Lecture series D1

“Basics of biochemistry and metabolism”

notes based on Alberts et al 4^th ed. (2002) Chapter 2

prepared by T. J. Newman, September 17-25, 2005

revised, September 24, 2006

this document not for public use – all images copyright Garland Science Publishing 2002

BIOCHEMISTRY

· We can view an organism as a complex “chemical system” – based on carbon compounds

· Cells are 70% water, and so reactions occur almost exclusively in aqueous environment

· Most carbon atoms in a cell are incorporated in very large organic macromolecules

ELEMENTS IN BIOLOGY

· Relatively few elements are used in the construction of cells.

· The primary four are carbon (C), hydrogen (H), nitrogen (N), and oxygen (O) – these make up 96.5% of an organism’s weight.

· Other important elements are calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), phosphorus (P), sulphur (S), and chlorine (Cl).

· Atoms form molecules, and the physics of these is controlled by the outer electrons – in particular, how many electrons are missing from the outer shell.

IONIC AND COVALENT BONDS

· Atoms with half-filled shells are highly reactive – e.g. hydrogen, and carbon.

· The two common types of chemical bond are “ionic bonds” and “covalent bonds.”

· In ionic bonds, an atom transfers electrons to another atom in order to allow each atom to have a filled outer shell.

o Thus both atoms become charged (with equal and opposite charge), and attract one another to form a molecule (with a strong ionic bond).

o The classic example of ionic bonds is Na Cl – table salt – which is formed from a crystal lattice of Na-Cl pairs.

o Since ionic bonds are formed from ions, and ions interact strongly with water molecules, salts are easily dissolved in water.

o This is not true of covalent bonds.

· In a covalent bond, two atoms share an electron (or electrons), in an attempt to satisfy their unfilled outermost shell.

· If the sharing of electrons in a covalent bond is unequal between the two atoms concerned, the bond is said to be polarized, since the resulting molecule will have a dipole moment.

· Covalent bonds have an equilibrium bond length, and bond strength – this latter is about 100 times the typical energy of thermal fluctuations at room temperature.

o Relative to thermal energies, a covalent bond releases a great deal of energy when broken.

o Bond-breaking is generally controlled by specific catalysts, called enzymes.

· The number of covalent bonds a given element can make depends on its valence.

o This is 1,2,3, and 4 for H, O, N, and C respectively.

o Multiple bonds have a characteristic relative orientation, which gives molecules characteristic three-dimensional shape (e.g. C has four bonds forming a tetrahedron).

· Most covalent bonds involve one electron from each atom – such a bond is called a single bond and allows the atoms to rotate relative to one another.

· Double bonds involve two electrons from each atom, and are rigid – giving molecules a planar geometry.

· Polar covalent bonds create dipole moments, which then allow molecules to interact (weakly) with one another.

o A classic example of this is hydrogen bonding between water molecules.

· Atoms can also be attracted to each other through the weak van der Waals force, caused by fluctuation in the electron density of each atom, giving rise to a weak dipole-dipole interaction.

WATER

· In a water molecule, two hydrogen atoms are covalently bonded to an oxygen atom.

o Each bond is highly polar, since O is strongly attractive to electrons compared to H.

o The H atoms have a preponderance of + charge, and O a preponderance of – charge.

o Hydrogen bonding occurs between water molecules, with the (+)H atom of one water molecule bonding weakly with the (–)O atom of another molecule.

· Hydrogen bonds are weak so are constantly formed and broken in water at room temperature – forming transitory clusters of water molecules.

· Charged molecules or ions interact favorably with water, and are termed hydrophilic.

o Examples of such molecules are sugars, RNA, DNA, and most proteins.

· Uncharged molecules do not form hydrogen bonds and do not dissolve easily in water.

o Examples of such hydrophobic molecules are hydrocarbons (made from covalent C-H bonds which are not polar).

· A molecule possessing a highly polar bond between an H and another atom will give up its weakly bound H atom (ion when dissociated) when dissolved in water.

· The proton will couple with the electronegative region surrounding the O of a water molecule, thus forming a hydronium ion (H₃O⁺).

o The reverse reaction occurs easily too.

· Such molecules are termed acids.

· The higher the concentration of H₃O⁺ the more acidic the solution.

o In pure water, the concentration of H₃O⁺ is 10^-7 M (meaning 10^-7 times Avogadro’s number of ions per liter).

o This corresponds to pH 7.

o The pH value is –log₁₀ of the molar concentration of hydronium ions.

· In contrast, some molecules strip an H from a water molecule forming a hydroxyl ion (OH^-).

· Such molecules are called bases (or alkalines).

o An important class of bases is that containing an NH₂ group, which forms NH₃⁺ and OH^- when dissolved in water.

o Hydroxyl ions combine with hydronium ions to form water, and so bases raise the pH of the solution.

NON-COVALENT INTERACTIONS IN CELLS

Bond type	Length (nm)	Strength in vacuum (kcal/mole)	Strength in water (kcal/mole)
Covalent	0.15	90	90
Ionic	0.25	80	3
Hydrogen	0.30	4	1
Van der Waals	0.35	0.1	0.1

· Covalent bonds are far stronger than other interactions in water – so the integrity of molecules is assured.

