Lecture 02: Cell Chemistry and Macromolecules and Bioenergetics

The Chemical Basis of Life

• Organisms are quite uniform at the molecular level → Unity of Biochemistry!

  • Eg. Glycolysis: takes glucose and breaks it down to generate ATP

• Jacques Monod (1954) – Anything found to be true in E.Coli must also be true in Elephants.

The hierarchy in increasing complexity

Main Elements in Cells

• Life is dependent on chemical reactions in an aqueous environment both inside and outside the cell.

• A cell is formed from carbon compounds → generally in combination with nitrogen and oxygen (elements in red) → 99% of human body composition.

• Some elements are required in lower (blue, 0.9%) or trace amounts (yellow)

• Atomic number on periodic table is in upper left corner

• Atomic weight on periodic table is in the middle of each element

Atomic number on periodic table

is in upper left corner

Atomic weight on periodic table

is in the middle of each element

Molecules:

Two or more atoms in a definite arrangement held together by chemical bonds

Biomolecules:

• Molecules made by living organisms

• Mostly centred by carbon that can form single, double and triple bonds

Biomolecules centred around Carbon

• Carbon binds up to 4 other atoms

• Size and electronic structure is suited to generate large biological molecules

Covalent Bonds

• Carbon (C), Hydrogen (H), Nitrogen (N) and Oxygen (O) can be linked together by covalent bonds to form molecules.

• Atoms are most stable when their outermost electron shells are full

• Can share electrons to create a stable bond → Covalent Bonds

Polar Covalent Bonds

Unequal sharing of electrons

Asymmetric charge distribution:

One atom has a partial negative charge and the other atom has a partial positive charge

Electronegative atom:

atom with the greater attractive force is called the electronegative atom → attracts negative charge (electrons) from electropositive atom(s)

Non-Polar Covalent Bonds

• Equal sharing of electrons → lack electronegative atoms

• E.g. molecules made up entirely of C and H (ex Methane)

Non-Covalent Interactions

• Interactions between molecules or different parts of a large biomolecule

• Depend on shared attractive forces between atoms of opposite charge

Types of noncovalent interactions important in cells:

• Ionic bonds

• Hydrogen bonds

• Van der waals attractions

• Hydrophobic interactions

Ionic Bonds

• result of electrical attraction because of opposing charges. Involves transfer of electron(s) from one atom to the other.

• E.g. holds macromolecules together (DNA & protein): between positively charged nitrogen (protein) and negatively charged oxygen (DNA)

What gives DNA the negative charge

The phosphate group

Hydrogen Bonds

• weak bond, result of electrical attraction.

• Keeps important biomolecular structures like DNA together

• Polar molecules interact with other polar molecules, like water

• Heat will easily break hydrogen bonds (denaturing of dna)

• room temperature water having more energy, leading to the constant breaking and forming of hydrogen bonds, while in ice, the hydrogen bonds are largely stable due to the lower energy at colder temperatures.

Van der Walls Attraction

• Weak and nonspecific interaction between two atoms in close proximity.

• Temporary charges in nonpolar molecules = ‘dipoles’

• Form because electrons are constantly in motion

Hydrophobic Interactions

• uncharged non-polar molecules do not interact with polar molecules (e.g. water)

• Form clumps or aggregates to minimize exposure

• Not an actual bond

• Ex. Oil doesn’t dissolve in water

• Ex. Phospholipids, hydrophobic ends face the inward and hydrophilic face outward to aequous environment

Macromolecules:

• Chains of chemical units linked end-to-end → key to all cellular processes

• Ex. 70% of bacteria cell is water.

Macromolecules include

• DNA

• RNA

• Protein

• Polysaccharides

Monomers Make Up Macromolecules

• Monomers of macromolecules are joined together by covalent bonds.

• Macromolecules are polymers of building blocks known as monomers

• Polymers form by joining monomers → condensation (water is removed)

• Polymers are broken down into monomers → hydrolysis (water is added)

Sugars form

polysaccharides, glycogen, and starch (In plants)

Fatty acids form

fats and membrane lipids

Amino acids form

proteins

Nucleotides form

nucleic acids

Condensation

• Removes water

• Energetically unfavourable

Hydrolysis

• Add water

• Energetically favourable reaction

Functional Groups

• particular atom groupings that behave as a unit.

