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Transcript
BIO201 – Anatomy and Physiology I Biological Macromolecules Kamal Gandhi Lecture 2 Molecules • Very few elements are functional in the body in their inert, unchanged form • Most elements, instead, are found as ions or as parts of molecules • A molecule is the result of two or more atoms being bound together • Atoms form bonds in order to complete their valence shell of electrons SPONCH • The 6 SPONCH elements are vital for the formation of biological macromolecules because of their chemical bonding abilities • S • P • O • N • C • H Table 2-1 Biological Marcomolecules • The SPONCH elements make up the building blocks of cells – the 4 biological macromolecules – – – – Carbohydrates: short term energy storage Lipids: long term energy storage, membranes Proteins: cellular workhorse (functional part of a cell) Nucleic acids: genetic information (blueprint of a cell) • These macromolecules are long chains (polymers) built from small parts (monomers) Monomers and Polymers • Individual subunits are combined with each other to form large macromolecules • Water is directly involved in these reactions • Dehydration synthesis: a bond is formed by the removal of water • Hydrolysis: a bond is broken by the addition of water Fig. 5-2 HO 1 2 3 H Short polymer HO Unlinked monomer Dehydration removes a water molecule, forming a new bond HO 2 1 H 3 H2O 4 H Longer polymer (a) Dehydration reaction in the synthesis of a polymer HO 1 2 3 4 Hydrolysis adds a water molecule, breaking a bond HO 1 2 (b) Hydrolysis of a polymer 3 H H H2O HO H Carbohydrates • The primary molecule used by cells to make energy is carbohydrates • Contains a [C(H2O)]n motif • They can be used immediately to make ATP, the energy molecule of a cell • They can also be stored for “medium-term” in long chains or polymers • A few carbohydrates are more stable and are used as structural molecules • Carbohydrates typically contain carbonyl groups Fig. 5-3 Trioses (C3H6O3) Pentoses (C5H10O5) Hexoses (C6H12O6) Glyceraldehyde Ribose Glucose Galactose Dihydroxyacetone Ribulose Fructose Carbohydrates • The scientific name of carbohydrates are “saccharides” • A single unit of a saccharide is a monosaccharide • There are three common monosaccharides that are a part of your diet: glucose, fructose, and galactose • In a water environment (like a cell), these molecules will circularize into a ring structure at the carbonyl group Fig. 5-4a (a) Linear and ring forms Dissaccharides • In nature, the three monosaccharides combine into disaccharides that are common parts of your diet – Maltose: glucose + glucose, a common part of starchy foods – Lactose: galactose + glucose, a common part of dairy – Sucrose: glucose + fructose, aka table sugar Fig. 5-5 1–4 glycosidic linkage Glucose Glucose Maltose (a) Dehydration reaction in the synthesis of maltose 1–2 glycosidic linkage Glucose Fructose (b) Dehydration reaction in the synthesis of sucrose Sucrose Polysaccharides • Glucose is the primary sugar that almost all living organisms use for energy • When cells/organisms have extra glucose, they can store it for short/medium term • They do this by forming long chains of glucose – polysaccharides • In plants, longs chains of glucose are called starch • While starch is made by the plant to store glucose, starchy foods provide a large energy source in our diet • In humans/animals, long chains of glucose are called glycogen, and can be stored in the liver/muscles Fig. 5-6 Chloroplast Mitochondria Starch Glycogen granules 0.5 µm 1 µm Glycogen Amylose Amylopectin (a) Starch: a plant polysaccharide (b) Glycogen: an animal polysaccharide Structural polysaccharides • In a few cases, chains of glucose form more stable molecules that do not break down very easily • This is done by using an alternate form of glucose • The plant cell wall is made up of cellulose, a chain of β-glucose α vs β glucose • When glucose forms it’s ring structure, the bond at C1 can form in two orientations (“up” vs “down”) • The version that cells use for energy is the “down” orientation – α glucose • Some organisms are able to make the “up” orientation as well – β glucose • Since most organisms do not have the enzymes needed to breakdown β glucose, it is used as a stable, structural molecule in plants (cellulose) • Because we cannot breakdown β-glucose, this version passes through the body unchanged - fiber Fig. 5-7a Glucose (a) and glucose ring structures Glucose Fig. 5-7bc (b) Starch: 1–4 linkage of glucose monomers (c) Cellulose: 1–4 linkage of glucose monomers Fig. 5-8 Cell walls Cellulose microfibrils in a plant cell wall Microfibril 10 µm 0.5 µm Cellulose molecules Glucose monomer Lipids • One of the most stable macromolecules are fats • Because they are so stable, fats (lipids) can be used for long-term energy storage • A second, more important function of lipids in a cell is that they are used to make cellular membranes • There are two alternate forms of lipids that are utilized for these functions – triglycerides and phospholipids • A third, minor lipid in nature, though a very important one for cells, are steroids, which are used to stabilize membranes and for hormones Triglycerides • The form of fat that we use for long-term energy storage (and to provide cushioning to organs, insulation to the body, etc) is a triglyceride • The “glyceride” part refers to the central sugar molecule, a 3-C molecule called glycerol • The “tri” part refers to the 3 fatty acids that are attached to the glycerol, one to each carbon • These fatty acids are long hydrocarbon chains that are non-polar, making fats hydrophobic so they don’t dissolve in water Fig. 5-11a Fatty acid (palmitic acid) Glycerol (a) Dehydration reaction in the synthesis of a fat Fig. 5-11b Ester linkage (b) Fat molecule (triacylglycerol) Fatty acids • One end of the fatty acid contains a carboxyl group, allowing it to bind to the glycerol • The hydrocarbon tail of a fatty acid can be of varying length, typically 14-, 16-, or 18-C long • The fatty acid tail is only made up of C and H; but occasionally some of the Cs form double bonds • In a saturated fat, there are no double bonds, and the fat is therefore saturated with the maximum Hs • In an unsaturated fat, there is a double bond, and so there are less than the maximum number of Hs Fig. 5-12a Structural formula of a saturated fat molecule Stearic acid, a saturated fatty acid (a) Saturated fat Fig. 5-12b Structural formula of an unsaturated fat molecule Oleic acid, an unsaturated fatty acid (b) Unsaturated fat cis double bond causes bending Fats • A saturated fat will allow the fat molecules to align closer together, making these fats solid (at room temp) • An unsaturated fatty acid will have a kink in the tail; which prevents close packing of these fats, and so they tend to be liquid (at room temp) • Unsaturated fats can be mono- (one double bond) or poly(multiple double bonds) unsaturated • A hydrogenated fat (like margarine) is an unsaturated fat to which H has been added, causing it to lose its double bond (which can be bad for you if it happens incorrectly) Phospholipids • The second major class of fat molecules are phospho-lipids, which are used for virtually all cell membranes • In these molecules, one of the fatty acids is replaced with a phosphate group (PO4), which has a negative charge and is therefore hydrophilic • The phospholipid therefore has a hydrophilic head region (the glycerol and phosphate) and a hydrophobic tail region (the 2 remaining fatty acids) • Because it it amphipathic, phospholipds will form a bilayer structure in water (discussed more next lecture) Hydrophobic tails Hydrophilic head Fig. 5-13ab (a) Structural formula Choline Phosphate Glycerol Fatty acids (b) Space-filling model Fig. 5-14 Hydrophilic head Hydrophobic tail WATER WATER Steroids • The third type of lipid is a steroid molecule • In cells, steroids (sterols/cholesterols) are important for maintaining stability as temperatures change • Furthermore, in our body, steroids serve as a major class of hormone Fig. 5-15 Fig. 7-5c Cholesterol (c) Cholesterol within the animal cell membrane Proteins • The protein is the most important part of a