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Lipids and Proteins I. Lipids A. Fats 1. fatty acids a. saturated b. unsaturated 2. trans fats B. Phosopholipids C. Steroids 1. LDL 2. HDL Lipids Lipids are a diverse group of hydrophobic molecules Lipids – Are the one class of large biological molecules that do not consist of polymers – Share the common trait of being hydrophobic Fats – Are constructed from two types of smaller molecules, a single glycerol and usually three fatty acids – Vary in the length and number and locations of double bonds they contain Fats • Vary in the length and number and locations of double bonds they contain Saturated fatty acids – Have the maximum number of hydrogen atoms possible – Have no double bonds Stearic acid (a) Saturated fat and fatty acid Figure 5.12 Unsaturated fatty acids – Have one or more double bonds – Mono-unsaturated or polyunsaturated Oleic acid Figure 5.12 (b) Unsaturated fat and fatty acid cis double bond causes bending Monoacylglycerol Diacyglycerol Triacylglycerol Ester linkage In unsaturated fatty acids, there are two ways the pieces of the hydrocarbon tail can be arranged around a C=C double bond. In cis bonds, the two pieces of the carbon chain on either side of the double bond are either both “up” or both “down,” such that both are on the same side of the molecule. In trans bonds, the two pieces of the molecule are on opposite sides of the double bond, that is, one “up” and one “down” across from each other Naturally-occurring unsaturated vegetable oils have almost all cis bonds, but using oil for frying causes some of the cis bonds to convert to trans bonds. If oil is used only once like when you fry an egg, only a few of the bonds do this so it’s not too bad. However, if oil is constantly reused, like in fast food French fry machines, more and more of the cis bonds are changed to trans until significant numbers of fatty acids with trans bonds build up. The reason this is of concern is that fatty acids with trans bonds are carcinogenic, or cancer-causing. The levels of trans fatty acids in highly-processed, lipid-containing products such as margarine are quite high, and the government is considering requiring that the amounts of trans fatty acids in such products be listed on the labels. Phospholipids – Have only two fatty acids – Have a phosphate group instead of a third fatty acid Phospholipid structure – Consists of a hydrophilic “head” and hydrophobic “tails” CH2 CH2 O O P O– + N(CH3)3 Choline Phosphate O CH2 CH O O C O C CH2 Glycerol O Fatty acids Hydrophilic head Hydrophobic tails Figure 5.13 (a) Structural formula (b) Space-filling model (c) Phospholipid symbol The structure of phospholipids – Results in a bilayer arrangement found in cell membranes WATER Hydrophilic head WATER Hydrophobic tail Figure 5.14 Steroids Steroids – Are lipids characterized by a carbon skeleton consisting of four fused rings H 3C CH3 CH3 Figure 5.15 HO CH3 CH3 One steroid, cholesterol – Is found in cell membranes – Cholesterol is the precursor to our sex hormones and Vitamin D. Vitamin D is formed by the action of UV light in sunlight on cholesterol molecules that have “risen” to near the surface of the skin. – Our bodies make about 2 g of cholesterol per day, and that makes up about 85% of blood cholesterol, while only about 15% comes from dietary sources. Lipoproteins are clusters of proteins and lipids all tangled up together. These act as a means of carrying lipids, including cholesterol, around in our blood. Two main categories of lipoproteins distinguished by how compact/dense they are. 1. LDL or low density lipoprotein is the “bad guy,” being associated with deposition of “cholesterol” on the walls of someone’s arteries. 2. HDL or high density lipoprotein is the “good guy,” being associated with carrying “cholesterol” out of the blood system, and is more dense/more compact than LDL. FYI only!!! An emulsifying agent is a substance which is soluble in both oil and water, thus enabling the two to mix. A “famous” phospholipid is lecithin which is found in egg yolk and soybeans. Egg yolk is mostly water but has a lot of lipids, especially cholesterol, which are needed by the developing chick. Lecithin is used to emulsify the lipids and hold them in the water as an emulsion. Lecithin is the basis of the classic emulsion known as mayonnaise Proteins Proteins have many structures, resulting in a wide range of functions Proteins do most of the work in cells and act as enzymes Proteins are made of monomers called amino acids 5.1 An overview of protein functions Enzymes – Are a type of protein that acts as a catalyst, speeding up chemical reactions Active site is available for a molecule of substrate, the reactant on which the enzyme acts. 2 1 Substrate binds to enzyme. Substrate (sucrose) Enzyme (sucrase) Glucose OH H O Fructose Figure 5.16 H 2O 3 Substrate is converted to products. 