Chapter 3 Macromolecules of the Cell PDF

Chapter 3 Chapter 3 Macromolecules of the Cell The Macromolecules of the Cell Polymers are synthesized by condensation reactions in which activated monomers are linked together by the removal of water Most biological macromolecules in cells are synthesized from about 30 commo...

Chapter 3 Chapter 3 Macromolecules of the Cell The Macromolecules of the Cell Polymers are synthesized by condensation reactions in which activated monomers are linked together by the removal of water Most biological macromolecules in cells are synthesized from about 30 common small molecules Proteins Proteins are extremely important macromolecules in all organisms, occurring nearly everywhere in the cell Proteins fall into nine different classes Classes of proteins Enzymes function as catalysts, increasing the rates of chemical reactions Structural proteins - physical support and shape Motility proteins - contraction and movement Regulatory proteins - control and coordinate cell function Transport proteins - move substances in and out of cells Classes of proteins (continued) Hormonal proteins - communication between cells Receptor proteins - enable cells to respond to chemical stimuli from the environment Defensive proteins - protect against disease Storage proteins - reservoirs of amino acids The Monomers Are Amino Acids Only 20 kinds of amino acids are used in protein synthesis Some contain additional amino acids, usually the result of modification No two different proteins have the same amino acid sequence Amino acids Every amino acid has the same basic structure Each has a unique side chain, called an R group All amino acids except glycine have an asymmetric  carbon atom The specific properties of amino acids depend on the nature of their R groups Classes of R Groups Nine amino acids have nonpolar, hydrophobic R groups The remaining eleven amino acids are hydrophilic, with R groups that are either polar or charged at cellular pH Acidic amino acids are negatively charged, whereas basic amino acids are positively charged Polar amino acids tend to be found on the surfaces of proteins The Polymers Are Polypeptides and Proteins Amino acids are linked together stepwise into a linear polymer by dehydration (or condensation) reactions As the three atoms comprising the H2O are removed, a covalent C-N bond (a peptide bond) is formed Directionality of polypeptides Because of the way peptide bonds are formed, polypeptides have a directionality The end with the amino group is called the N- (or amino) terminus The end with the carboxyl group is called the C- (or carboxyl) terminus Proteins and polypeptides The process of elongating a chain of amino acids is called protein synthesis However, the immediate product of amino acid polymerization is a polypeptide A polypeptide does not become a protein until it has assumed a unique, stable three-dimensional shape and is biologically active Monomeric and multimeric proteins Proteins that consist of a single polypeptide are monomeric proteins, whereas multimeric proteins consist of two or more polypeptides Proteins consisting of two or three polypeptides are called dimers or trimers, respectively Hemoglobin is a tetramer, consisting of two  subunits and two  subunits Structure-function relationship Function is derived from structure Structure is derived from sequence Sickle-cell disease Normal red blood cells Sickle shaped red blood cells Due to single amino acid change in hemoglobin = protein carries oxygen in red blood cells Sickle-cell disease Sickle-cell disease Single specific amino acid change causes change in protein structure and solubility Results in change in cell shape Causes cells to clog blood vessels Several Kinds of Bonds and Interactions Are Important in Protein Folding and Stability Both covalent bonds and noncovalent interactions are needed for a protein to adopt its proper shape or conformation These same bonds and interactions are required for polypeptides to form multimeric proteins The interactions involve carboxyl, amino, and R groups of the amino acids, called amino acid residues once incorporated into a polypeptide Disulfide bonds Covalent disulfide bonds form between the sulfur atoms of two cysteine residues They form through the removal of two hydrogen ions (oxidation) and can only be broken by the addition of two hydrogens (reduction) Once formed, disulfide bonds confer considerable stability to the protein conformation Categories of Disulfide Bonds Intramolecular disulfide bonds form between cysteines in the same polypeptide Intermolecular disulfide bonds form between cysteines in two different polypeptides They link the