Life, The Science of Biology

• Tenth Edition published 2014. Abbreviated as Sadava.
• Authors: David Sadava, David M. Hillis, H. Craig Heller, and May R. Berenbaum
• See notes on Sadava Chapter 2 reviewing general chemistry on this page

Chapter 3: Macromolecules I - Proteins, Carbohydrates, Lipids (p. 39-61)

• Four kinds of macromolecules: proteins, carbohydrates, lipids, and nucleic acids
• Macromolecular polymers are made of different types of monomers:
  • Proteins are made up of amino acid monomers.
  • Carbohydrates are made up of simple sugar monomers.
  • Lipids are made up of lipid monomers connected by noncovalent bonds
• In general, only polymers with molecular weights > 1000 are considered macromolecules.
• Figure 3.1 (p. 40) has a good diagram of various functional groups, categories of compounds, and example compounds.
• Figure 3.3 (p. 41) has good % breakdown of macromolecules in living tissue.
• Reactants Monomer₁ + … + Monomer_n –> Polymer via removal of H₂0 and addition of energy (endothermic reaction). Also called condensation or dehydration reaction.
• Reverse reaction of Reactant Polymer —> breaking into smaller monomers by adding water and releasing energy from the reactant (exothermic reaction). Called hydrolysis.

Proteins

• The protein alphabet of monomers cosists of 20 amino acids. All proteins consist of a permutation of these 20 elemental units.
  • The smaller limit of proteins is around 51 amino acids for insulin with molecular weight of 5,733.
  • The upper limit of protein chain size is around 27,000 amino acid for the muscle protein titin with a molecular weight of almost 3 million.
• Polypeptide chains are linear (aka unbranched) sequences of covalently linked amino acids.
• Amino acids have 3 functional groups plus 1 hydrogen surrounding the central α-carbon:
  1. carboxyl functional group -COOH ionizes to -COO^-
  2. amine group -NH₂ ionizes to -NH₃⁺
  3. R side chain
• Amino acids can appear as optical isomers with D- for righthand and L- for lefthand configurations. (d-amino acids for the Latin dextro; l-amino acids for the Latin levo). Only L- configurations appear in nature / are used by living cells with the rare exception of some structural proteins used in bacterial cell walls.
• See Table 3.2 on p. 44 for good categorization of 20 amino acids based on R side chains.
• Amino acids are combined using a condensation / dehydration reaction that forms a peptide linkage. The N- terminus all the way on the left of the protein is by considered the “beginning” of the sentence and the C- terminus all the way at the right end is considered the “end” of the protein “sentence”.
• Primary structure is the sequence of repeating -N-C-C-N-C-C-
• Good diagram of primary, secondary, tertiary, and quartenary structure on p. 46.
• Each monomer is an amino acid. A short sequence of amino acids is called a peptide. Multiple peptides together form polypeptides and protein subunits.
• Concept of molecular chaperones which help guide proper folding of proteins directly after peptide synthesis or after denaturation to refold. Cancer cells produce chaperones to help secure proper folding for cancer-promoting proteins (p. 51). See p. 51 also for example of HSP60 cage + lid.

Secondary structure of proteins

• α-helices are right-handed and the R-groups extend outward from the central axis of the -N-C-C-N-C-C- chain in a steady spiral. Coiling results from the hydrogen bonding between the small δ⁺ of the H⁺ on the N and the δ^- on the carbonyl oxygen C=O of another amino acid in the chain.
• Pleated β-sheets

Tertiary structure of proteins

• Definitive 3D structure of a protein, which usually includes a polar (hydrophilic) exterior region and nonpolar (hydrophobic) interior where reactions happen.
• α-helices and β pleatedsheets secondary structures are determined by hydrogen bonds. Meanwhile, tertiary structure is caused by nonovalent interactions between the various -R side chains functional groups hanging off the central polypeptide -N-C-C-N-C-C- . Examples:
  • Covalent disulfide bridges
  • Hydrogen bonds between side chains
  • Hydrophobic side chains an aggregate together in the interior of the protein. These close interactions are stabilized by van der Waals forces.
  • Ionic bonds can form salt bridges between positively and negatively charged side chains.
• p. 48 interesting example of how Christian Anfinsen used ribonuclease A to prove that primary structure contains all the info needed to determine tertiary structure.

Quartenary structure

• When a protein consists of two or more polypeptides, called subunits, each of these subunits fold into their own tertiary structure.
• The interaction of these subunits is the quartenary structure.

