L2 - Macromolecules

Covalent Bonds

• Covalent bonds are principal forces that hold atoms together by sharing electrons equally.

• These bonds are strong and crucial for the stability of macromolecules like DNA and the cytoskeleton.

• Macromolecules need to be stable and not spontaneously degrade.

• Covalent bonds are very strong, however, they don't break under conditions where life exists (temperature, physical conditions).

• Breaking covalent bonds requires energy and catalysts (enzymes, specifically proteins).

• Single, double, and triple bonds exist, with triple bonds being the hardest to break.

Nitrogen Fixation Example

• Dinitrogen gas has a triple bond that is difficult to break.

• Nitrogen enters ecosystems, especially oceans, through nitrogen fixation.

• Specialized microbes, like certain cyanobacteria, break the triple nitrogen bond using specific enzymes and energy.

• This process is essential for making nitrogen available to other life forms.

• There are constraints to life and ecosystems regarding breaking very strong bonds.

Polar Covalent Bonds and Hydrogen Bonds

• Unequal sharing of electrons, such as in oxygen-hydrogen bonds, creates partial charges (e.g., slightly positive hydrogen and slightly negative oxygen).

• Water's polarity due to polar covalent bonds is vital for life, allowing it to interact with other polar or charged molecules, making them soluble within cells.

Noncovalent Bonds (Hydrogen Bonds)

• Hydrogen bonds are weak interactions between electronegative atoms and positive hydrogen atoms.

• They are essential for biological molecules that need to attach and detach at different times.

• Example: DNA double helix is stabilized, but the bases are linked through hydrogen bonds, allowing it to be broken apart during replication.

Macromolecule Formation and Regulation

• There are four major families of small organic molecules and therefore four families of macromolecules

  • Sugars → Polysaccharides

  • Fatty acids → Fats/Lipids/Membranes

  • Amino acids → Proteins

  • Nucleotides → Nucleic acids

• Tiny organic molecules are linked by covalent bonds to form larger macromolecules (e.g., DNA strands, ribosomes).

• Noncovalent bonds (hydrogen bonds) enable macromolecules to function in different configurations.

• This is crucial for molecular regulation of the cell, including processes like replication, transcription, and translation.

• Water's solvent properties are important for interactions between organic molecules in aqueous environments.

• At physiologically relevant temperatures, some molecules have sufficient energy to break hydrogen bonds (e.g., DNA replication).

Uniformity in Biochemical Reactions

• Covalent bonds are essential for the stability of macromolecules.

• The same biochemical reaction is used to form all classes of macromolecules.

• After long chains are formed, they can interact through hydrogen bonds.

Macromolecules and Subunits

• Macromolecules are complex organic molecules with building blocks or subunits linked by covalent and non-covalent bonds.

• Subunits include sugars, fatty acids, amino acids, and nucleotides.

• The first three (sugars, fatty acids, and amino acids) are focused on in this lecture, while nucleotides will be discussed later.

• Small organic molecules (subunits) are called monomers, while many monomers linked together form a polymer.

• Linking sugars creates polysaccharides.

Polymer Formation

• Macromolecules form by linking subunits, with repeated units forming polymers.

• Some polymers have identical units (e.g., glucose in starch and glycogen), serving as energy storage for cells.

• Proteins have slightly different amino acid subunits with varying chemical properties affecting their interactions and 3D structure.

Making and Breaking Polymers

• Cells efficiently repurpose organic material by continuously manufacturing and degrading macromolecules.

• Biochemical processes for making and breaking polymers are similar across different macromolecules, even with different monomers.

Condensation and Hydrolysis

• Condensation (Dehydration) Reaction: Forms a covalent bond by removing water.

• Hydrolysis: Consumes water to break apart polymers.

• Both of these processes occur at the expense of energy in the form of ATP and are mediated by enzymes.

• Monomers have a hydroxyl group, and the remaining polymer has a hydrogen, and both are needed to form water during condensation.

Sugars (Carbohydrates)

• Sugars are essential organic molecules involved in cellular bioenergetics.

• Energy is stored in long polymers of glucose, the monomers of which are monosaccharides.

• Glucose is a major molecule in respiration, a six-carbon sugar.

• Formula: $(CH_{2}O)_6$.

• Six-carbon sugars (e.g., glucose) are commonly used in cell metabolism.

Disaccharides and Polysaccharides

• Two monomers join to form a disaccharide through dehydration, forming a covalent (glycosidic) bond.

• Enzymes like lactase break the glycosidic bond in lactose into glucose and galactose.

• Lactose intolerance results from a deficiency in lactase, causing lactose buildup.

• Long chains of sugars (thousands of monomers) form polysaccharides like glycogen (animal starch), stored in muscles, liver, and brain.

• Starch in plants is another energy store made of glucose polymers.

• Cellulose provides structural support for plant cells.

Paleoproxy Example: Sugars in Algae

• Stable macromolecules allow earth scientists to use them as paleoproxies.

• Research on sugars stored in calcium carbonate shells of algae (Emiliania huxleyi) reveals past environmental conditions.