• These affect the properties of biomolecules (e.g. change chemical reactivity) because:

  • Contain electronegative atoms (N,O,P,S)

  • Can make molecules more polar or more reactive

  • May confer a positive or negative charge due to ionization

• Memorize functional groups

• Ex. Sulfhydral present in certain amino acids that form bonds with other proteins that also have sulfer = forming a disulphide bridge → important in joining subunits of protein

Biomolecules characteristics

• Biomolecules centred around Carbon → carbon binds up to 4 other atoms

• Long chains of carbon atoms used to construct biological molecules

• Linear, branched or cyclic

• Simplest group of biological molecules → hydrocarbons (C-H)

• Certain hydrogens is often replaced by “functional groups”

Carbohydrates

• General formula: (CH2O)n

• Important sugars in cell metabolism have 3-7 carbons

• 3 sugars = trioses; 4 sugars = tetroses; 5 sugars = pentoses; 6 sugars = hexoses

• Carbonyl internal position – forms ketone = ketose

• Carbonyl at one end – forms aldehyde = aldose

Carbonyl internal position – forms

ketone = ketose

Carbonyl at one end – forms

aldehyde = aldose

Monosaccharides – Closed Ring Structures

• Sugars with 5 or more carbons form a closed ring structure.

• Forms ring formation

Ring formation

in aqueous solution, the aldehyde or ketone group of a sugar molecule tends to react with a hydroxyl group of the same molecule, closing the molecule into a ring

Example: Glucose

• Glucose = 6-carbon ring

• OH of C1 projects below the plane of the ring - α-glucose

• OH of C1 projects up from the plane of the ring - β-glucose

• As soon as one sugar is linked to another the alpha and beta form is frozen

α-glucose

OH of C1 projects below the plane of the ring

β-glucose

OH of C1 projects up from the plane of the ring - β-glucose

Isomers

• Same formula but different arrangement

• ex. Glucose, galactose and mannose have the same formula (C6H12O6) but differ in arrangement of groups around one or two atoms

• The small differences make only minor changes in the chemical properties of the sugar. But they are recognized by enzymes and other proteins and therefore can have major biological effects

Carbohydrate Polymers

• Covalent bond formed between C1 of one sugar and hydroxyl (OH) of another sugar

• Generates C-O-C linkage between sugars

Disaccharides:

Two monosaccharides covalently bonded together → energy storage, e.g., sucrose, maltose, lactose

Oligosaccharides:

a small chain of sugars → when attached to lipids or proteins = glycolipids or glycoproteins

Polysaccharides:

• a long chain of sugars

• very large molecules with a structural or storage function

• E.g.: chitin (structural) , cellulose, starch, glycogen (in liver, and we can survive off just glycogen for 48 hrs. )

Glycogen and Starch contain

• α(1,4) linkages resulting in long, branched chains (glycogen) or coils (starch).

• Glycogen or starch granules (where the arrow is pointing) can be broken down to get glucose

Cellulose contains

β(1,4) linkages resulting in long branches.

Lipids

• A large group of nonpolar biological molecules → dissolve in organic solvents but not in water (lack polar groups = hydrophobic)

• Composed mainly of C,H and O

• Lipids with important cell functions: fats, phospholipids, steroids

3 types of lipids

• Triglycerides

• Phospholipids

• Steroids and waxes

Fats = triacylglycerol

= glycerol + 3 fatty acids

Lipids – Fatty Acids

• long hydrocarbon chains with a single carboxyl (COOH) at one end

• Vary in length

Fatty acid with No double bonds

• saturated

  • Can be solid

Fatty acid with Double bonds

• unsaturated

  • This double bond is rigid and creates a kink and bending in the chain. The rest of the chain is free to rotate about the the other C-C bonds

  • They can’t pack as tightly.

  • Important in plasma membrane where things need to move around

  • Liquid state

Triacylglycerols

• Form large spherical fat droplets in the cell cytoplasm

• Molecules don’t have a change in an aqueous environment → cluster together

What links fatty acids to glycerol to form triacylglycerol

Ester bonding

Esters

Are formed by combining an acid and an alcohol with byproduct of alcohol

Lipids – Steroids

• Complex ring structures → 4 hydrocarbon rings

• E.g.: Cholesterol = important animal plasma membrane component

• Building blocks of many steroid hormones

• Not present in plant cells → cholesterol- free

Lipids – Phospholipids

• Composed of glycerol + 2 fatty acids + phosphate group

• Major component of plasma and organelle membranes

• Hydrophilic on one end and hydrophobic on the other → amphipathic (polar head group and non polar tail)

• Positively charged choline group attached to the phosphate = phosphatidyl choline

Lipid bilayers are formed by

phospholipids

DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are

polymers of nucleotides

Nucleotides

5-carbon sugar + nitrogenous base + phosphate

Nucleosides

5-carbon sugar + nitrogenous base (no phosphate)

What type of sugar does DNA have

deoxyribose sugar

What type of sugar does RNA have

ribose sugar

Purines

• adenine (A) and guanine (G)

• Double ring structure

Pyrimidines

• cytosine (C) and thymine (T) in DNA

• T is replaced by Uracil in RNA

• Single ring

Nucleotides And phosphodester bond

• Nucleotides are joined by sugar-phosphate linkages

• 3’ hydroxyl attached to 5’phosphate of the adjoining nucleotide → phosphodiester bond

Base pairing → hydrogen bond

• DNA double helix formed by base pairing of a purine with a pyrimidine

• A bonds with T = 2 hydrogen bonds

• G bonds with C = 3 hydrogen bonds

A bonds with

• T = 2 hydrogen bonds

• Bond will break faster and easier than G-C bonds because of one less hydrogen bonds

G bonds with

C = 3 hydrogen bonds

Nucleotides serve multiple functions

Proteins

• About ~ 1 x 104 proteins made in every mammalian cell per second!

