• The life of a cell depends on thousands of chemical interactions and reactions

• Water is the most abundant molecule in biological systems with 70-80% of weight in most cells

• 7% of the weight is living matter composed of inorganic ions and small molecules (amino acids, nucleotides, and sugars)

• Many biomolecules (e.g., sugars) readily dissolve in water; these water-liking molecules are described as hydrophilic

• Other biomolecules (e.g., fats like triacylglycerols) shun water; these are said to be hydrophobic (water-fearing).

• Still, other biomolecules (e.g., phospholipids), referred to as amphipathic, are a bit schizophrenic, containing both hydrophilic and hydrophobic regions

• These are used to build the membranes that surround cells and their internal organelles

• The smooth functioning of cells, tissues, and organisms depends on all these molecules, from the smallest to the largest

• The chemistry of the simple proton (H+) with a mass of 1 dalton (Da) can be as important to the survival of a human cell as that of each gigantic DNA molecule with a mass as large as 8.6 x 1010 Da

2.1 - Atomic Bonds and Molecular Interactions

• Strong and weak attractive forces between atoms are the glue that holds them together in individual molecules and permits interactions between different biological molecules

• Strong forces form a covalent bond when two atoms share one pair of electrons (“single” bond) or multiple pairs of electrons (“double” bond, “triple” bond, etc.)

• The weak attractive forces of noncovalent interactions are equally important in determining the properties and functions of biomolecules such as proteins, nucleic acids, carbohydrates, and lipids

• There are four major types of noncovalent interactions: ionic interactions, hydrogen bonds, van der Waals interactions, and the hydrophobic effect

Each Atom Has a Defined Number and Geometry of Covalent Bonds

• Hydrogen, oxygen, carbon, nitrogen, phosphorus, and sulphur are the most abundant elements found in biological molecules

  • These atoms, which rarely exist as isolated entities, readily form covalent bonds with other atoms, using electrons that reside in the outermost electron orbitals surrounding their nuclei

• As a rule, each type of atom forms a characteristic number of covalent bonds with other atoms, with a well-defined geometry determined by the atom’s size and by both the distribution of electrons around the nucleus and the number of electrons that it can share

• Sometimes (e.g., carbon), the number of stable covalent bonds formed is fixed; in other cases (e.g., sulphur), different numbers of stable covalent bonds are possible

• All the biological building blocks are organized around the carbon atom, which normally forms four covalent bonds with two to four other atoms

• As illustrated by the methane (CH4) molecule, when carbon is bonded to four other atoms, the angle between any two bonds is 109.5o and the positions of bonded atoms define the four points of a tetrahedron

• This geometry helps define the structures of many biomolecules

• A carbon (or any other) atom bonded to four dissimilar atoms or groups in a nonplanar configuration is said to be asymmetric

• The tetrahedral orientation of bonds formed by an asymmetric carbon atom can be arranged in three-dimensional space in two different ways

  • Producing molecules that are mirror images of each other, a property called chirality

• Such molecules are called optical isomers, or stereoisomers

• Many molecules in cells contain at least one asymmetric carbon atom, often called a chiral carbon atom

• The different stereoisomers of a molecule usually have completely different biological activities because the arrangement of atoms within their structures differs, yielding their unique abilities to interact and chemically react with other molecules

• Carbon can also bond to three other atoms in which all atoms are in a common plane

  • The carbon atom forms two typical single bonds with two atoms and a double bond (two shared electron pairs) with the third atom

• In the absence of other constraints, atoms joined by a single bond generally can rotate freely about the bond axis, while those connected by a double bond cannot

• The rigid planarity imposed by double bonds has enormous significance for the shapes and flexibility of large biological molecules such as proteins and nucleic acids

• A hydrogen atom forms only one bond

• An atom of oxygen forms only two covalent bonds (usually) but has two additional pairs of electrons that can participate in noncovalent interactions

• Sulphur forms two covalent bonds in hydrogen sulphide (H2S), but also can accommodate six covalent bonds, as in sulfuric acid (H2SO4) and its sulphate derivatives

• Nitrogen and phosphorus each have five electrons to share

• In ammonia (NH3), the nitrogen atom forms three covalent bonds; the pair of electrons around the atom not involved in a covalent bond can take part in noncovalent interactions

• In the ammonium ion (NH4), nitrogen forms four covalent bonds, which have a tetrahedral geometry