• E. huxleyi uses polysaccharide templates to build shells; changes in polysaccharide composition under different $pCO_2$ conditions.

• Changes in polysaccharide composition serve as a proxy for past $pCO_2$ concentrations.

• Polysaccharides are stable in sediments and can be analyzed to estimate past $pCO_2$ levels.

Hydrophilic vs. Hydrophobic

• Cells are primarily water (70% of cell mass).

• Hydrogen bonds form with polar molecules, making water a good solvent.

• Cells compartmentalize chemical reactions and separate internal from external environments.

• Water interacts with polar substances, causing them to dissolve readily and form hydrogen bonds.

• Hydrophilic Compounds: Form hydrogen bonds with water (e.g., amines, ketones).

• Hydrophobic Compounds: Nonpolar bonds (e.g., hydrocarbons) that are insoluble in water and interact with other nonpolar molecules.

Fatty Acids and Lipids

• Lipids are macromolecules grouped by their hydrophobicity. However, unlike polysaccharides, proteins, and nucleic acids, they are not polymers.

• They are insoluble in water but soluble in oils or organic solvents. This property makes them ‘grouped’.

• Many fatty acids have long hydrocarbon tails (hydrophobic chains of carbon and hydrogen atoms).

• They include a hydrophilic part made of carboxylic acid that is slightly charged.

• Fatty acids act as energy stores and components of cell membranes.

Fat Formation

• Fatty acids attach to glycerol (prop-1,2,3-triol, a three-carbon alcohol) via condensation reactions, removing water and forming covalent bonds.

• A true fat (triglyceride) has fatty acids attached to each carbon of the glycerol backbone and hydroxyl group.

• A fatty acid has a long carbon chain skeleton with a carboxyl group on one end, but it is the hydrocarbon chain that makes these molecules hydrophobic.

Energy Reserve

• Fats serve as concentrated energy reserves for organisms, providing more usable energy than glucose when metabolized (six times the amount).

• Multicellular organisms use fat stores during hibernation or periods without food.

Phospholipids

• Phospholipids are similar to fats in the sense that they have a glycerol and 2 fatty acids, but rather than a third fatty acid, they have a phosphate group which is bonded to the third hydroxyl group.

• This phosphate group is negatively charged, which can cause additional small (usually charged or polar) molecules to be linked to the phosphate group to form a variety of phospholipids

• Phosphate group is negative charge and has a slight affinity for water, making it hydrophilic.

• This structure includes a hydrophobic part consisting of a hydrocarbon tail and a hydrophobic part.

Bilayer Formation

• In aqueous solutions, phospholipids self-assemble into bilayers (aka membranes) with hydrophobic tails facing inward and hydrophilic heads facing outward. This is stable as it separates the hydrophobic fatty acids from the water while keeping the hydrophilic phosphate head next to the water.

• This bilayer structure separates two aqueous regions effectively.

• The formation is driven by the tendency to be more in touch with the similar hydrophilic or hydrophobic substances.

• Hydrocarbon tails excludes water and forms the core separating the two aqueous regions.

• That is a very difficult barrier for polar or charged molecules to go through.

• It also forms a boundary between the external environment and the major components of the cell.

Cell Membranes

• Spherical phospholipid bilayers encase cells, providing a boundary between the external environment and cell components.

• Proteins embedded in the bilayer regulate the passage of substances that cannot pass through the hydrophobic core.

Paleoproxy Example: Membrane Lipids and TEX₈₆

• Lipids are found in living cells and can be preserved in the sedimentary record.

• TEX₈₆ is a palaeo thermometer for used by scientists for Archaea lipid membranes and is sensitive to temperature.

• It serves as a paleo thermometer so that these lipids that are embedded in this make up these these membranes in the archaea are quite sensitive to changes in temperature.

• These various cyclic structures allows to discriminate between these different forms, and the TEX₈₆ is basically looking at the ratio of these because they found that under different temperature conditions, under different growth conditions, the archaea tends to modify its lipids, which is thought to be tied their physiology.

• The proxy is used to estimate sea surface temperatures based on archaea membrane lipids.

• The relationship between TEX₈₆ and sea surface temperature works in low to kind of temperate latitudes (equator to forty, fifty degrees).

• Factors influencing proxy variability: organism, terrestrial runoff

Redfield Ratio

• This oceanographer came up with a ratio of these elements in organic matter and in algae.

• The stoichiometry of life reflects elemental ratios (C:N:P) in organic matter, typically carbon based ratio of 106:16:1.

• Nitrogen is from protein and phosphate is from phospholipds.

Phosphate Limitation and Sulfolipids

• In oligotrophic gyres (ocean deserts like around Hawaii), phosphate is limited, restricting productivity.

• Some cyanobacteria adapt by using sulfolipids instead of phospholipids to circumvent phosphate limitation.

• These low conditions can influence the composition of organism

• These modifications of different ratios modify understanding of the redfield ration.

• Switching to sulfolipids modifies elemental ratios (N:P becomes more elevated) and impacts biogeochemical models.

• This highlights how biology can adapt to elemental limitations and modify elemental ratios.