two polypeptides together Noncovalent bonds and interactions These include hydrogen and ionic bonds, and van der Waals, and hydrophobic interactions These are individually weaker than covalent bonds but collectively can strongly influence protein structure and stability Hydrogen bonds Hydrogen bonds form in water and between amino acids in a polypeptide chain via their R groups Hydrogen bond donors (e.g., hydroxyl or amino groups) have hydrogen atoms covalently linked to more electronegative atoms Hydrogen bond acceptors (e.g., carbonyl or sulfhydryl groups) have an electronegative atom that attracts the donor hydrogen Ionic bonds Ionic bonds, or electrostatic interactions, form between positively and negatively charged R groups They exert attractive forces over longer distances than some of the other noncovalent interactions Because they depend on the charge on the R groups, changes in pH can disrupt ionic bonds Van der Waals interactions Molecules with nonpolar covalent bonds may have transient positively and negatively charged regions These are called dipoles and two molecules with these will be attracted to one another if they are close enough together This transient interaction is called a van der Waals interaction or van der Waals force Hydrophobic Interactions A hydrophobic interaction is the tendency of hydrophobic molecules or parts of molecules to be excluded from interactions with water Amino acids with hydrophobic side chains tend to be found within proteins Protein folding is a balance between the tendency of hydrophilic groups to interact with water and of hydrophobic groups to avoid interaction with water Protein Structure Depends on Amino Acid Sequence and Interactions The overall shape and structure of a protein are described in terms of four levels of organization – Primary structure - amino acid sequence – Secondary structure - local folding of polypeptide – Tertiary structure - three-dimensional conformation – Quaternary structure - interactions between monomeric proteins to form a multimeric unit Primary structure Primary structure is the formal designation of the amino acid sequence By convention, amino acid sequences are written from the N-terminus to the C-terminus, the direction in which the polypeptide was synthesized The first protein to have its amino acid sequence determined was the hormone insulin Insulin consists of one  and one  subunit with 21 and 30 amino acids, respectively Determining amino acid sequence Sanger obtained the Nobel Prize for his work on the insulin protein sequence He cleaved the protein into smaller fragments and analyzed the amino acid order within individual overlapping fragments Sanger’s work paved the way for the sequencing of hundreds of other proteins, and for advancements in the methods used for sequencing proteins The importance of primary structure Primary structure is important genetically because the sequence is specified by the order of nucleotides in the corresponding messenger RNA It is important structurally because the order and identity of amino acids directs the formation of the higher-order (secondary and tertiary) structures Secondary structure The secondary structure of a protein describes local regions of structure that result from hydrogen bonding between NH and CO groups along the polypeptide backbone These result in two major patterns, the  helix and the  sheet The  helix The  helix is spiral in shape, consisting of the peptide backbone, with R groups jutting out from the spiral There are 3.6 amino acids per turn of the helix A hydrogen bond forms between the NH group of one amino acid and the CO group of a second amino acid that is one turn away from the first The  sheet The  sheet is an extended sheetlike conformation with successive atoms of the polypeptide chain located at “peaks” or “troughs” The R groups jut out on alternating sides of the sheet Because of the formation of peaks and troughs, it is sometimes referred to as a -pleated sheet The β Sheet (continued) The β sheet is characterized by a maximum of hydrogen bonding, but β sheet formation may involve different polypeptides or different regions of a single polypeptide If the parts of polypeptides forming the β sheet have the same polarity (relative to the N- and C- termini), they are called parallel If the parts of polypeptides forming the β sheet have opposite polarity, they are called antiparallel Amino acid sequence and secondary structure Certain amino acids (e.g., leucine, methionine, glutamate) tend to form  helices whereas others (e.g., isoleucine, valine, phenylalanine) tend to form  sheets Proline cannot form hydrogen bonds and tends to disrupt  helix structures