Proteins and associated functions - p.42

Category	Function
Enzymes	Catalyze biochemical reactions
Structural proteins	Provide physical stability and movement
Defensive proteins	Recognize and react to nonself substances (e.g. antibodies)
Signaling proteins	Control physiological processes (e.g. hormones)
Receptor proteins	Receive and respond to chemical signals
Membrane transporters	Regulate passage of substances across cell membranes
Storage proteins	Store amino acids for later use
Transport proteins	Bind and carry substances within the organism
Gene regulatory proteins	Determine rate of expression of genes

Carbohydrates - p. 51

• Usually have the generic formula C_mH_2nO_n where m,n ∈ {positive integers}.
• Carbohydrates have important roles in energy storage/transport and structure like cellulose in plants.
• Chemically modified carbohydrates also play critical structural roles in biology:
  • galactosamine is a major part of cartilage (p. 55)
  • a derivative of glucosamine is a component of chitin which is important in arthropods and fungi.
• Four categories of carbohydrates based on number of monomers:
  1. Monosaccharides like glucose
  2. Disaccharides like sucrose, a combination of glucose and fructose
  3. Oligosaccharides are made up of about 3-20 monosaccharides
  4. Polysaccharides are made up of hundreds or thousands of monosaccharides. Examples: starch, glycogen, cellulose.

Monosaccharides

• In living systems, most monosaccharides are the dextro- / D- / (right-handed) optical isomer.
• Pentoses are five-carbon sugars, including ribose which is part of the sugar-phosphate backbone of RNA and deoxyribose which forms the sugar-phosphate backbane of DNA.
• Hexoses are 6-carbon sugars such as glucose, fructose, mannose, and galactose.
  • Glucose are 6-carbon sugars that can take the form of straight carbon chains or rings in chair configuration. The ring consists of 5 carbons and an oxygen; the 6th carbon hangs off of the ring at the 5-carbon.
  • Glucose comes in both α- and β-isomers which convert to each other readily in aqeous solution and are in equilibrium.
• Dehydration synthesis reactions connects monosaccharides into disaccharides, oligosaccharides, and polysaccharides via glycosidic linkages

Polysaccharides

• Whereas all proteins are linear chains of amino acids, monosaccharides can bond in many branching ways to form polysaccharides.
• Starches are polysaccharides which are often branched made up of glucose monomers via with α-glycosidic linkages.
  • These branches attach from the via 1-α carbon of glucose monomer A to either the 4 or 6 carbon on the glucose molecule B.
  • Starch is the primary energy storage for plants. Some plant starches are unbranched like amylose which can consist of 300-3000 (or even more) monomeric glucoses.
• Glycogen is highly branched and used in animals.
  • Similarly to starch for plants, glycogen acts as an energy store for animals in the liver and in the muscles.
  • The branches occur every 10-14 glucose monomers between the carbon 6 of the main branch and the 1-α carbon of the branched glucose. See this Wiki link on the brancher enzyme for more.
  • Unlike glucose which is readily soluble in water, glycogen is nonpolar and thus does not dissolve in water which relieve osmotic pressure in animal cells allowing more compact storage.
• Cellulose is a critical componet of plant cell walls. Connected via glycosidic linkages at the 1-β carbon (instead of the 1-α carbon seen in starch and glycogen). This makes it much harder to break down cellulose.
• Chemically modified carbs which have undergone redox reactions and/or had functional groups like phosphate, amino, or N-acteyl gropus added. Cartilage and chitin.
• Also refer to carbohydrate panels in Alberts 5th, p. 112-113.

Lipids and phospholipids - p. 56

• Types of lipids
  • Fats and oils (triglycerides) store energy.
  • Phosopholipids provide structure to membranes.
  • Carotenoids and chlorophylls capture light energy for plants.
  • Steroids and modified fatty acids play regulatory roles as hormones as vitamins.
  • Fat in animals provides thermal insulation
  • Myelin (fatty sheath) surrounding neuronal axons provide electrical insulation to speed the action potential.
  • Oil and wax on the surface of skin and leaves helps repel water and prevents excess evaporation.
• Simple lipids like fats and oils consist of triglycerides.
  • A triglyceride typically combines an alcohol (like glyceryl with 3 -OH hydroxyl groups) with three fatty acids which are simply long chains of hydrocarbons.
  • The glycerol and fatty acids are bonded by 3 dehydration/condensation synthesis reactions that yield 3 water molecules.
  • The resulting bonds are ester linkages with a central oxygen between each fatty acid and the glycerol molecule.
  • Saturated fatty acid = full of hydrogen atoms, no double bonding
  • Unsaturated fatty acid = some missing hydrogen atoms aka some double or triple bonding somewhere.
• Phospholipids are amphipathic; have a polar phosphate end and a nonpolar hydrocarbon chain end.
• Carotenoids are a family of light-absorbing pigments found in plants and animals. β-carotene aka betacarotene is part of the photosynthesis process for plants. Meanwhile, betacarotine breaks down to two vitamin A molecules for humans as part of the visual system.
• Steroids are multiply linked rings of hydrocarbons that are important as membrane components as well as signals in the hormone system.
• Vitamins A, D, E, and K are lipids, aka they are fat soluble.
• Waxes are hydrophobic and at room temperature, malleable/plastic. Each wax molecule sonists of a saturated long-chain fatty acid connected via an ester linkage to a long-chain alochol. As such, they have between 40-60 CH₂ groups.
• Lipid panels in Alberts 5th Ed, p. 114-115
  • Stearic acid (C18) and palmitic acid (c16) are saturated aka full of hydrogens and only carbon single bonds.
  • Oleic acid (C18) is unsaturated with a single double bond between C9 and C10.
  • Glycerol is a 3-carbon alcohol with an -OH hydroxyl attached to C1, C2, and C3 respectively. It serves as the backbone for triglycerides when 3 fatty acids attach via dehydration/condensation synthesis at the ester linkage.
  • Carboxyl groups -COOH give rise to: (a) ionized form -COO^-, (b) esters, (c) amides.
  • Phospholipids where one of the 3 fatty acids attached to the glycerol backbone is replaced by a hydrophilic phosphate group -PO₄^3- . Thus forming a hydrophilic head and 2 hydrophobic tails.
  • The phosophate group can also attach to other moeities, such as choline in the example of phosphatidylcholine.
  • Isoprene units like 2-methyl-1,3 butadiene. See also the Organic Chemistry section.

