, SC, H, O, N, S. .

All nucleic acids of all organisms on earth are made of All nucleic acids of all organisms on earth are made of C, H, O, N, PC, H, O, N, P. . Here we see a uniformity of living organisms at the most elemental level. There is 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. 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 That is why all starches tend close-up to look alike (carrot or baobab), while proteins look startlingly different.proteins look startlingly different.Elements such as Elements such as C, H, O, N, PC, H, O, N, P and and SS (also called macro elements) make up (also called macro elements) make up biomolecules and are therefore the largest dry weight of all living organisms. 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 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 (e.g. the iron in hemoglobin, which carries oxygen, or the sodium and potassium ions that are responsible for nerve impulses.)ions that are responsible for nerve impulses.)


5. Monomers In living cells, a In living cells, a small setsmall set of monomers is used to create a variety of of monomers is used to create a variety of

polymers. Each polymer is unique in the number and type of polymers. Each polymer is unique in the number and type of monomers used to build it. monomers used to build it.

Macromolecule MonomersCarbohydrates monosaccharidesLipids glycerol, fatty acidsProteins amino acidsNucleic acid nucleotides


6. Monomers to polymers To qualify as a building block for polymers, each monomer must be capable of To qualify as a building block for polymers, each monomer must be capable of

linking with others. When a monomer's linking with others. When a monomer's functional groupfunctional group, a specific arrangement , a specific arrangement of atoms, reacts with a functional group of another monomer, the two molecules of atoms, reacts with a functional group of another monomer, the two molecules link together with a stable link together with a stable covalent bondcovalent bond, one that will not break under normal , one that will not break under normal conditions and will not dissolve in water.conditions and will not dissolve in water.


7. Sucrose, glucose, fructose

Example:Example: Sucrose (table sugar) is composed of glucose and fructose.Sucrose (table sugar) is composed of glucose and fructose.


8. Functional groups defined A functional group is a group of atoms of a particular arrangement that gives the 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 entire molecule certain characteristics. Functional groups are named according to the composition of the group. For example, COOH is a carboxyl group.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, 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 the diagram below can represent a carboxylic acid. The "R" can be any organic molecule.molecule.


9. The seven fundamental functional groups present in biological monomers


10. Twenty aminoacids and five nitrogen bases

The total number of biologically important monomers is The total number of biologically important monomers is surprisingly small, about 40-50, from which the thousands surprisingly small, about 40-50, from which the thousands of biologically important macromolecules are constructed.of biologically important macromolecules are constructed.

In particular, the set of amino acids common to all living In particular, the set of amino acids common to all living things includes 20 total different molecules, and the set of things includes 20 total different molecules, and the set of nitrogen bases that compose DNA and RNA include 5 nitrogen bases that compose DNA and RNA include 5 total different moleculestotal different molecules


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 .


12. Five different nitrogen bases

Nucleic acids (DNA and RNA) are linear polymers Nucleic acids (DNA and RNA) are linear polymers composed of monomers called nucleotides. The composed of monomers called nucleotides. The nucleotides are composed by a sugar, a phosphate nucleotides are composed by a sugar, a phosphate group, and an organic base. The base components group, and an organic base. The base components of nucleic acids are heterocyclic compounds with of nucleic acids are heterocyclic compounds with the rings containing nitrogen and carbon.the rings containing nitrogen and carbon.The bases adenine, guanine, and cytosine are found The bases adenine, guanine, and cytosine are found in both DNA and RNA; thymine is found only in in both DNA and RNA; thymine is found only in DNA, and uracil is found only in RNA. Adenine DNA, and uracil is found only in RNA. Adenine and guanine are purines, which contain a pair of and guanine are purines, which contain a pair of fused rings; cytosine, thymine, and uracil are fused rings; cytosine, thymine, and uracil are pyrimidines, which contain a single ring. pyrimidines, which contain a single ring. The bases are often abbreviated A, G, C, T, and U, The bases are often abbreviated A, G, C, T, and U, respectively. For convenience the single letters are respectively. For convenience the single letters are also used when long sequences of nucleotides are also used when long sequences of nucleotides are written out.written out.


13. Introducing metabolism Where do the building blocks (monomers) of the macromolecules in Where do the building blocks (monomers) of the macromolecules in

living cells come from?living cells come from?

METABOLISMMETABOLISM All living things must have an unceasing supply of energy and matter. The All living things must have an unceasing supply of energy and matter. The

transformation of this energy and matter within the body is called transformation of this energy and matter within the body is called metabolismmetabolismAnabolismAnabolism Anabolism is constructive metabolism. Typically, in anabolism, small Anabolism is constructive metabolism. Typically, in anabolism, small

precursor molecules, precursor molecules, oror metabolites, metabolites, are assembled into larger organic are assembled into larger organic molecules. This always requires the molecules. This always requires the inputinput of energy of energy

CatabolismCatabolism Catabolism is destructive metabolism. Typically, in catabolism, larger organic Catabolism is destructive metabolism. Typically, in catabolism, larger organic

molecules are broken down into smaller constituents. This usually occurs with molecules are broken down into smaller constituents. This usually occurs with the the releaserelease of energy of energy


CO2

14. Polymers, monomers, metabolites

Photosynthesis

Digestion

Respiration

Anabolism

Catabolism


The four “omic” biotechnologies of the new century Developments in high-throughput measurement technologies for biological molecules and Developments in high-throughput measurement technologies for biological molecules and

advancements in robotics and informatics have created a paradigm shift in modern life 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 science research. It is now possible to conduct and analyze simultaneous measurements of hundreds of thousands of individual experimental observations.hundreds of thousands of individual experimental observations.