by introducing a bend in the helix Motifs Certain combinations of  helices and  sheets have been identified in many proteins These units of secondary structure consist of short stretches of  helices and  sheets and are called motifs Examples include the −−, the hairpin loop, and the helix-turn-helix motifs Tertiary structure The tertiary structure reflects the unique aspect of the amino acid sequence because it depends on interactions of the R groups Tertiary structure is neither repetitive nor easy to predict It results from the sum of hydrophobic residues avoiding water, hydrophilic residues interacting with water, the repulsion of similarly charged residues, and attraction between oppositely charged residues Native conformation The most stable possible three-dimensional structure of a particular polypeptide is called the native conformation Proteins can be divided into two broad categories – Fibrous proteins – Globular proteins Fibrous proteins Fibrous proteins have extensive regions of secondary structure, giving them a highly ordered, repetitive structure Some examples include – fibroin proteins of silk – keratin proteins of hair and wool – collagen found in tendons and skin – elastin found in ligaments and blood vessels Globular proteins Most proteins are globular proteins, that are folded into compact structures Each type of globular protein has its own unique tertiary structure Globular proteins may be mainly  helical, mainly  sheet, or a mixture of both Many globular proteins have domains A domain is a discrete locally folded unit of tertiary structure, usually with a specific function A domain is typically 50-350 amino acids long, with regions of  helices and  sheets packed together Proteins with similar functions often share a common domain Proteins with multiple functions usually have a separate domain for each function, like modular units from which globular proteins are constructed Prediction of tertiary structure It is known that primary structure determines the final folded shape of a protein However, we are still not able to predict exactly how a given protein will fold, especially for larger proteins Quaternary structure The quaternary structure of a protein is the level of organization concerned with subunit interactions and assembly Therefore, the term applies specifically to multimeric proteins Some proteins consist of multiple identical subunits; others, like hemoglobin, contain two or more types of polypeptides Maintenance of quaternary structure The bonds and forces maintaining quaternary structure are the same as those responsible for tertiary structure The process of subunit formation is usually, but not always, spontaneous Sometimes, molecular chaperones are required to assist the process Nucleic Acids Nucleic acids are of paramount importance to the cells because they store, transmit, and express genetic information They are linear polymers of nucleotides DNA is deoxyribonucleic acid, and RNA is ribonucleic acid DNA and RNA differ DNA and RNA differ chemically and in their role in the cell – RNA contains the 5-carbon sugar ribose, and DNA contains the related sugar, deoxyribose – DNA serves as the repository of genetic information, whereas RNA plays several roles in expressing that information RNA and polypeptide synthesis DNA resides mainly in the nucleus The nucleus is the major site of RNA synthesis – 1. Transcription: a segment of DNA known as a gene directs the synthesis of a complementary molecule of messenger RNA (mRNA) – 2. mRNA export: after processing, the mRNA exits the nucleus through tiny nuclear pores RNA and polypeptide synthesis (continued) Translation (polypeptide synthesis) takes place in the cytoplasm – 3. Translation: a ribosome, a complex of ribosomal RNA (rRNA) and proteins, attaches to the mRNA to read the coded information, whereas transfer RNA (tRNA) molecules bring the correct amino acids to add to the polypeptide chain Other types of RNA Several new types of RNA have been recently discovered – Most (or all) eukaryotic cells contain a variety of small RNAs (20-30 nucleotides long) that function as regulatory molecules – Micro RNAs (miRNAs), small, endogenous RNAs, down-regulate expression of specific genes – Other small interfering RNAs (siRNAs) come from exogenous sources, such as viruses, and can inhibit transcription or translation The Monomers Are Nucleotides RNA and DNA each consist of only four different types of nucleotides, the monomeric units Each nucleotide consists of a five-carbon sugar, to which a phosphate group and N-containing aromatic base are attached Each base is either a purine or a pyrimidine Types of nucleotides Purines