cell, because it provides that cell with all of its functional ability • Proteins can be described as our cellular workhorse • It carries out all of the functions of a cell, including structure, movement, support, signaling, and enzymes • Proteins are chains of amino acids, linked together by peptide bonds • The function of an individual protein is based on its structure, and the structure is based on the sequence of these amino acids Table 5-1 Amino acids • There are 20 naturally occurring amino acids in nature • All amino acids share the same overall structure, with a central Carbon bound to an amino group, a carboxyl group, and a Hydrogen • The 4th bond of the central carbon is to a variable side group, called the R group • The chemical characteristics of the R group gives individual amino acids their different characteristics Fig. 5-UN1 carbon Amino group Carboxyl group Fig. 5-17 Nonpolar Glycine (Gly or G) Valine (Val or V) Alanine (Ala or A) Methionine (Met or M) Leucine (Leu or L) Trypotphan (Trp or W) Phenylalanine (Phe or F) Isoleucine (Ile or I) Proline (Pro or P) Polar Serine (Ser or S) Threonine (Thr or T) Cysteine (Cys or C) Tyrosine (Tyr or Y) Asparagine (Asn or N) Glutamine (Gln or Q) Electrically charged Acidic Aspartic acid (Asp or D) Glutamic acid (Glu or E) Basic Lysine (Lys or K) Arginine (Arg or R) Histidine (His or H) Peptide bonds • Amino acids are linked together by peptide bonds into long chains to make functional proteins • A peptide bond is a repeatable bond formed between the carboxyl group of one amino acid and the amino group of the next amino acid • Because this leave another free carboxyl group, another amino acid can be added downstream • As this process continues, it creates a direction to proteins; the N-terminus (front end) and C-terminus (back end) Fig. 5-18 Peptide bond (a) Side chains Peptide bond Backbone (b) Amino end (N-terminus) Carboxyl end (C-terminus) Polypeptides • As amino acids grow longer, they will start to fold into a 3dimensional structure • This structure determines the function of the protein • We typically define 4 different levels of protein structure – Primary: the sequence of amino acids – Secondary: folding into α-helices and β-pleated sheets, caused by H-bonding of the backbone – Tertiary: folding of the polypeptide caused by interactions between side groups (disulfide bridges between cysteine, H bonds, ionic bonds, van der Waals interactions) – Quarternary: interactions between multiple polypeptides Fig. 5-21a Primary Structure 1 5 H3N Amino end + 10 Amino acid subunits 15 20 25 Fig. 5-21c Secondary Structure pleated sheet Examples of amino acid subunits helix Fig. 5-21f Hydrophobic interactions and van der Waals interactions Polypeptide backbone Hydrogen bond Disulfide bridge Ionic bond Fig. 5-21e Tertiary Structure Quaternary Structure Fig. 5-21g Polypeptide chain Chains Iron Heme Chains Hemoglobin Collagen Structure determines function • The 3D structure of a protein is vital to determining its function • Typically because the structure affects the interactions of the protein with other molecules • Protein structure can be altered by changing the chemical environment (pH) or the physical environment (temperature), causing proteins to denature (unfold) • Sometimes, changing just one amino acid can cause the protein to misfold, creating the wrong structure and a partially or non-functional protein Fig. 5-19 Groove Groove (a) A ribbon model of lysozyme (b) A space-filling model of lysozyme Fig. 5-22 Normal hemoglobin Primary structure Val His Leu Thr Pro Glu Glu 1 2 3 4 5 6 7 Secondary and tertiary structures subunit Function Normal hemoglobin (top view) Secondary and tertiary structures 1 2 Normal red blood cells are full of individual hemoglobin moledules, each carrying oxygen. 5 6 7 subunit Sickle-cell hemoglobin Function Molecules interact with one another and crystallize into a fiber; capacity to carry oxygen is greatly reduced. 10 µm Red blood cell shape 4 Exposed hydrophobic region Molecules do not associate with one another; each carries oxygen. 