Color--ChaptOneTwoFour.pdf

Dr. Karl Fath Office Hours – Wednesday 10 am — 12 pm Zoom (link on Blackboard) or in person (SB E-122) [email protected] Essential Cell Biology Sixth Edition Final exam date Electrons are not always shared equally and are closer to one atom than the other. •Polar vs. nonpolar •Polar molecules...

Dr. Karl Fath Office Hours – Wednesday 10 am — 12 pm Zoom (link on Blackboard) or in person (SB E-122) [email protected] Essential Cell Biology Sixth Edition Final exam date Electrons are not always shared equally and are closer to one atom than the other. •Polar vs. nonpolar •Polar molecules contain O,N,S,P •Nonpolar molecules contain C,H Things that I added after posting the slides See page 34 The Inner Life of the Cell Chapter 1: Cells: The fundamental units of life Basic properties of cells Different eukaryotic cells have the same organelles •differ in number, shape and distribution of organelles See Fig. 1-8 Eukaryotic cell cytoplasm is a crowded compartment Figure 1-25 Cytoplasm = organelles + cytosol A water-based gel Most people currently do not consider the nucleus to be a part of the cytoplasm Fig. 1.27 Much of what we know about cell biology comes from cultured cells -- a simpler system •Cells from Henrietta Lacks (HeLa) have been cultured since 1951 See Fig. 1-40 Relative sizes of cells and cell components •How big is a cell? •How big are its parts? Human egg ~150µm See Fig. 1-9 One mile (1.6km) Shrink 27,000 times Shrink 27,000 times Chapter 2: Chemical Components of Cells Basic Biological Chemistry Atoms are held together by bonds I. Covalent bonds Sharing of electrons II. Noncovalent bonds Polar vs. nonpolar Covalent Bonds •Strong (stronger than thermal energies of random collisions) •keep organic molecules together •broken using enzymes •Energy is stored in bonds and breaking bonds can release energy for useful work Figure 2-6,8 Electrons are not always shared equally and are closer to one atom than the other. More electronegative •Polar vs. nonpolar •Polar molecules contain O, N, S, P •Nonpolar molecules contain C, H Atoms are held together by bonds I. Covalent bonds Sharing of electrons II. Noncovalent bonds Polar vs. nonpolar Noncovalent interactions •relatively weak •not sharing of electrons, but attractive forces between atoms •imp. for folding macromolecules into proper shape (e.g., enzymes) •imp. for holding molecules together Noncovalent bonds hold molecules together by attractive forces between atoms of opposite charges — electrostatic attraction •attractions between molecules with polar, covalent bonds can form complementary charges •relatively weak and easily break and reform •although weak, many together can be strong (think of Velcro®) Figure 2-14 Four types of noncovalent bonds bring molecules together 1. Ionic bonds* 2. Hydrogen bonds 3. van der Waals attractions* 4. Hydrophobic force* *Due to time constraints, I will not discuss ionic bonds, van der Waals attractions and hydrophobic forces in class, but make sure that you are familiar with them. Four types of noncovalent bonds bring molecules together 1. Ionic bonds 2. Hydrogen bonds 3. van der Waals attractions 4. Hydrophobic force •Between bonded electronegative atom and bonded H atom •H is “sandwiched” between two electron-attracting atoms •H bonds form between most polar molecules and are especially important in the behavior of water. See Figure 2-13 Hydrogen bond formation between neighboring water molecules – Hydrogen bond formation between sugar and water See Panel 2-2 + Hydrogen Bonds • Partial charges between molecules attract each other and form hydrogen bonds. • Hydrogen bonds stabilize adjacent molecules to form arrays or crystals, e.g., water, or stabilize 3 dimensional configurations of large molecules, e.g., proteins. Importance of synthesis by polymerization of small molecules •most cellular structures (e.g., ribosomes, chromosomes, membranes) are made up by linear molecules (macromolecules) Four types of biological macromolecules 1. Carbohydrates (monosaccharides) 2. Lipids 3. Nucleic acids (nucleotides) 4. Proteins (amino acids) Macromolecules Polymers 1. Carbohydrates (monosaccharides) 1. Carbohydrates (monosaccharides) 2. Lipids 2. Nucleic acids (nucleotides) 3. Nucleic acids (nucleotides) 3. Proteins (amino acids) 4. Proteins (amino acids) Synthesis of macromolecules -- monomers and polymers Energetically unfavorable and so needs an energy source Lipids are macromolecules, but not polymers Condensation Hydrolysis aka “dehydration” reaction Fig 2-30, 31 02_33_macro complexes.jpg See Figure 2-36 Four types of biological macromolecules 1. Carbohydrates (monosaccharides) 2. Lipids 3. Nucleic acids (nucleotides) 4. Proteins (amino acids) Carbohydrates Forms -monosaccharides (monomer) -oligosaccharides (short polymer; 3–10 sugars) -polysaccharides (long polymer) Functions -chemical energy stored in covalent bonds is primary source of cell energy -sugar polymers are the most abundant structural components on earth Structure of monosaccharides (simple sugars) •Glucose is a key molecule in the metabolism of plants and animals Fig 2-18 03_40_2_Synthesis polymer.jpg Disaccharides -- 2 sugar units glycosidic bond (covalent) Sucrose (plant sap; table sugar) glucose + fructose Glucose Fructose Lactose (milk sugar) glucose + galactose Galactose Glucose See Panel 2-4 Polysaccharides -- many sugar units •imp. for energy storage and cell structure Four types of biological macromolecules 1. Carbohydrates (monosaccharides) 2. Lipids 3. Nucleic acids (nucleotides) 4. Proteins (amino acids) Lipids Forms (diverse structures; all mostly hydrophobic) -fats -steroids (sterols) -phospholipids Functions -energy storage (2X as much as carbohydrates). -membrane structure -specific biological functions Lipids Forms (diverse structures; all are mostly hydrophobic) 1. fats 2. phospholipids 3. steroids (sterols) 1. Fats Glycerol + Fatty acid = triacylglycerol •3 fatty acids esterified to glycerol •Storage form of fat in plants and animals fatty acid Fatty acid Hydrophilic Hydrophobic •saturated vs. unsaturated •amphipathic (polar/nonpolar) •size (usually even & 14 to 20 carbons) Panel 2-5 Fats •double bonds make kinks •the more double bonds the more liquid at RT •animal fats tend to be saturated •plants fats tend to be unsaturated and liquid (oil) •hydrogenate vegetable fat to make solid margarine •Storage form in plants & animals 2. Phospholipids •glycerol + 2 fatty acids + phosphate group bound to a polar group •amphipathic and make up the backbone of cell membranes 02_20_lipid membranes.jpg Fig. 2-23 3. Steroids (sterols) •characteristic 4 ring structure •cholesterol -membrane component -hormone precursor See Panel 2-5 Four types of biological macromolecules 1. Carbohydrates (monosaccharides) 2. Lipids 3. Nucleic acids (nucleotides) 4. Proteins (amino acids) Nucleic acids Forms •nucleotides (monomers) •nucleic acids (polymers)--RNA and DNA Functions •storage and transmission of genetic info •structure •catalytic Nucleotides -- nucleic acid monomers nucleosides 2 types of bases ribose; 5-carbons 2 types of sugars RNA--GCAU DNA --GCAT DNA - deoxyribonucleic acid RNA - ribonucleic acid See Panel 2-7 3’, 5’ phosphodiester bond 03_40_Synthesis polymer.jpg DNA functions •template for protein and RNA production •template for daughter cell genome Two chains of DNA molecules can H-bond to form DNA double-helix RNAs are usually single-stranded but can assume complex shapes • Although RNAs generally consist of single strands, they can fold back on themselves to form double-stranded segments • there are double-stranded RNA viruses • RNA functions 1. genetic information and transmission 2. catalytic enzymes -ribozymes 3. structure -- ribosome structure Four types of biological macromolecules 1. Carbohydrates (monosaccharides) 2. Lipids 3. Nucleic acids (nucleotides) 4. Proteins (amino acids) Chapter 4 Protein Structure and Function Proteins Forms •polymers of 20 different AA (amino acids) •unique arrangement of AA gives protein unique shapes allowing selective interactions •Typical cell may have 10,000 different proteins •Functions •Molecular tools and machines that perform nearly all the cell’s activities Reaction occurs on ribosomes in the cell Forming covalent peptide bond 03_40_3_Synthesis polymer.jpg See Fig 4-1 Four levels of protein structure 1. Primary Structure 2. Secondary Structure 3. Tertiary Structure 4. Quaternary Structure 1. Primary Structure Linear sequence of AA making up the polypeptide chain e.g., Arg-Gly-Asp-Ser (RGDS) •precise order of AA determined by genes •sequence determines protein shape •held together by peptide bonds •Changes in amino acid sequence caused by changes (mutations) in DNA Average protein in human genome contains ~100 aa Figure 4-3 •Once part of a polypeptide, an individual amino acid is called a residue •Side chains (aka R groups) give each AA its unique properties •side chains are not part of peptide bonds •even though the backbone amino and carboxyl are polar, the Hbond with each other and not with water, so the properties of the R-groups determines the hydrophobicity of the polypeptide Figure 4-2 Four levels of protein structure 1. Primary Structure 2. Secondary Structure 3. Tertiary Structure 4. Quaternary Structure 2. Secondary Structure •describes conformation (spatial organization) of polypeptide chain portions •formed between N-H and C=O of polypeptide backbone and doesn’t involve R-groups. Thus can be formed by many AA