• Phosphorus commonly forms five covalent bonds, as in phosphoric acid (H3PO4) and its phosphate derivatives, which form the backbone of nucleic acids

• Phosphate groups attached to proteins play a key role in regulating the activity of many proteins, and the central molecule in cellular energetics, ATP, contains three phosphate groups

Electrons are Shared Unequally in Polar Covalent Bonds

• Many molecules, the bonded atoms exert different attractions for the electrons of the covalent bond, resulting in unequal sharing of the electrons

• The extent of an atom’s ability to attract an electron is called its electronegativity

• A bond between atoms with identical or similar electronegativities is said to be nonpolar

• In a nonpolar bond, the bonding electrons are essentially shared equally between the two atoms, as is the case for most COC and COH bonds

• However, if two atoms differ in their electronegativities, the bond between them is said to be polar

• One end of a polar bond has a partial negative charge, and the other end has a partial positive charge

• In an OOH bond, for example, the greater electronegativity of the oxygen atom relative to hydrogen results in the electrons spending more time around the oxygen atom than the hydrogen

• Thus the OOH bond possesses an electric dipole, a positive charge separated from an equal but opposite negative charge

• We can think of the oxygen atom of the OOH bond as having, on average, a charge of 25 percent of an electron, with the H atom having an equivalent positive charge

  • Because of its two OOH bonds, water molecules (H2O) are dipoles that form electrostatic, noncovalent interactions with one another and with other molecules

• These interactions play a critical role in almost every biochemical interaction and are thus fundamental to cell biology

• The polarity of the OUP double bond in H3PO4 results in a “resonance hybrid”

Covalent Bonds Are Much Stronger and More Stable Than Non-Covalent Interactions

• Covalent bonds are very stable because the energies required to break them are much greater than the thermal energy available at room temperature (25oC) or body temperature (37oC)

• Consequently, at room temperature (25 oC), fewer than 1 in 1012 ethane molecules is broken into a pair of ·CH3 radicals, each containing an unpaired, nonbonding electron

• Covalent single bonds in biological molecules have energies similar to that of the COC bond in ethane

• Because more electrons are shared between atoms in double bonds, they require more energy to break than single bonds

• The energy required to break non-covalent interactions is only 1–5 kcal/mol, much less than the bond energies of covalent bonds

• Noncovalent interactions are weak enough that they are constantly being formed and broken at room temperature

• Although these interactions are weak and have a transient existence at physiological temperatures (25–37oC)

  • Multiple noncovalent interactions can act together to produce highly stable and specific associations between different parts of a large molecule or between different macromolecules

• We first review the four main types of noncovalent interactions and then consider their role in the binding of biomolecules to one another and to other molecules

Ionic Interactions Are Attractions Between Oppositely Charged Ions

• Ionic interactions result from the attraction of a positively charged ion—a cation—for a negatively charged ion—an anion

• In sodium chloride (NaCl), for example, the bonding electron contributed by the sodium atom is completely transferred to the chlorine atom

• Ionic interactions do not have fixed or specific geometric orientations because the electrostatic field around an ion---its attraction for an opposite charge—is uniform in all directions

• In aqueous solutions, simple ions of biological significance, such as Na+, K+, Ca2+, Mg2+, and Cl-, do not exist as free, isolated entities

• Each is hydrated, surrounded by a stable shell of water molecules, which are held in place by ionic interactions between the central ion and the oppositely charged end of the water dipole

• Most ionic compounds dissolve readily in water because the energy of hydration, the energy released when ions tightly bind water molecules, is greater than the lattice energy that stabilizes the crystal structure

• Parts or all of the aqueous hydration shell must be removed from ions when they directly interact with proteins

• The relative strength of the interaction between two ions, A and C, depends on the concentration of other ions in a solution

• The higher the concentration of other ions (e.g., Na and Cl), the more opportunities A and C have to interact ionically with these other ions, and thus the lower the energy required to break the interaction between A and C

• Resulting in increasing the concentrations of salts such as NaCl in a solution of biological molecules can weaken and even disrupt the ionic interactions holding the biomolecules together

Hydrogen Bonds Determine Water Solubility of Uncharged Molecules

• A hydrogen bond is the interaction of a partially positively charged hydrogen atom in a molecular dipole (e.g., water) with unpaired electrons from another atom, either in the same (intramolecular) or in a different (intermolecular) molecule