As we enter the ‘post-genomic era’, ‘genome-wide’ expression profiling methods at the level 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 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 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, organisms (plants, animals and microbes) to probe unknown aspects of gene function, physiology and metabolism for a plethora of future research goals.physiology and metabolism for a plethora of future research goals.


GenomicsGenomics aims to understand the global structure of the Genomics aims to understand the global structure of the genomes, including mapping , including mapping the genes and sequencing the DNA. the genes and sequencing the DNA.

Structural genomics is the dissection of the architectural features of genes and is the dissection of the architectural features of genes and chromosomeschromosomes

Functional genomics refers to large-scale investigations of gene function refers to large-scale investigations of gene function For example, the way in which a cell responds to a particular signal or For example, the way in which a cell responds to a particular signal or

environmental stimulus can be monitored by simultaneously analysing the environmental stimulus can be monitored by simultaneously analysing the expression patterns of every single gene.expression patterns of every single gene.

Comparative genomics involves analysis of two or more genomes to identify involves analysis of two or more genomes to identify the extent of similarity of various features, or large-scale screening of a genome the extent of similarity of various features, or large-scale screening of a genome to identify sequences present in another genome.to identify sequences present in another genome.

For example, sequencing of the C. elegans genome permitted an evaluation of how 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 its genes compared with those of a simple eukaryote (S. cerevisiae) and a bacterium (E. coli).Comparative genomics -- the evolutionary relationships between the genes (E. coli).Comparative genomics -- the evolutionary relationships between the genes and proteins of different species. and proteins of different species.


Transcriptomics Transcriptomics, or global analysis of gene expression, also called genome-wide 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 expression profiling, is one of the tools that is used to get an understanding of genes and pathways involved in biological processes. and pathways involved in biological processes.

Transcription is the first step in gene regulation and information about the transcript Transcription is the first step in gene regulation and information about the transcript levels is needed for understanding gene regulatory networks. Thus, the new levels is needed for understanding gene regulatory networks. Thus, the new challenge is to identify all genes, their expression patterns and their function.challenge is to identify all genes, their expression patterns and their function.

The The transcriptome is the total collection of RNA transcripts in a cell. As more and is the total collection of RNA transcripts in a cell. As more and more genome sequences are being completed, new questions arise like more genome sequences are being completed, new questions arise like what are the functional roles of different genes and in what cellular processes what are the functional roles of different genes and in what cellular processes

do they participate,do they participate, how are genes regulated and how do genes and gene products interact,how are genes regulated and how do genes and gene products interact, how does gene expression levels differ in various cell types and stateshow does gene expression levels differ in various cell types and states and how is gene expression changed by various diseases or treatments.and how is gene expression changed by various diseases or treatments.


Proteomics Proteomics is devoted to the study of global changes in protein expression and the Proteomics is devoted to the study of global changes in protein expression and the

systematic study of protein-protein interactions.systematic study of protein-protein interactions. Proteomics focuses on the study of proteins : their roles, their structures, their Proteomics focuses on the study of proteins : their roles, their structures, their

localisation, their interactions, and other factors.localisation, their interactions, and other factors. Proteomics analyses, for example, the proteins of human fat cells , corn leaves, Proteomics analyses, for example, the proteins of human fat cells , corn leaves,

or an organism like the bacteria.or an organism like the bacteria. The The proteome designates all the proteins expressed by a genome. All the cells of an 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 organism contain the same genome, but their proteomes may differ depending on the organ and the stage of development of the individual.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, 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 tissue, and organ level. Thanks to modern protein analysis and separation techniques, and bioinformatics , it is possible to study thousands of proteins techniques, and bioinformatics , it is possible to study thousands of proteins simultaneously. Modern techniques make it possible to identify the protein – or the simultaneously. Modern techniques make it possible to identify the protein – or the interactions between different proteins - responsible for a human disease to develop, interactions between different proteins - responsible for a human disease to develop, for example, more precise and effective medical treatments; they can also identify 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 interesting and useful plant proteins, like those that give a plant resistance to drought.drought.


Metabolomics Metabolomics is the study of all of the small-molecule metabolites in a living 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 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, 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.diet and the environment on the health status of an individual.

Monitoring the Monitoring the metabolome is mostly based on the technologies of mass is mostly based on the technologies of mass spectrometry and nuclear magnetic resonance spectroscopy, which can detect and spectrometry and nuclear magnetic resonance spectroscopy, which can detect and measure hundreds of metabolites in one experiment.measure hundreds of metabolites in one experiment. These enable the effects of small alterations to the system to be measured, 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 seeing how they react to changes such as an altered diet or the introduction of a pesticide, drug or toxin.pesticide, drug or toxin.

The goal is to understand the metabolic state of a subject by extracting, identyfying 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) and quantifying all of the thouseands of small molecule coumpounds (metabolites) in a biological sample.in a biological sample. For example, metabolomic techniques have been used to identify perturbations For example, metabolomic techniques have been used to identify perturbations

in biochemical pathways associated with animal models of neurodegenerative in biochemical pathways associated with animal models of neurodegenerative disorders like Parkinson and Alzheimer disease in a range of brain tissues and disorders like Parkinson and Alzheimer disease in a range of brain tissues and cell cultures.cell cultures.

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