sequences (the identities of the R-groups, however, puts constraints on which type of conformations can form) • preferred ones provide maximum possible number of H–bonds between neighboring AA •there are two common conformations found in many proteins -- alpha(a) helix and beta (b) pleated-sheet Peptide “backbone” a-helix •cylindrical, twisting spiral H •H-bonds between AA of same molecule •peptide bonds of every 4th aa close •H-bonds parallel to cylinder axis •R-groups to outside •e.g., wool protein; can be stretched See Figure 4-12 a-helices can cross lipid bilayer 04_15_ahelix_lip_bilayer.jpg Figure 4-15 Sometimes 2-3 a-helices wrap around each other abcdefgabcdefgabcdefg •Intertwined a helices can form a coiledcoil •Heptad (7 aa repeat) •~ every 4th aa is hydrophobic and so a stripe of hydrophobic on inner surface Figure 4-16 •several polypeptide segments lie side-by-side; adopt folded or pleated conformation b-pleated sheet •H bonds perpendicular to molecule axis •e.g., silk protein; can’t be stretched H HOOC See Figure 4-13 H2N An example - Ribbon model of ribonuclease a b •In the average polypeptide, 60% of the chain is a-helix or bsheet •Chain portions not organized into a-helix or b-pleated sheet may consist of hinges, turns, loops •often most flexible portions of chain & sites of greatest biological activity Four levels of protein structure 1. Primary Structure 2. Secondary Structure 3. Tertiary Structure 4. Quaternary Structure 3. Tertiary Structure Makes up the conformation of the entire protein myoglobin •intramolecular noncovalent interactions between R groups in same chain •Fibrous proteins (highly elongated shape) - long strands or flattened sheets that resist pulling •Globular proteins – most proteins in the cell; compact shape; chains folded & twisted into complex shapes Noncovalent interactions between R groups in same polypeptide chain See Figure 4-4 Disulfide (—SS—) bridge •cysteine (—SH) group often covalently linked to another cysteine •helps stabilize protein structure Figure 4-30 •Protein folding is inherent in the molecule •may be sped up by accessory proteins Hydrophobic forces help proteins fold into compact conformations Figure 4-5 Cytochrome C Hydrophilic Hydrophobic Four levels of protein structure 1. Primary Structure 2. Secondary Structure 3. Tertiary Structure 4. Quaternary Structure 4. Quaternary Structure - the linking of polypeptide chains to form multisubunit functional protein (e.g., dimer, trimer or tetramer) •intermolecular R group interactions •subunits synthesized separately •may be linked by disulfide bonds, but more often noncovalent bonds Note: quaternary structure DOES NOT mean four subunits See Figure 4-24 Protein Organization Journal of Visualized Experiments (JoVE) Molecular chaperones •not all proteins assume proper tertiary or quaternary structure by self-assembly •interactions with other proteins may inhibit correct folding ATP required •chaperones help unfolded/misfolded proteins Figure 4-8 Protein vs. Polypeptide •Polypeptides --chains of AA •Proteins -- one or more polypeptides folded into a specific conformation; a functional molecule Protein domains (level of organization distinct from primary to quaternary; sometimes called “supersecondary structure”) •proteins often composed of 2 or more distinct modules (domains) that fold independently of one another (structurally or functionally) •often represent parts that function in semi-independent manner •part of a protein sequence that can function, evolve and exist independently of the rest of the protein chain •usually 25-500 AA in length Figure 4-20 Proteins are built of structural units (domains) •part of a protein sequence that can function, evolve and exist independently of the rest of the protein chain •usually 25-500 AA in length •multi-domain proteins probably evolved by the fusion of genes that once encoded separate proteins Conservation of protein domains over proteins of different families HOW PROTEINS ARE CONTROLLED • Many times the activity of proteins is controlled by altering the shape of the protein • Most proteins are allosteric; can adopt 2 or more conformations, which is regulated by something binding to its non- active site ADP regulates the activity of this hypothetical enzyme •ADP can only bind to closed conformation •Closed protein now more likely to bind substrate Figure 4-43 Protein phosphorylation can regulate protein activity Figure 4-44 Many GTP-binding proteins can be switched on/off by a gain/loss of a phosphate group Figure 4-46 Large conformational change protein synthesis enlongation factor releases tRNA when GTP à GDP GTP GDP Figure 4-40 3rd edition Cellular motors can use conformation change with ATP hydrolysis to move along a track Figure 4-48