• Carry out almost all cellular functions. For example:

  • Enzymes - accelerate chemical reactions in the cell

  • Signaling - kinases, phosphatases are involved (initiate reactions that lead to another reaction)

  • Hormones - long range messenger molecules

  • Growth factors

  • Membrane receptors - communication between cells

  • Cell movement - cytoskeleton

Amino Acids

• Composed of H, C, O, N and also S or P

• 20 different types

• Amino (NH2) and Carboxyl (COOH) groups

• These groups are separated by a single carbon (α-carbon)

• R groups (side chains) give amino acids their variability

R - Groups

• Four categories of R groups:

  • Polar charged: form ionic bonds

  • Polar uncharged: form H bonds

  • Nonpolar

  • Other e.g. sulfhydryl or cysteine

• MEMORIZE THE 14 AMINO ACIDS codes

How does cell know which order to put amino acids in

mRNA

What dictates the sequence of mRNA

DNA

Cysteine amino acids can

form disulfide bonds in oxidizing conditions

Peptide Bonds

• Carboxyl group of one amino acid becomes attached to the amino group of another

• Join amino acids

• Forms polypeptide chains → proteins

What forms peptide bonds in cells

Ribosomes use energy to form this bond, then do elongation

Macromolecules can assemble in complexes

• Important reason for complexes is when everything is in close proximity is in the cell.

• By bringing all the necessary components of a biological process together in a single, coordinated protein complex, the cell can dramatically increase the speed, efficiency, and specificity of its functions.

Macromolecule Synthesis and Breakdown

• reversing disorder is not spontaneous

  • total entropy of an isolated system can only increase over time; it can never spontaneously decrease.

• Second law of thermodynamics → cannot reverse the state of a system without increasing entropy of surrounding

• Need release of heat (energy conversion)

Metabolism

Anabolic and catabolic pathways

Anabolism

the synthesis of complex molecules in living organism from simpler ones together with the storage of energy

Catabolism

• Break down larger molecules to smaller usable units for biosynthesis

• Produce useful forms of energy

• Use energy in anabolic pathways to make other molecules

Catalysts and Cell Metabolism

• Cell metabolism pathways comprise many enzymes.

• Ex glycolysis has 7 main steps

How Enzymes Work

• Enzymes (catalysts) do not change during reaction.

• Enzymes bring down the energy barrier

• Enzyme (it’s a protein) has an active site. The active site is a specific organization of amino acid into a 3D shape, such that substrate can fit into the pocket

• The substrate fits very tightly and formed enzyme substrate complex

• Carry out catalysis

• Now have enzyme product complex.

• Product get released and enzyme has an empty active site again

• Enzyme doesn’t get used just recycled

• This cycle continues until protein gets degraded

Enzymes Can Drive Specific Pathways

• Enzyme catalyzed reactions can reach equilibrium much faster.

• Uncatalyzed reaction at equilibrium. The units (Y) will form X

  • Not a whole lot is made. There are also unfavourable reverse reactions occurring

• Enzyme catalyzed reaction at equilibrium: drives the reaction in one direction. No more reverse reactions

Enzymes Reduce Activation Energy Barriers

• Reduced activation energy barriers → increased probability of reaction.

• Allows for chemical reactions to proceed at normal temperatures

• Lowered energy activation means this reaction will occur easier, and faster

Enzymes Cannot Force Energetically Unfavourable Reactions

• ∆G (Gibbs free energy) is a measure of the change in the amount of energy available to do work.

• Favourable reactions decrease the ∆G (negative ∆G), release energy and increase the disorder of the surroundings. → occurs spontaneously

• Unfavourable reactions increase the ∆G (Positive ∆G), require energy and decrease the disorder of the surroundings → only occurs if it is coupled to a second energetically favourable reactions

Favourable reactions

decrease the ∆G (negative ∆G), release energy and increase the disorder of the surroundings. → occurs spontaneously

Unfavourable reactions

• increase the ∆G (Positive ∆G), require energy and decrease the disorder of the surroundings → only occurs if it is coupled to a second energetically favourable reactions

• This will not happen naturally or spontaneously

Cells Utilize Reaction Coupling

• Use an energetically favourable reaction to drive an energetically unfavourable reaction

• Free energy change < 0 (disorder of surroundings increases)

• Energy carrier is the truck below