• Normally, a hydrogen atom forms a covalent bond with only one other atom

• However, a hydrogen atom covalently bonded to an electronegative donor atom D may form an additional weak association, the hydrogen bond, with an acceptor atom A, which must have a nonbonding pair of electrons available for the interaction

• Hydrogen bonds are both longer and weaker than covalent bonds between the same atoms

• The strength of a hydrogen bond between water molecules (approximately 5 kcal/mol) is much weaker than a covalent OOH bond (roughly 110 kcal/mol), although it is greater than that for many other hydrogen bonds in biological molecules (1–2kcal/mol)

• The extensive hydrogen bonding between water molecules accounts for many of the key properties of this compound, including its unusually high melting and boiling points and its ability to interact with many other molecules

• The solubility of uncharged substances in an aqueous environment depends largely on their ability to form hydrogen bonds with water

• In general, molecules with polar bonds that easily form hydrogen bonds with water can readily dissolve in water; that is, they are hydrophilic

• X-ray crystallography combined with computational analysis permits an accurate depiction of the distribution of electrons in covalent bonds and the outermost unbonded electrons of atoms

• These unbonded electrons can form hydrogen bonds with donor hydrogens

Van der Waals Interactions Are Caused by Transient Dipoles

• When any two atoms approach each other closely, they create a weak, nonspecific attractive force called a van der Waals interaction

• These nonspecific interactions result from the momentary random fluctuations in the distribution of the electrons of an atom, which give rise to a transient unequal distribution of electrons

• If two noncovalently bonded atoms are close enough together, electrons of one atom will perturb the electrons of the other

• This perturbation generates a transient dipole in the second atom, and the two dipoles will attract each other weakly

• A polar covalent bond in one molecule will attract an oppositely oriented dipole in another

• Van der Waals interactions, involving either transiently induced or permanent electric dipoles, occur in all types of molecules, both polar and nonpolar

• Particularly, Van der Waals interactions are responsible for the cohesion between molecules of nonpolar liquids and solids, such as heptane [CH3O(CH2)5OCH3] that cannot form hydrogen bonds or ionic interactions with other molecules

• The strength of Van der Waals interactions decreases rapidly with increasing distance; thus these noncovalent bonds can form only when atoms are quite close to one another

• However, if atoms get too close together, they become repelled by the negative charges of their electrons

• When the Van der Waals attraction between two atoms exactly balances the repulsion between their two electron clouds, the atoms are said to be in Van der Waals contact

• The strength of the van der Waals interaction is about 1 kcal/mol, weaker than typical hydrogen bonds and only slightly higher than the average thermal energy of molecules at 25oC

• Thus multiple van der Waals interactions, a Van der Waals interaction in conjunction with other noncovalent interactions, or both are required to significantly influence intermolecular contacts

The Hydrophobic Effect Causes Nonpolar Molecules to Adhere to One Another

• Because nonpolar molecules do not contain charged groups, possess a dipole moment, or become hydrated, they are insoluble or almost insoluble in water; that is, they are hydrophobic

• The covalent bonds between two carbon atoms and between carbon and hydrogen atoms are the most common nonpolar bonds in biological systems

• Hydrocarbons—molecules made up only of carbon and hydrogen—are virtually insoluble in water

• Large triacylglycerols (or triglycerides), which comprise animal fats and vegetable oils, also are insoluble in water

• As we see later, the major portion of these molecules consists of long hydrocarbon chains

• After being shaken in the water, triacylglycerols form a separate phase

• A familiar example is the separation of oil from the water-based vinegar in an oil-and-vinegar salad dressing

• Nonpolar molecules or nonpolar portions of molecules tend to aggregate in water owing to a phenomenon called the hydrophobic effect

• Because water molecules cannot form hydrogen bonds with nonpolar substances, they tend to form “cages” of relatively rigid hydrogen-bonded pentagons and hexagons around nonpolar molecules

• This state is energetically unfavorable because it decreases the randomness (entropy) of the population of water molecules

• If nonpolar molecules in an aqueous environment aggregate with their hydrophobic surfaces facing each other, there is a reduction in the hydrophobic surface area exposed to water

• As a consequence, less water is needed to form the cages surrounding the nonpolar molecules, and entropy increases (an energetically more favorable state) relative to the unaggregated state

