Lecture 1_Introduction to Cells_GP compressed(1) (3).pptx

Cell Form and Function Lecture 1: Macromolecular Structures: Proteins, Lipids and Membranes Parts of Chapters 2, 3 and 7 Learning Outcomes Describe the importance of macromolecule assembly and polymerisation for cell function Describe and und...

Cell Form and Function Lecture 1: Macromolecular Structures: Proteins, Lipids and Membranes Parts of Chapters 2, 3 and 7 Learning Outcomes Describe the importance of macromolecule assembly and polymerisation for cell function Describe and understand the cellular functions of key macromolecules in the cell  Composition of cells Important Macromolecules Nucleic acid Proteins Carbohydrat es Macromolecules are often synthesized by stepwise polymerization of monomers Proteins must fold, forming their ‘native’ conformati on, to be functional. Many Proteins Spontaneously Fold into Their Biologically Functional State The immediate product of amino acid polymerization is a polypeptide Once the polypeptide has assumed its correct three- dimensional structure, or conformation, it is called a protein The native (natural) conformation of a protein can be altered by changing conditions Denaturation and Renaturation The unfolding of polypeptides, denaturation, leads to loss of biological activity (function) When denatured proteins are returned to conditions in which the native conformation is stable, they may undergo renaturation, a refolding into the correct conformation In some cases, renaturation is associated with the return of the protein function  Beyond non-covalent interactions. In addition to non-covalent interactions, covalent bonds are sometimes needed for a protein to adopt its proper shape, or conformation Covalent disulfide bonds form between the sulfur atoms of two cysteine residues They form by oxidising the cysteines and can be broken only by reduction. Once formed, disulfide bonds confer considerable stability to the protein conformation  Polypeptide Folding Is Facilitated by Molecular Chaperones Proteins must fold into their correct three- dimensional shapes before they can function Protein folding is usually facilitated by proteins called molecular chaperones; often several are required, acting in sequence Chaperones bind polypeptide chains during the early stages of folding Molecular chaperones are not components of Pearson Education, Ltd. © 2017 Misfolding and Molecular Chaperones If folding goes awry, chaperones can sometimes rescue the proteins and fold them properly Alternatively, improperly folded proteins may be destroyed Some kinds of incorrectly folded proteins bind to each other and form insoluble aggregates within and between cells  Molecular Chaperones Stress conditions can cause protein misfolding. Cells respond by trying to assist refolding of proteins - chaperones. Two of the most widely occurring chaperone families are Hsp70 and Hsp60 (Hsp = heat- shock protein) © 2017 Pearson Education, Ltd.  Higher Levels of Assembly A higher level of assembly is possible in the case of proteins that are organized into multiprotein complexes Can have different proteins in the complex, or the same protein, e.g. haemoglobin https://www.medschoolcoach.com/electron-transport-chain-mcat-bioche Self-Assembly Also Occurs in Other Cellular Structures The same principles of self-assembly that apply to polypeptides also apply to the assembly of more complex structure Membranes are not polymers, but occur due to self-assembly of phospholipids, cholesterol, proteins etc. However, they are regarded as macromolecules because of their high molecular weight and their importance in cellular structures, particularly membranes © 2017 Pearson Education, Ltd.  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 However, some are amphipathic, having polar and nonpolar regions Functions include energy storage, membrane structure, or specific biological functions such as signal transmission © 2017 Pearson Education, Ltd.  The Main Classes of Lipids The lipids can be divided into six classes based on their structure Fatty acids Glycolipi ds Triacylglycerols Steroids Phospholipids Terpines © 2017 Pearson Education, Ltd.  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 Usually 10-20 carbons Usually even number (2C additions) Highly reduced – oxidation releases energy https://microbenotes.com/fatty-acids/ Phospholipid synthesis The fundamentals  Phospholipids Phospholipids are important to membrane structure because of their amphipathic nature Phospholipids can be divided into phosphoglycerides or sphingolipids, depending on their chemistry © 2017 Pearson Education, Ltd.  Phosphoglyceri des Phosphoglycerides are the predominant phospholipids in most membranes The basic components of phosphoglycerides is phosphatidic acid, which has two fatty acids and a phosphate group attached to a glycerol  Phosphoglyceri des The polar group is usually serine, ethanolamine, choline, or inositol Typical phosphoglycerides often have one saturated and one unsaturated fatty acid The length and degree of saturation of the fatty acids have profound effects on membrane fluidity Sphingolipids Sphingolipids are based on the amine sphingosine, which has a long hydrocarbon chain with a single site of unsaturation near the polar end © 2017 Pearson Education, Ltd. Sphingolipids Sphingolipids are predominantly found in the outer leaflet of the plasma membrane bilayer, often in lipid rafts, localized domains within a membrane A whole family of sphingolipids exists, with different polar groups attached. Spingomyelin © 2017 Pearson Education, Ltd. Glycosphingolipids Glycosphingolipids - Tay- Sachs Disease Glycolipids Are Specialized Membrane Components Glycolipids are lipids containing a carbohydrate Carbohydrate groups attached to a glycolipid may be one to six sugar units (D-glucose, D- galactose, or N-acetyl-D-galactosamine) Glycolipids occur largely on the outer monolayer of the plasma membrane https://en.wikipedia.org/wiki/Glycolipid Sterols Orientation of cholesterol in lipid bilayer Fatty Acids Are Essential to Membrane Structure and Function Unique lipid compositionCardiolipin of organelle membranes Membrane Asymmetry  Extracellula M em br an Cytosol e Membrane Asymmetry Tends to Be Maintained Lipids move freely and randomly (mostly) within their monolayer Transverse Diffusion maintains asymmetry Other factors influencing membrane fluidity Membrane-membrane barriers Poorly mobile clusters - Lipid Rafts Functions of Lipid Rafts Membrane Proteins Membrane Proteins Are Oriented Asymmetrically Across the Lipid Bilayer Many Membrane Proteins Are Glycosylated Roles of Glycoproteins Glycocalyx Lipid Trafficking and Storage