3 Quaternary structure Val His Leu Thr Pro Val Glu Quaternary structure Sickle-cell hemoglobin Primary structure 10 µm Red blood cell shape Fibers of abnormal hemoglobin deform red blood cell into sickle shape. Enzymes • Perhaps the most important function of proteins in a cell is to serve as a biological catalyst (enzymes) • A catalyst is a molecule that speeds up chemical reactions without being changed by the reaction • It speeds up the reaction by requiring less energy • All chemical reactions that take place in a cell require enzymes in order to occur under Fig. 5-16 Substrate (sucrose) Glucose Enzyme (sucrase) OH Fructose H O H2O Nucleic acids • Nucleic acids serve as genetic information for a cell • This genetic information comes in two forms, DNA (permanent copy) and RNA (temporary copy) • They provide the information necessary to maintain and reproduce a cell • They are also passed from the mother cell to the two daughter cells during cell division; or from parent to offspring during reproduction Nucleic acids • The permanent blueprint stored by a cell is DNA • The sequence of DNA is called the genome, and it contains the information to make all of the proteins the cell/organism might ever need • The code for one individual protein is called a gene • That gene gets transcribed into RNA, a temporary copy of the blueprint for one Fig. 5-26-3 DNA 1 Synthesis of mRNA in the nucleus mRNA NUCLEUS CYTOPLASM mRNA 2 Movement of mRNA into cytoplasm via nuclear pore Ribosome 3 Synthesis of protein Polypeptide Amino acids DNA • DNA is a double helix of anti-parallel strands held together by H-bonds between base pairs • Each strand is a polymer of nucleotides • A nucleotide consists of a sugar, a phosphate, and a Nitrogenous base • The sugar and phosphate make up the backbone of each DNA strand • The N-base sticks inside the backbone and makes up the “rungs of the ladder” Fig. 16-7a 5 end Hydrogen bond 3 end 1 nm 3.4 nm 3 end 0.34 nm (a) Key features of DNA structure (b) Partial chemical structure 5 end Fig. 5-27 5 end Nitrogenous bases Pyrimidines 5C 3C Nucleoside Nitrogenous base Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA) Purines Phosphate group 5C Sugar (pentose) Adenine (A) Guanine (G) (b) Nucleotide 3C Sugars 3 end (a) Polynucleotide, or nucleic acid Deoxyribose (in DNA) (c) Nucleoside components: sugars Ribose (in RNA) DNA vs RNA • DNA is double stranded, whereas RNA is single stranded • DNA uses deoxyribose as the central sugar, whereas RNA uses ribose • The 4 bases in DNA are A, C, G, and T • The 4 bases in RNA are A, C, G, and U Fig. 5-27ab 5' end 5'C 3'C Nucleoside Nitrogenous base 5'C Phosphate group 5'C 3'C (b) Nucleotide 3' end (a) Polynucleotide, or nucleic acid 3'C Sugar (pentose) Fig. 5-27c-2 Sugars Deoxyribose (in DNA) (c) Nucleoside components: sugars Ribose (in RNA) Fig. 5-27c-1 Nitrogenous bases Pyrimidines Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA) Purines Adenine (A) Guanine (G) (c) Nucleoside components: nitrogenous bases Nucleic acids • DNA and RNA serve as genetic information they are the blueprint to make proteins • Protein function is based on structure, which is based on the sequence of amino acids • DNA serves as a blueprint for proteins through the sequence of bases that make up an individual gene • Through the genetic code, the sequence of bases gets translated into the sequence of amino acids to make up different proteins Third mRNA base (3 end of codon) First mRNA base (5 end of codon) Fig. 17-5 Second mRNA base Chromosomes • The human genome consists of 3 Gbp of DNA • If unwound, this makes up 6 feet of DNA that must fit into each and every cell of the body • Therefore, DNA in a cell cannot be allowed to completely unwind • Instead, in a cell DNA is wrapped around proteins called histones chromosomes • A human cell has 46 chromosomes; i.e. 46 segments of DNA wrapped around proteins • These chromosomes come in homologous pairs – one from mom and one from dad Fig. 16-21a Nucleosome (10 nm in diameter) DNA double helix (2 nm in diameter) H1 Histones DNA, the double helix Histones Histone tail Nucleosomes, or “beads on a string” (10-nm