• In a sense, then, water squeezes the nonpolar molecules into spontaneously forming aggregates

• Rather than constituting an attractive force such as in hydrogen bonds, the hydrophobic effect results from avoidance of an unstable state (extensive water cages around individual nonpolar molecules)

• Nonpolar molecules can also associate, albeit weakly, through van der Waals interactions

• The net result of the hydrophobic and van der Waals interactions is a very powerful tendency for hydrophobic molecules to interact with one another, not with water. Simply put, like dissolves like

• Polar molecules dissolve in polar solvents such as water; nonpolar molecules dissolve in nonpolar solvents such as hexane

Molecular Complementarity Permits Tight, Highly Specific Binding of Biomolecules

• Inside and outside of cells, ions and molecules are bumping into each other constantly

• When 2 molecules encounter they most likely will bounce apart

• Depending on the number and strength of the non-covalent interactions between 2 molecules and on their environment their binding may be tight/strong or loose/weak

2.2 - Chemical Building Blocks of Cells

• The three most abundant biological macromolecules—proteins, nucleic acids, and polysaccharides—are all polymers composed of multiple covalently linked identical or nearly identical small molecules, or monomers

• Proteins are linear polymers containing ten to several thousand amino acids linked by peptide bonds

• Nucleic acids are linear polymers containing hundreds to millions of nucleotides linked by phosphodiester bonds

• Polysaccharides are linear or branched polymers of monosaccharides (sugars) such as glucose linked by glycosidic bonds

• A similar approach is used to form various large structures in which the repeating components associate with non-covalent interactions

• The repeating theme in biology is the construction of large molecules and structures by the covalent or noncovalent association of many similar or identical smaller molecules

Amino Acids Differing Only in Their Side Chains Compose Proteins

• The monomeric building blocks of proteins are 20 amino acids, all of which have a characteristic structure consisting of a central carbon atom (C) bonded to four different chemical groups: an amino (NH2) group, a carboxyl (COOH) group, hydrogen (H) atom, and one variable group, called a side chain, or R group

• Because the carbon in all amino acids except glycine is asymmetric, these molecules can exist in two mirror-image forms called by convention the D (Dextro) and the L (Levo) isomers

• The two isomers cannot be interconverted (one made identical with the other) without breaking and then re-forming a chemical bond in one of them

• With rare exceptions, only the L forms of amino acids are found in proteins

• The side chains of different amino acids vary in size, shape, charge, hydrophobicity, and reactivity

• Amino acids can be classified into several broad categories based primarily on their solubility in water, which is influenced by the polarity of their side chains

• Amino acids with polar side chains are hydrophilic and tend to be on the surfaces of proteins; by interacting with water, they make proteins soluble in aqueous solutions and can form noncovalent interactions with other water-soluble molecules

• In contrast, amino acids with nonpolar side chains are hydrophobic; they avoid water and often aggregate to help form the water-insoluble cores of many proteins

• The polarity of amino acid side chains thus is responsible for shaping the final three-dimensional structure of proteins

• A subset of the hydrophilic amino acids are charged (ionized) at the pH (≈7) typical of physiological conditions

• Arginine and lysine are positively charged; aspartic acid and glutamic acid are negatively charged (their charged forms are called aspartate and glutamate)

• These four amino acids are the prime contributors to the overall charge of a protein

• The activities of many proteins are modulated by shifts in environmental acidity through the protonation of histidine side chains

• Asparagine and glutamine are uncharged but have polar side chains containing amide groups with extensive hydrogen-bonding capacities

• The side chains of hydrophobic amino acids are insoluble or only slightly soluble in water

• The noncyclic side chains of alanine, valine, leucine, isoleucine, and methionine consist entirely of hydrocarbons, except for the one sulphur atom in methionine, and all are nonpolar

• Phenylalanine, tyrosine, and tryptophan have large bulky aromatic side chains

• Lastly, cysteine, glycine, and proline exhibit special roles in proteins because of the unique properties of their side chains

• The side chain of cysteine contains a reactive sulfhydryl group (OSH), which can oxidize to form a covalent disulphide bond (OSOSO) to a second cysteine

• Regions within a protein chain or in separate chains sometimes are cross-linked through disulphide bonds

• Disulphide bonds are commonly found in extracellular proteins, where they help stabilize the folded structure