4 Products are released. Amino acids – Are organic molecules possessing both carboxyl and amino groups – Differ in their properties due to differing side chains, called R groups Twenty Amino Acids 20 different amino acids make up proteins CH3 CH3 H H3N+ C CH3 O H3N+ C H Glycine (Gly) O– C H3N C H + O– C CH2 CH2 O H 3N C H Valine (Val) Alanine (Ala) CH CH3 CH3 O CH3 CH3 C + O– O C H Leucine (Leu) H3C H3N + O– CH C O C H Isoleucine (Ile) O– Nonpolar CH3 CH2 S NH CH2 CH2 H3N+ C H H3N+ C O– Methionine (Met) Figure 5.17 CH2 O C H CH2 O C O– Phenylalanine (Phe) H3N+ C H O C H2C CH2 H2 N C O C H O– Tryptophan (Trp) Proline (Pro) O– OH OH Polar H3N + CH2 C O C H CH H3N O– Serine (Ser) C + O C H3N O– H + CH2 C H O C CH2 H3N O– C + O C H Electrically charged H3N + C + O– O– O NH3+ NH2 C CH2 C CH2 CH2 CH2 CH2 CH2 CH2 O H O– H3N + CH2 C O C H O– H3N + CH2 C H Aspartic acid (Asp) O– + CH2 C O C H O– Glutamine (Gln) Asparagine (Asn) C C C H3N Basic O C CH2 O H Acidic –O CH2 H3N Tyrosine (Tyr) Cysteine (Cys) Threonine (Thr) C NH2 O C SH CH3 OH NH2 O Glutamic acid (Glu) O– Lysine (Lys) NH2+ H3N + CH2 O C NH+ H3N + CH2 C H NH CH2 O C C O– H O C O– Arginine (Arg) Histidine (His) Amino Acid Polymers Amino acids – Are linked by peptide bonds Polypeptides Polypeptides – Are polymers (chains) of amino acids A protein – Consists of one or more polypeptides Protein Conformation and Function A protein’s specific conformation (shape) determines how it functions Four Levels of Protein Structure Primary structure +H – Is the unique sequence of amino acids in a polypeptide 3N Amino end Amino acid subunits Gly ProThrGly Thr Gly Glu Cys LysSeu LeuPro Met Val Lys Val Leu Asp AlaVal ArgGly Ser Pro Ala Glu Lle Leu Ala Gly Asp Thr Lys Ser Lys TrpTyr lle Ser Pro Phe His Glu AlaThrPhe Val Asn His Ala Glu Val Thr Asp Tyr Arg Ser Arg Gly Pro lle Ala Ala Leu Leu Ser Pro SerTyr Tyr Ser Thr Thr Ala Val Val Glu Thr Pro Lys Asn Figure 5.20 c o o– Carboxyl end Secondary structure – Is the folding or coiling of the polypeptide into a repeating configuration – Includes the helix and the pleated sheet pleated sheet Amino acid subunits O H H C C N C N H R R O C C R N H C H R O C O C N H N H N H O C O C H H C R H C R H C R C R N H O C N H O C O C H C O N H N C C H R H R Figure 5.20 C R O H H C C N C C N O H H R R O H H C C N C C N OH H R O O C H H C H N HC N H C N H C N C H H C O C O R R H helix R R O H H C C N C C N OH H R O C H H NH C N C H O C R R C C O R H C N HC N H O C Tertiary structure – Is the overall three-dimensional shape of a polypeptide – Results from interactions between amino acids and R groups Hydrogen bond CH22 CH O H O H 3C CH CH3 H 3C CH3 CH Hydrophobic interactions and van der Waals interactions Polypeptide backbone HO C CH2 CH2 S S CH2 Disulfide bridge O CH2 NH3+-O C CH2 Ionic bond Quaternary structure – Is the overall protein structure that results from the aggregation of two or more polypeptide subunits Polypeptide chain Collagen Chains Iron Heme Chains Hemoglobin Review of Protein Structure +H 3N Amino end Amino acid subunits helix Sickle-Cell Disease: A Simple Change in Primary Structure Sickle-cell disease – Results from a single amino acid substitution in the protein hemoglobin Primary structure Normal hemoglobin Val His Leu Thr Pro Glul Glu 1 2 3 4 5 6 7 Secondary and tertiary structures Red blood cell shape Figure 5.21 Val His Leu Thr Pro Molecules do not associate with one another, each carries oxygen. Normal cells are full of individual hemoglobin molecules, each carrying oxygen Val Glu structure 1 2 3 4 5 6 7 Secondary subunit and tertiary structures Quaternary Hemoglobin A structure Function Sickle-cell hemoglobin . . . Primary Quaternary structure Function 10 m ... Exposed hydrophobic region subunit 10 m Hemoglobin S Molecules interact with one another to crystallize into a fiber, capacity to carry oxygen is greatly reduced. Red blood cell shape Fibers of abnormal hemoglobin deform cell into sickle shape. What Determines Protein Conformation? Protein