· However, interactions between molecules are dictated by other types of interactions:

ionic – weaker in water due to screening

hydrogen bonds – e.g. in water, but also between other molecules, when an electropositive hydrogen atom is shared by two electronegative atoms

van der Waals interactions – already discussed

hydrophobic forces – non-polar regions of molecules can form weak attractive bonds, as the non-polar regions are hydrophobic, and this effect can be minimized by bringing such regions into close contact – this effect is important for correct folding of proteins.

IMPORTANT SUB-MOLECULAR GROUPS AND FAMILIES OF MOLECULES

· Carbon is central to the formation of biomolecules.

· It can covalently bond to four atoms, and this allows a large array of molecular types to be formed.

· Important groups that are used in the formation of larger molecules are:

o methyl (-CH₃),

o hydroxyl (-OH),

o carboxyl (-COOH),

o carbonyl (-C=O),

o phosphate (-PO₃^2-),

o amino (-NH₂).

· The cell contains four major families of small organic molecules.

· These molecules either exist singly in solution, and are used for signaling or as energy sources…

· … or else, in far greater numbers, they assemble into larger macromolecules.

· The four families of small molecules are sugars, fatty acids, amino acids, and nucleotides.

· When assembled into large macromolecules, these families create, respectively, polysaccharides, fats and lipids, proteins, and nucleic acids.

SUGARS

· Simplest sugars (monosaccharides) have the formula (CH₂O)_n (which explains the name carbohydrates).

o e.g. glucose has formula C₆H₁₂O₆

· Note, sugar molecules can bond in a large number of different isomers (rearranging glucose gives mannose or galactose…)

o Sugars can exist in two forms – the D and L forms, which are mirror images (optical isomers)

· Sugars exist in either ring or chain forms, and contain additional hydroxyl groups, and an aldehyde or ketone group

o The aldehyde or ketones can react with hydroxyl groups to form rings, and connect monosaccharides to form disaccharides.

o These can bond further to form oligosaccharides (short chains), or even very large polysaccharides (long chains), composed of thousands of monosaccharides.

· Glucose is a fundamental monosaccharide.

o It can be broken down by a complex set of reactions to give energy to the cell.

o Polysaccharides composed of glucose subunits (e.g. glycogen) are used by organisms as long-term stores of energy.

· Sugars are also used for structural purposes in cells.

o e. g. cellulose is a polysaccharide of glucose

o glycolipids and glycoproteins have a range of functions in cell membranes

o most cells have a surface covered in sugar polymers

FATTY ACIDS

· Fatty acids have two distinct chemical regions:

o long hydrophobic hydrocarbon tail

o a carboxyl (-CO OH) group, acting as carboxylic acid, which is extremely hydrophilic

o the carboxylic acid group chemically links the fatty acid to other molecules

· Figure shows palmitic acid – the carbons are saturated with hydrogens

· unsaturated fatty acids have double bonds in the hydrocarbon tail, which makes them kinked and unable to pack into a solid mass

· fatty acids are a concentrated energy source – contain six times more energy (weight for weight) than glucose

o stored in the cytoplasm in triacylglycerol molecules (three fatty acids joined to a glycerol molecule)

o fatty acids are a subset of lipids – water insoluble molecules

· the primary function of fatty acids is in the construction of cell membranes

o these are typically formed from phospholipids (two fatty acids joined to a glycerol molecule)

o the glycerol is also joined to a phosphate group, which is part of the hydrophilic head

o molecules with both hydrophilic and hydrophobic regions are called amphipathic

· two layers of phospholipids can form a sandwich with the hydrophobic tails on the interior

· this is the lipid bilayer – the structural basis for cell membranes

AMINO ACIDS

· defining characteristic of amino acids:

o carboxylic acid group and an amino group, both linked to a single (alpha) carbon atom

o variety comes from the many different side groups attached to the alpha carbon

· polymers formed from amino acids are used to make proteins

o a given chain folds into a unique three-dimensional structure

· covalent bonds between amino acids are called peptide bonds (protein = polypeptide)

· polypeptide has amino group at one end, and carboxyl group at the other (example below)

· all proteins used in life are composed of sequences of 20 different amino acids

o why these 20 were “chosen” is a mystery

· as with sugars, amino acids exist as optical isomers, in D and L forms

o only L forms are found in proteins – this is another mystery

· within the 20 amino acids there are sub-families of chemical groups:

o acidic side chains:

§ aspartic acid Asp D

§ glutamic acid Glu E

o basic side chains:

§ lysine Lys K

§ arginine Arg R

§ histidine His H

o uncharged polar side chains

§ asparagines Asn N

§ glutamine Gln Q

§ serine Ser S

§ threonine Thr T

§ tyrosine Tyr Y

o nonpolar side chains

§ alanine Ala A

§ valine Val V

§ leucine Leu L

§ isoleucine Ile I

§ praline Pro P

§ phenylalanine Phe F

§ methionine Met M

§ tryptophan Trp W

§ glycine Gly G

§ cysteine Cys C

NUCLEOTIDES

· a nucleotide is made from an N-containing ring compound linked to a five-carbon sugar

o the sugar can be either ribose or deoxyribose (ribose missing an O), and carries one or more phosphate groups

o nucleotides containing ribose are termed ribonucleotides

o nucleotides containing deoxyribose are termed deoxyribonucleotides

· the N-containing ring is termed a base, as it can absorb an H ion in solution

o the bases have one of two forms:

§ pyrimidines (six-sided ring)