• The smallest amino acid, glycine, has a single hydrogen atom as its R group

• Its small size allows it to fit into tight spaces

• The side chain of the proline bends around to form a ring by covalently bonding to the nitrogen atom (amino group) attached to the C

• Proline is very rigid and creates a fixed kink in a protein chain, limiting how a protein can fold in the region of proline residues

• Some amino acids are more abundant in proteins than other amino acids

• Cysteine, tryptophan, and methionine are rare amino acids; together they constitute approximately 5% of the amino acids in a protein

• 4 amino acids are the most abundant amino acids, totaling 32 percent of all the amino acid residues in a typical protein

  • Leucine

  • Serine

  • Lysine

  • Glutamic acid

• However, the amino acid composition of proteins can vary widely from these values

Five Different Nucleotides Are Used to Build Nucleic Acids

• Two types of chemically similar nucleic acids, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are the principal information-carrying molecules of the cell

• The monomers from which DNA and RNA are built, called nucleotides, all have a common structure: a phosphate group linked by a phosphodiester bond to a pentose (a five-carbon sugar molecule) that in turn is linked to nitrogen- and carbon-containing ring structure commonly referred to as a “base”

• In RNA, the pentose is ribose; in DNA, it is deoxyribose

• The bases adenine, guanine, and cytosine are found in both DNA and RNA; thymine is found only in DNA, and uracil is found only in RNA

• Adenine and guanine are purines, which contain a pair of fused rings; cytosine, thymine, and uracil are pyrimidines, which contain a single ring

• The bases are often abbreviated A, G, C, T, and U, respectively; these same single-letter abbreviations are also commonly used to denote the entire nucleotides in nucleic acid polymers

• In nucleotides, the 1 carbon atom of the sugar (ribose or deoxyribose) is attached to the nitrogen at position 9 of a purine (N9) or at position 1 of a pyrimidine (N1)

• The acidic character of nucleotides is due to the phosphate group, which under normal intracellular conditions releases a hydrogen ion (H), leaving the phosphate negatively charged

• Most nucleic acids in cells are associated with proteins, which form ionic interactions with the negatively charged phosphates

• Cells and extracellular fluids in organisms contain small concentrations of nucleosides, combinations of a base and sugar without a phosphate

• Nucleotides are nucleosides that have one, two, or three phosphate groups esterified at the 5 hydroxyl

• Nucleoside monophosphates have a single esterified phosphate, diphosphates contain a pyrophosphate group, triphosphates have the third phosphate

Monosaccharides Joined by Glycosidic Bonds Form Linear and Branched Polysaccharides

• The building blocks of the polysaccharides are the simple sugars or monosaccharides

• Monosaccharides are carbohydrates, which are literally covalently bonded combinations of carbon and water in a one-to-one ratio (CH2O)n, where n equals 3, 4, 5, 6, or 7

• Hexoses (n = 6) and pentoses (n = 5) are the most common monosaccharides

• All monosaccharides contain hydroxyl (OOH) groups and either an aldehyde or a keto group

• D-Glucose (C6H12O6) is the principal external source of energy for most cells in higher organisms and can exist in three different forms: a linear structure and two different

• hemiacetal ring structures

• If the aldehyde group on carbon 1 reacts with the hydroxyl group on carbon 5, the resulting hemiacetal, D-glucopyranose, contains a six-member ring

• Although all three forms of D-glucose exist in biological systems, the pyranose form is by far the most abundant

• Many biologically important sugars are six-carbon sugars that are structurally related to D-glucose

• Mannose is identical with glucose except that the orientation of the groups bonded to carbon 2 is reversed

• Similarly, galactose, another hexose, differs from glucose only in the orientation of the groups attached to carbon 4

• Interconversion of glucose and mannose or galactose requires the breaking and making of covalent bonds; such reactions are carried out by enzymes called epimerases

• The pyranose ring in Figure 2-16a is depicted as planar.