conformation Depends on the physical and chemical conditions of the protein’s environment Temperature, pH, etc. affect protein structure •Denaturation is when a protein unravels and loses its native conformation (shape) Denaturation Normal protein Figure 5.22 Denatured protein Renaturation The Protein-Folding Problem Most proteins – Probably go through several intermediate states on their way to a stable conformation – Denaturated proteins no longer work in their unfolded condition – Proteins may be denaturated by extreme changes in pH, temperature, salinity or heavy metals Chaperonins – Are protein molecules that assist in the proper folding of other proteins Cap Polypeptide Correctly folded protein Hollow cylinder Steps of Chaperonin Chaperonin (fully assembled) Action: An unfolded poly1 peptide enters the cylinder from one Figure 5.23 end. The cap attaches, causing The cap comes 3 the cylinder to change shape off, and the in properly such a way that it creates a folded protein is hydrophilic environment for released. the folding of the polypeptide. 2 Prions Prions are slow-acting, virtually indestructible infectious proteins that cause brain diseases in mammals Prions propagate by converting normal proteins into the prion version Scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob disease in humans are all caused by prions What happens if a protein isn’t folded correctly? Prions are formed – misfolded versions of normal proteins X-ray crystallography – Is used to determine a protein’s threedimensional structure X-ray Photographic film Diffracted X- rays X-ray source diffraction pattern X-ray beam Crystal Nucleic acid Protein Figure 5.24 (b) 3D computer model (a) X-ray diffraction pattern Nucleic Acids Nucleic acids store and transmit hereditary information Genes – Are the units of inheritance – Program the amino acid sequence of polypeptides – Are made of nucleotide sequences on DNA The Roles of Nucleic Acids There are two types of nucleic acids – Deoxyribonucleic acid (DNA) – Ribonucleic acid (RNA) Deoxyribonucleic Acid DNA – Stores information for the synthesis of specific proteins – Found in the nucleus of cells DNA Functions – Directs RNA synthesis (transcription) – Directs protein synthesis through RNA DNA (translation) 1 Synthesis of mRNA in the nucleus NUCLEUS 2 Movement of mRNA into cytoplasm via nuclear pore mRNA CYTOPLASM mRNA Ribosome 3 Synthesis of protein Figure 5.25 Polypeptide Amino acids The Structure of Nucleic Acids 5’ end Nucleic acids – Exist as polymers called polynucleotides 5’C O 3’C O O 5’C O 3’C (a) Polynucleotide, or nucleic acid Figure 5.26 OH 3’ end Each polynucleotide – Consists of monomers called nucleotides – Sugar + phosphate + nitrogen base Nucleoside Nitrogenous base O O P 5’C O CH2 O O Phosphate group Figure 5.26 (b) Nucleotide 3’C Pentose sugar Nucleotide Monomers Nucleotide monomers Nitrogenous bases Pyrimidines NH2 O O C C CH C 3 N CH C CH HN HN CH C CH C C CH N N O N O O H H H Cytosine Thymine (in DNA)Uracil (in RNA) RNA) Uracil (in U C U T – Are made up of nucleosides (sugar + base) and phosphate groups Purines O NH2 N C C N C C NH N HC HC C CH N C N NH2 N N H H Adenine Guanine A G 5” Pentose sugars HOCH2 O 4’ OH H H 1’ 5” HOCH2 O OH 4’ H H 1’ H H H 3’ 2’ H 3’ 2’ OH H OH OH Deoxyribose (in DNA) Ribose (in RNA) Figure 5.26 (c) Nucleoside components Nucleotide Polymers Nucleotide polymers – Are made up of nucleotides linked by the–OH group on the 3´ carbon of one nucleotide and the phosphate on the 5´ carbon on the next Gene The sequence of bases along a nucleotide polymer – Is unique for each gene The DNA Double Helix Cellular DNA molecules – Have two polynucleotides that spiral around an imaginary axis – Form a double helix The DNA double helix – Consists of two antiparallel nucleotide strands 5’ end 3’ end Sugar-phosphate backbone Base pair (joined by hydrogen bonding) Old strands A 3’ end Nucleotide about to be added to a new strand 5’ end 3’ end Figure 5.27 5’ end New strands 3’ end A,T,C,G The nitrogenous bases in DNA – Form hydrogen bonds in a complementary fashion (A with T only, and C with G only) DNA and Proteins as Tape Measures of Evolution Molecular comparisons – Help biologists sort out the evolutionary connections among species The Theme of Emergent Properties in the Chemistry of Life: A Review Higher levels of organization – Result in the emergence of new properties Organization – Is the key to the chemistry of life