are adenine (A) and guanosine (G) Pyrimidines are thymine (T) and cytosine (C), and in RNA, uracil (U) The sugar-base portion without the phosphate group is called a nucleoside Nomenclature Nucleosides with one phosphate group can be thought of as nucleoside monophosphates (example: adenosine monophosphate, AMP) Adenosine diphosphate (ADP) has two phosphate groups and adenosine triphosphate (ATP) has three The Polymers Are DNA and RNA Nucleic acids are linear polymers of nucleotides linked by a 3′,5′ phosphodiester bridge, a phosphate group linked to two adjacent nucleotides via two phosphodiester bonds The polynucleotide formed by this process has a directionality with a 5′ phosphate group at one end and a 3′ hydroxyl group at the other Nucleotide sequences are conventionally written in the 5′ to 3′ direction Nucleic acid synthesis A preexisting molecule is used to ensure that new nucleotides (NTPs for RNA, dNTPs for DNA) are added in the correct order This molecule is called a template and correct base pairing between the template and the incoming nucleotide is required to specify correct order A complementary relationship exists between certain purines and pyrimidines Complementary base pairing Complementary base pairing allows A to form two hydrogen bonds with T and G to form three hydrogen bonds with C This base pairing is a fundamental property of nucleic acids The DNA Molecule Is a Double- Stranded Helix Francis Crick and James Watson postulated the double helix structure of DNA in 1953 The structure accounted for the known physical and chemical properties of DNA It also suggested a mechanism for DNA replication The double helix consists of two anti-parallel and complementary strands of DNA twisted around a common axis to form a right-handed spiral structure (B-DNA, the main form in cells) Base pairing and RNA RNA is normally single stranded RNA structure also depends on base pairing However, the pairing is usually between bases in different areas of the same molecule and is less extensive than that of DNA Polysaccharides Polysaccharides are long chain polymers of sugars and sugar derivatives that are not informational molecules They usually consist of a single kind of repeating unit, or sometimes an alternating pattern of two kinds Short polymers, oligosaccharides, are sometimes attached to cell surface proteins The Monomers Are Monosaccharides Repeating units of polysaccharides are monosaccharides Sugars are often named generically based on how many carbon atoms they contain Classification of sugars Most sugars have between 3 and 7 carbons and are classified as – trioses (3 carbons) – tetroses (4 carbons) – pentoses (5 carbons) – hexoses (6 carbons) – heptoses (7 carbons) Glucose The single most common monosaccharide is the D-glucose (C6H12O6) The formula CnH2nOn is common for sugars and led to the general term carbohydrate The carbons of glucose (and other organic molecules) are numbered from the more oxidized, carbonyl, end Two ring forms of D-glucose The formation of a ring by D-glucose can result in two alternative forms These depend on the spatial orientation of the hydroxyl group on carbon number 1 These forms are designated  (hydroxyl group downward) and  (hydroxyl group upward) Glucose also exists as disaccharides Glucose exists as disaccharides, in which two monosaccharide units are covalently linked Common disaccharides include – maltose, (biotechnology) two glucose units – lactose, (milk) one glucose linked to one galactose – sucrose, (table sugar) one glucose linked to one fructose Disaccharides The linkage of disaccharides is a glycosidic bond, formed between two monosaccharides by the elimination of water Glycosidic bonds involving the  form of glucose are called  glycosidic bonds (e.g., maltose); those involving the  form are called  glycosidic bonds (e.g., lactose) The Polymers Are Storage and Structural Polysaccharides The most familiar storage polysaccharides are starch in plant cells and glycogen in animal cells and bacteria Both consist of -D-glucose units linked by - glycosidic bonds, involving carbons 1 and 4 (1→4) Occasionally (1→6) bonds may form, allowing for the formation of side chains (branching) Glycogen Glycogen is highly branched, the branches occurring every 8-10 glucose units along the backbone Glycogen is stored mainly in the liver (as a source of glucose) and muscle tissues (as a fuel source for muscle contraction) of animals Bacteria also store glycogen as a glucose reserve Starch Starch is the glucose reserve commonly found in plant tissue It occurs both as unbranched amylose (10- 30%) and branched amylopectin (70-90%) Amylopectin has (1→6) branches once every 