• In fact, because of the tetrahedral geometry around carbon atoms, the most stable conformation of a pyranose ring has a nonplanar, chairlike shape. In this conformation, each bond from a ring carbon to a non-ring atom (e.g., H or O) is either nearly perpendicular to the ring, referred to as axial (a), or nearly in the plane of the ring, referred to as equatorial (e)

• The enzymes that make the glycosidic bonds linking monosaccharides into polysaccharides are specific for the or anomer of one sugar and a particular hydroxyl group on the other

• In principle, any two sugar molecules can be linked in a variety of ways because each monosaccharide has multiple hydroxyl groups that can participate in the formation of glycosidic bonds

• Furthermore, anyone monosaccharide has the potential of being linked to more than two other monosaccharides, thus generating a branch point and nonlinear polymers

• Glycosidic bonds are usually formed between a covalently modified sugar and the growing polymer chain

• Such modifications include a phosphate (e.g., glucose 6-phosphate) or a nucleotide (e.g., UDP-galactose)

• The epimerase enzymes that interconvert different monosaccharides often do so using the nucleotide sugars rather than the unsubstituted sugars

• Disaccharides, formed from two monosaccharides, are the simplest polysaccharides

• Larger polysaccharides, containing dozens to hundreds of monosaccharide units, can function as reservoirs for glucose, as structural components, or as adhesives that help hold cells together in tissues

• The most common storage carbohydrate in animal cells is glycogen, a very long, highly branched polymer of glucose

• As much as 10 percent by weight of the liver can be glycogen

• The primary storage carbohydrate in plant cells, starch, also is a glucose polymer

• It occurs in an unbranched form (amylose) and lightly branched form (amylopectin)

• Both glycogen and starch are composed of the anomer of glucose

• In contrast, cellulose, the major constituent of plant cell walls, is an unbranched polymer of the anomer of glucose

• Human digestive enzymes can hydrolyze the glycosidic bonds in starch, but not the glycosidic bonds in cellulose

• Many species of plants, bacteria, and molds produce cellulose-degrading enzymes

Fatty Acids Are Precursors for Many Cellular Lipids

• Like glucose, fatty acids are an important energy source for many cells and are stored in the form of triacylglycerols within adipose tissue

• Fatty acids also are precursors for phospholipids and many other lipids with a variety of functions

• Fatty acids consist of a hydrocarbon chain attached to a carboxyl group (OCOOH)

• They differ in length, although the predominant fatty acids in cells have an even number of carbon atoms, usually 14, 16, 18, or 20

• Fatty acids often are designated by the abbreviation Cx:y, where x is the number of carbons in the chain and y is the number of double bonds

• Fatty acids containing 12 or more carbon atoms are nearly insoluble in aqueous solutions because of their long hydrophobic hydrocarbon chains

• Fatty acids with no carbon-carbon double bonds are said to be saturated; those with at least one double bond are unsaturated

• Unsaturated fatty acids with more than one carbon-carbon double bond are referred to as polyunsaturated

• Two “essential” polyunsaturated fatty acids, linoleic acid (C18:2) and linolenic acid (C18:3) cannot be synthesized by mammals and must be supplied in their diet

• Mammals can synthesize other common fatty acids

• Two stereoisomeric configurations, cis and trans, are possible around each carbon-carbon double bond

• A cis double bond introduces a rigid kink in the otherwise flexible straight chain of a fatty acid

• In general, the fatty acids in biological systems contain only cis double bonds

• Fatty acids can be covalently attached to another molecule by a type of dehydration reaction called esterification, in which the OH from the carboxyl group of the fatty acid and an H from a hydroxyl group on the other molecule is lost

• In the combined molecule formed by this reaction, the portion derived from the fatty acid is called an acyl group, or fatty acyl group

Phospholipids Associate Noncovalently to Form the Basic Bilayer Structure of Biomembranes

• Biomembranes are large flexible sheets that serve as the boundaries of cells and their intracellular organelles and form the outer surfaces of some viruses

• Membranes literally define what is a cell (the outer membrane and the contents within the membrane) and what is not (the extracellular space outside the membrane)

• Unlike the proteins, nucleic acids, and polysaccharides, membranes are assembled by the noncovalent association of their component building blocks

• The primary building blocks of all biomembranes are phospholipids, whose physical properties are responsible for the formation of the sheetlike structure of membranes

• Phospholipids consist of two long-chain, nonpolar fatty acyl groups linked (usually by an ester bond) to small, highly polar groups, including a phosphate

• In phosphoglycerides, the major class of phospholipids, fatty acyl side chains are esterified to two of the three hydroxyl groups in glycerol

• The third hydroxyl group is esterified to phosphate

• The simplest phospholipid, phosphatidic acid, contains only these components

• In most phospholipids found in membranes, the phosphate group is esterified to a hydroxyl group on another hydrophilic compound