Chapter 4: Macromolecules II - Nucleic Acids (p. 62-76)

• See notes on Alberts 5th edition

Chapter 12: Inheritance, Genes, Chromosomes (p. 232 - 258)

• p. 234 - Character is a phenotypic attribute and a trait is a particular value for that attribute.
• A gene can have more than 2 alleles in the population. Example of the C gene in rabbits that determines rabbit coat color (p. 242):
  • The dominant wild-type C allele produces a dark gray coat
  • c^chd recessive allele produces a Chinchilla coat
  • c^h recessive allele produces a Himalayan coat aka point coloration where color is restricted to ears, feet, and other tips.
  • c recessive allele produces an albino rabbit with white fur.

Chapter 16: Regulation of Gene Expression

• 9/11/2020

Introduction

• Example of how the enzyme β-Galactosidase metabolizes 2-ring sugars like lactose by breaking the glycosidic bond into monosaccharides. (p. 329)
• Three proteins are involved in the absorption and metabolism of lactose by E. coli:
  1. β-Galactoside permease is a carrier protein in the bacterial plasma membrane that moves lactose into the cell. Coded by the lacY gene.
  2. β-Galactosidase hydrolyzes lactose into the monosaccharides glucose and galactose. Coded by lacZ gene.
  3. β-Galactoside acetyltransferase transfers acetyl groups from the acetyl CoA to certain β-galactosides. Coded by lacA gene.
• Inducers are substances that stimulate the production of a inducible protein. (p. 330)
  • For example, lactose is an inducer; when it’s concentration is high, lactose binds to the lac repressor, thereby changing it’s the repressor’s conformation so the repressor falls off the operator on the DNA strand.
  • Note, the lac repressor protein is usually abbreivated lacI aka lowercase l-a-c and then capital I.
  • After the lactose-bound repressor falls off, RNAP can do it’s work and start expressing the lacZ, lacY, and lacA genes. And therefore, production of the aforementioned inducible enzymes β-Galactoside permease, β-Galactosidase, and β-Galactoside acetyltransferase is increased.
• In contrast, constitutive proteins are expressed all the time at a constant rate. (p. 330)
• A cluster of genes that share the same [promoter region](https://en.wikipedia.org/wiki/Promoter_(genetics) is called an operon. Thus, the three lactose-metabolism genes: lacY, lacZ, and lacA are all part of the same operon.
  • Several genes must be co-transcribed to define an operon.
  • In general, prokaryotic operons generate polycistronic mRNAs whereby a single mRNA codes for multiple proteins simultaneously. Eukaryotic operons usually express as monocistronic mRNAs aka one mRNA per polypeptide or protein.
  • The typical structure for an operon is: promoter, operator region, and then 2 or more structural genes. (p. 330)

Additional details of the lac operon

• Based on additional research, I believe that the more accurate model for the operon is the following sequence. For more details, scroll down to the middl of this Khan Academy page and see the first image on this page.
  1. Binding Site for CAP Activator
  2. Promoter region (where RNAP would initially attach)
  3. Operator region (RNAP needs to attach here as well, but can be blocked by LacI repressor)
  4. lacX
  5. lacY
  6. lacA

Types of Regulation covered

• An inducible operon regulated by a repressor protein (like lac repressor which will fall off of the operator region when lactose binds to the repressor)
• An repressible operon regulated by a repressor protein
• An operon regualted by an activator protein like CAP which is activated by the presence of cAMP.

The trp operon is a repressible regulatoin system

• Khan Academy article and video on trp operon
• Trp is a repressible system using a co-repressor in contrast to the lac operon which is an inducible system.