12-25 glucose units, and longer side chains than glycogen Starch (continued) Starch is stored as starch grains within the plastids – Chloroplasts, the sites of carbon fixation and sugar synthesis in photosynthesis – Amyloplasts, which are specialized for starch storage Structural polysaccharides The best-known structural polysaccharide is the cellulose found in plant cell walls Cellulose, composed of repeating monomers of -D-glucose, is very abundant in plants Mammals cannot digest cellulose (some have microorganisms in their digestive systems that can) Other structural polysaccharides The cellulose of fungal cell walls differs from that of plants, and may contain either (1→4) or (1→3) linkages Bacterial cell walls contain two kinds of sugars GlcNAc (N-acetylglucosamine) and MurNAc (N-acetylmuramic acid) Both are derivatives of -glucosamine, and are linked alternately in cell walls Chitin The polysaccharide chitin consists of GlcNAc units only, joined by (1→4) bonds Chitin is found in insect exoskeletons, crustacean shells, and fungal cell walls Polysaccharide Structure Depends on the Type of Glycosidic Bonds Involved - and -glycosidic bonds are associated with marked structural differences Starch and glycogen ( polysaccharides) form loose helices that are not highly ordered due to the side chains Cellulose (that forms  linkages) exists as rigid linear rods that aggregate into microfibrils, about 5-20 nm in diameter Plant and fungal cells walls contain these rigid microfibrils in a noncellulose matrix containing other polymers (hemicellulose, pectin) and a protein called extensin Lipids Lipids are not formed by the same type of linear polymerization as proteins, nucleic acids, and polysaccharides However, they are regarded as macromolecules because of their high molecular weight and their importance in cellular structures, particularly membranes Features of lipids Although heterogeneous, all have a hydrophobic nature, and thus little affinity for water; they are readily soluble in nonpolar solvents such as chloroform or ether They have relatively few polar groups, but some are amphipathic, having polar and nonpolar regions Functions include energy storage, membrane structure, or specific biological functions such as signal transmission The main classes of lipids The lipids can be divided into six classes based on their structure – Fatty acids – Triacylglycerols – Phospholipids – Glycolipids – Steroids – Terpines Fatty Acids Are the Building Blocks of Several Classes of Lipids Fatty acids are components of several other kinds of lipids A fatty acid is a long amphipathic, unbranched hydrocarbon chain with a carboxyl group at one end The polar carboxyl group is the “head” and the nonpolar hydrocarbon chain is the “tail” Fatty acid structure (continued) In saturated fatty acids, each carbon atom in the chain is bonded to the maximum number of hydrogens These have long straight chains that pack together well Unsaturated fatty acids have one or more double bonds, so have bends in the chains and less tight packing Trans fats Trans fats are a type of unsaturated fatty acid with a particular type of double bond that causes less of a bend in the chain They are relatively rare in nature and are produced artificially in shortening and margarine They have been linked to increased risk of heart disease and elevated cholesterol levels Triacylglycerols Are Storage Lipids Triacylglycerols, also known as triglycerides, consist of a glycerol molecule with three fatty acids attached to it Glycerol is a three-carbon alcohol with a hydroxyl group on each carbon Fatty acids are linked to glycerol, one at a time, by ester bonds, formed by the removal of water Triacylglycerol function The main function of triacylglycerols is energy storage and some animals store triacylglycerols under the skin as a protection against cold Triacylglycerols containing mostly saturated fats are usually solid or semisolid at room temperature and are called fats Triacylglycerols in plants are liquid at room temperature (e.g., vegetable oil) and are predominantly unsaturated Phospholipids Are Important in Membrane Structure Phospholipids are important to membrane structure due to their amphipathic nature Phospholipids can be divided into phosphoglycerides or sphingolipids, depending on their chemistry Steroids Are Lipids with a Variety of Functions Steroids are derivatives of a four-ringed hydrocarbon skeleton, which distinguishes them from other lipids They are relatively nonpolar and therefore hydrophobic Steroids differ from one another in the positions of double bonds and functional groups The most common steroid in animal cells is cholesterol