• The negative charge on the phosphate as well as the charged or polar groups esterified to it can interact strongly with water

• The phosphate and its associated esterified group, the “head” group of a phospholipid, is hydrophilic, whereas the fatty acyl chains, the “tails,” are hydrophobic

• The amphipathic nature of phospholipids, which governs their interactions, is critical to the structure of biomembranes

• When a suspension of phospholipids is mechanically dispersed in an aqueous solution, the phospholipids aggregate into one of three forms: spherical micelles and liposomes and sheetlike, two-molecule-thick phospholipid bilayers

• The type of structure formed by a pure phospholipid or a mixture of phospholipids depends on several factors, including the length of the fatty acyl chains, their degree of saturation, and temperature. In all three structures, the hydrophobic effect causes the fatty acyl chains to aggregate and exclude water molecules from the “core.”

• Micelles are rarely formed from natural phosphoglycerides, whose fatty acyl chains generally are too bulky to fit into the interior of a micelle

• If one of the two fatty acyl chains is removed by hydrolysis, forming a lysophospholipid, the predominant type of aggregate that forms is the micelle

• Common detergents and soaps form micelles in an aqueous solution that behave as tiny ball bearings, thus giving soap solutions their slippery feel and lubricating properties

• Under suitable conditions, phospholipids of the components present in cells spontaneously form symmetric phospholipid bilayers

• Each phospholipid layer in this lamellar structure is called a leaflet

• The fatty acyl chains in each leaflet minimize contact with water by aligning themselves

  • Tightly together in the center of the bilayer, forming a hydrophobic core that is about 3 nm thick

• The close packing of these nonpolar tails is stabilized by the hydrophobic effect and Van der Waals interactions between them

• Ionic and hydrogen bonds stabilize the interaction of the phospholipid polar head groups with one another and with water.

• A phospholipid bilayer can be of almost unlimited size—from micrometers (m) to millimeters (mm) in length or width—and can contain tens of millions of phospholipid molecules

• Because of their hydrophobic core, bilayers are virtually impermeable to salts, sugars, and most other small hydrophilic molecules

• The phospholipid bilayer is the basic structural unit of nearly all biological membranes; thus, although they contain other molecules (e.g., cholesterol, glycolipids, proteins)

  • Biomembranes have a hydrophobic core that separates two aqueous solutions and acts as a permeability barrier

2.3 - Chemical Equilibrium

Equilibrium Constants Reflect the Extent of a Chemical Reaction

• The equilibrium constant Keq depends on the nature of the reactants and products, the temperature, and the pressure (particularly in reactions involving gases)

• Under standard physical conditions (25oC and 1 atm pressure, for biological systems), the Keq is always the same for a given reaction, whether or not a catalyst is present

Chemical Reactions in Cells Are at Steady State

• Under appropriate conditions and given sufficient time, individual biochemical reactions carried out in a test tube eventually will reach equilibrium

• Within cells, however, many reactions are linked in pathways in which a product of one reaction serves as a reactant in another or is pumped out of the cell

• In this more complex situation, when the rate of formation of a substance is equal to the rate of its consumption, the concentration of the substance remains constant

  • The system of linked reactions for producing and consuming that substance is said to be in a steady-state

• One consequence of such linked reactions is that they prevent the accumulation of excess intermediates, protecting cells from the harmful effects of intermediates that have the potential of being toxic at high concentrations

Dissociation Constants for Binding Reactions Reflect the Affinity of Interacting Molecules

• Many important cellular processes depend on such binding “reactions,” which involve the making and breaking of various noncovalent interactions rather than covalent bonds

• A common example is the binding of a ligand (e.g., the hormone insulin or adrenaline) to its receptor on the surface of a cell, triggering a biological response

• If the equilibrium constant for a binding reaction is known, the intracellular stability of the resulting complex can be predicted

• Most commonly, binding reactions are described in terms of the dissociation constant Kd, which is the reciprocal of the equilibrium constant

• Binding reaction P+D=PD, where PD is the specific complex of protein (P) and DNA (D) the dissociation, is constant is given by

  • P and D bind very tightly (have a high affinity)

• The large size of biological macromolecules (such as proteins), can result in the availability of multiple surfaces for complementary intermolecular interactions

• Many macromolecules have the capacity to bind multiple other molecules simultaneously

• Sometimes these binding reactions are independent, with their own distinct Kd values that are constant