fiber) Fig. 16-21b Chromatid (700 nm) 30-nm fiber Loops Scaffold 300-nm fiber Replicated chromosome (1,400 nm) 30-nm fiber Looped domains (300-nm fiber) Metaphase chromosome Sex Determination Is Directed By Our Genome • Humans have 23 pairs of chromosomes – 22 pairs of autosomes – X and Y = 1 pair of sex chromosomes Figure 26-1 Prokaryotes vs Eukaryotes • No nucleus vs True nucleus • Many similarities – Common biological macromolecules – Common genetic code – Common metabolic pathways – Common physical/cell structure • Many differences – Size – Cellular complexity – Metabolic diversity Prokaryotic and Eukaryotic Cells: An Overview • Prokaryotes – Lack nucleus – Lack various internal structures bound with phospholipid membranes – Are small (~1.0 µm in diameter) – Have a simple structure – Include bacteria and archaea © 2012 Pearson Education Inc. Figure 3.2 Typical prokaryotic cell Inclusions Ribosome Cytoplasm Flagellum Nucleoid Glycocalyx Cell wall Cytoplasmic membrane Prokaryotic and Eukaryotic Cells: An Overview • Eukaryotes – – – – – © 2012 Pearson Education Inc. Have nucleus Have internal membrane-bound organelles Are larger (10–100 µm in diameter) Have more complex structure Include algae, protozoa, fungi, animals, and plants Figure 3.3 Typical eukaryotic cell Nuclear envelope Nuclear pore Nucleolus Lysosome Mitochondrion Centriole Secretory vesicle Golgi body Cilium Transport vesicles Ribosomes Rough endoplasmic reticulum Smooth endoplasmic reticulum Cytoplasmic membrane Cytoskeleton Cells • A cell is the functional unit of biology • All living things are made up of cells • A cell must contain the information and ability necessary to maintain itself and reproduce itself • Therefore, all cells must contain 4 basic components – Chromosomes: genetic information for the cell – Cell/plasma membrane: semi-permeable boundary – Ribosomes: protein factory of the cell – Cytosol/cytoplasm: the internal liquid portion of the cell Eukaryotic cells • Human cells are eukaryotic • Eukaryotes are defined by having a nucleus (and other internal membrane-bound organelles) • These organelles allow for compartmentalization of individual functions for the cell Nucleus • The defining feature of a eukaryotic cell • It is a double-membraned organelle with the primary role of storing and protecting DNA • In order to fit inside the nucleus (or cell in general), the DNA gets wrapped around proteins chromosome • Within the nucleus is the nucleolus, the site of ribosome production • To move RNA and ribosomes out of the nucleus, it must contain nuclear pores, through which movement is regulated Fig. 6-10 Nucleus 1 µm Nucleolus Chromatin Nuclear envelope: Inner membrane Outer membrane Nuclear pore Pore complex Surface of nuclear envelope Rough ER Ribosome 1 µm 0.25 µm Close-up of nuclear envelope Pore complexes (TEM) Nuclear lamina (TEM) Ribosomes • Ribosomes are “protein factories” • They translate RNA into proteins in the cell cytoplasm • Ribosomes are found in two locations, freefloating in th cytoplasm or bound to the rough ER • Free-floating ribosomes tend to make proteins that will function within the cytoplasm or nucleus • Bound ribosomes tend to make proteins that Fig. 6-11 Cytosol Endoplasmic reticulum (ER) Free ribosomes Bound ribosomes Large subunit 0.5 µm TEM showing ER and ribosomes Small subunit Diagram of a ribosome Endoplasmic reticulum (ER) • Organelle contiguous with the outer nuclear membrane, whose job is typically production • Two types: rough and smooth • Rough ER: looks “rough” because of the presence of ribosomes on the surface; makes proteins • Smooth ER: typically involved in lipid synthesis and sugar storage/modification Fig. 6-12 Smooth ER Rough ER ER lumen Cisternae Ribosomes Transport vesicle Smooth ER Nuclear envelope Transitional ER Rough ER 200 nm Golgi apparatus (body) • The storage and transport center of the cell (FedEx) • Products from the ER get delivered to the Golgi, which packages them, modifies them as needed, and directs them to the correct location within or out of the cell • Also, products brought into the cell often get directed to the Golgi for proper sorting • Consists of stacked membrane sacks • Products get delivered by small transport Fig. 6-13 cis face (“receiving” side of Golgi apparatus) 0.1 µm Cisternae trans face (“shipping” side of Golgi apparatus) TEM of Golgi apparatus Lysosome/Peroxisome • Two organelles involved in breakdown • As cellular portions get “old and worn-down,” or as external products are engulfed and must get broken down, they are sent to these organelles • Peroxisome – Oxidative breakdown – Uses toxic oxygen species like peroxide & superoxides • Lysosome (not found in plants) – Enzymatic breakdown – Uses degradative enzymes to digest macromolecules Fig. 6-14 Nucleus 1 µm Vesicle containing two damaged organelles 1 µm Mitochondrion fragment Peroxisome fragment Lysosome Lysosome Digestive enzymes Plasma membrane Lysosome Peroxisome Digestion Food vacuole Vesicle (a) Phagocytosis (b) Autophagy Mitochondrion Digestion Vacuoles • Many cells need to store components • For storage, vesicles will congregate into one organelle called a storage vacuole • Different types of cells have individual vacuoles to store various different molecules • Plant cells often contain a large Central Vacuole, which stores primarily water and provides rigidity to the cell Fig. 6-15 Central vacuole Cytosol Nucleus Central vacuole Cell wall Chloroplast 5 µm Fig. 6-16-3 Nucleus Rough ER Smooth ER cis Golgi trans Golgi Plasma membrane Mitochondria • Powerhouse of the cell • Site of Cellular Respiration, where ATP is made • ATP: adenosine triphosphate – Adenine + ribose + 3 phosphates – cellular battery used to charge chemical reactions • All cellular ATP is charged in the mitochondria, then gets delivered to other parts of the cell where it is broken down into ADP • Breaking the terminal phosphate bond releases energy, which can be used to power other Fig. 6-17 Intermembrane space Outer membrane Free ribosomes in the mitochondrial matrix Inner membrane Cristae Matrix 0.1 µm Fig. 9-UN3 becomes oxidized becomes reduced Fig. 8-12 ATP + H2O Energy from catabolism (exergonic, energy-releasing processes) ADP + P i Energy for cellular work (endergonic, energy-consuming processes) Fig. 9-6-3 Electrons carried via NADH and FADH2 Electrons carried via NADH Citric acid cycle Glycolysis Pyruvate Glucose Oxidative phosphorylation: electron transport and chemiosmosis Mitochondrion Cytosol ATP ATP ATP Substrate-level phosphorylation Substrate-level phosphorylation Oxidative phosphorylation Chloroplast • Found only in plant cells • Site of photosynthesis • Photosynthesis: Using light energy to synthesize glucose from CO2 in the air Fig. 6-18 Ribosomes Stroma Inner and outer membranes Granum Thylakoid 1 µm Cytoskeleton • Cells are not just free-floating bags of organelles, but instead are full of internal structure • This internal structure comes from their cytoskeleton • There are 3 main classes of cytoskeletal molecules – Microfilaments: smallest type, made of actin – Intermediate filaments: diverse array of proteins – Microtubules: largest type, made of tubulin • The cytoskeleton provides internal structure, Table 6-1 10 µm 10 µm 10 µm Column of tubulin dimers Keratin proteins Actin subunit Fibrous subunit (keratins coiled together) 25 nm 7 nm Tubulin dimer 8–12 nm Fig. 6-23 Direction of swimming (a) Motion of flagella 5 µm Direction of organism’s movement Power stroke Recovery stroke (b) Motion of cilia 15 µm Cellular connections • For multicellular organisms, cells must be able to communicate outside individual cells to work together • Many cells are connected to each other, creating layers of tissues and organs • These cells are often connected to an extracellular matrix (ECM) or basement membrane • Many cells are interconnected through communication sites called tight/gap junctions (primarily in animals) or desmosomes Fig. 6-32 Tight junction Tight junctions prevent fluid from moving across a layer of cells 0.5 µm Tight junction Intermediate filaments Desmosome Desmosome Gap junctions Space between cells Plasma membranes of adjacent cells Extracellular matrix 1 µm Gap junction 0.1 µm