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Textbook: Biology, 8th Edition, Campbell & Reece. Websites: www.pubmed.gov www.who.int/en/ www.cdc.gov www.cdc.gov/mmwr/

Basic Biochemical Molecules

Matter consists of chemical elements in pure form and in

combinations called compounds

Organisms are composed of matter. Matter is anything that takes up space and has mass. An element is a substance that cannot be broken down to other substances by chemical reactions. There are 92 naturally-occurring elements. Each element has a unique symbol, usually from the first one or two letters of the name, often from Latin or German.

 A compound is a substance consisting of two or more elements in a fixed ratio.

Table salt (sodium chloride or NaCl) is a compound with equal numbers of chlorine and sodium atoms. While pure sodium is a metal and chlorine is a gas, their combination forms an edible compound, an emergent property.

Fig. 2.3
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The Essential Elements

About 25 of the 92 natural elements are known to be essential for life.
Four elements - carbon (C), oxygen (O), hydrogen (H), and nitrogen (N) - make up 96% of living matter. Most of the remaining 4% of an organisms weight consists of phosphorus (P), sulphur (S), calcium (Ca), and potassium (K).

 Trace elements are required by an organism but only in minute quantities.

Some trace elements, like iron (Fe), are required by all organisms. Other trace elements are required only by some species.
For example, a daily intake of 0.15 milligrams of iodine is required for normal activity of the human thyroid gland.

Fig. 2.4

Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Atoms & Molecules

Each element consists of unique atoms. An atom is the smallest unit of matter that still retains the properties of an element.
Atoms are composed of even smaller parts, called subatomic particles. Two of these, neutrons and protons, are packed together to form a dense core, the atomic nucleus, at the center of an atom. Electrons form a cloud around the nucleus.

 Each electron has one unit of negative charge. Each proton has one unit of positive charge. Neutrons are electrically neutral. The attractions between the positive charges in the nucleus and the negative charges of the electrons keep the electrons in the vicinity of the nucleus.

Fig. 2.5
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 A neutron and a proton are almost identical in mass, about 1.7 x 10-24 gram per particle. The dalton, is used to measure the mass subatomic particles, atoms or molecules.
The mass of a neutron or a proton is close to 1 dalton.

The mass of an electron is about 1/2000th that of a neutron or proton.

the contribution of electrons when determining the total mass of an atom is usually ignored.

 Atoms of a particular element have the same number of protons in their nuclei.
Each element has a unique number of protons, the atomic number.

Unless otherwise indicated, atoms have equal numbers of protons and electrons - no net charge.
the atomic number is the number of protons and the number of electrons that are found in a neutral atom of a specific element.

 The mass number is the sum of the number of protons and neutrons in the nucleus of an atom.
the number of neutrons in an atom = the mass number - the number of protons (the atomic number).

The atomic weight of an atom, a measure of its mass, can be approximated by the mass number.
For example, He has a mass number of 4 and an estimated atomic weight of 4 daltons. More precisely, its atomic weight is 4.003 daltons.

 Atoms of a given element have the same number of protons, but they may differ in the number of neutrons. Isotopes = two atoms of the same element that differ in the number of neutrons. In nature, an element occurs as a mixture of isotopes.
For example, 99% of carbon atoms have 6 neutrons (12C). Most of the remaining 1% of carbon atoms have 7 neutrons (13C) while the rarest isotope, with 8 neutrons is 14C.

 Most isotopes are stable; they do not tend to loose particles.

Both 12C and 13C are stable isotopes.

The nuclei of some isotopes are unstable and decay spontaneously, emitting particles and energy.
14C is an unstable or radioactive isotopes. In its decay, an neutron is converted to a proton and electron. This converts 14C to 14N, changing the identity of that atom.

Interaction of Elements
When two elements interact during a chemical reaction, it is actually their electrons that are actually involved. The nuclei do not come close enough to interact The electrons of an atom may vary in the amount of energy that they possess Electrons have potential (stored) energy because of their position relative to the nucleus. The negatively charged electrons are attracted to the positively charged nucleus. The farther electrons are from the nucleus, the more potential energy they have.

Energy Levels
The different states of potential energy that the electrons of an atoms can have are called energy levels or electron shells.
The first shell, closest to the nucleus, has the lowest potential energy. Electrons in outer shells have more potential energy. Electrons can only change their position if they absorb or release a quantity of energy that matches the difference in potential energy between the two levels.

Fig. 2.8
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 The chemical behavior of an atom is determined by its electron configuration electron configuration = the distribution of electrons in its electron shells.
The first 18 elements can be arranged in 8 columns and 3 rows.
Elements in the same row use the same shells. Moving from left to right, each element has a sequential addition of electrons (and protons).

Hydrogen 1H Atomic mass First shell

2 He 4.00

Atomic number
Element symbol

Helium 2He

Electron-shell diagram

Lithium 3Li Second shell

Beryllium 4Be

Boron 3B

Carbon 6C

Nitrogen 7N

Oxygen 8O

Fluorine 9F

Neon 10Ne

Sodium Magnesium Aluminum 13Al 11Na 12Mg Third shell

Silicon 14Si

Phosphorus 15P

Sulfur 16S

Chlorine 17Cl

Argon 18Ar

Fig. 2.9

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Electron Orbitals
An electron occupies a three-dimensional space, an orbital.
The first shell contains a single spherical orbital for its pair of electrons. The second shell can contain pairs of electrons into a spherical orbital and three p orbitals (dumbbell-shaped).

Fig. 2.10 Electron Orbitals

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Chemical Bonds
Atoms interact by either sharing or transferring electrons. Atoms remain close together, held by chemical bonds.
The strongest chemical bonds are covalent bonds and ionic bonds.

 A covalent bond is the sharing of a pair of valence (outermost) electrons by two atoms.
If two atoms come close enough that their unshared orbitals overlap, each atom can count both electrons toward its goal of filling the valence shell. For example, if two hydrogen atoms come close enough that their 1s orbitals overlap, then they can share the single electrons that each contributes.

 Formation of a covalent bond

Hydrogen atoms (2 H)

In each hydrogen atom, the single electron is held in its orbital by its attraction to the proton in the nucleus.

When two hydrogen atoms approach each other, the electron of each atom is also attracted to the proton in the other nucleus.

The two electrons become shared in a covalent bond, forming an H2 molecule.

Hydrogen molecule (H2)

Figure 2.11

 A molecule
Consists of two or more atoms held together by covalent bonds

A single bond
Is the sharing of one pair of valence electrons

A double bond
Is the sharing of two pairs of valence electrons

 Single and double covalent bonds

Name (molecular formula) Electronshell diagram Structural formula Spacefilling model

(a) Hydrogen (H2). Two hydrogen atoms can form a single bond.

(b) Oxygen (O2). Two oxygen atoms share two pairs of electrons to form a double bond.

Figure 2.12

 Covalent bonding in compounds

Name (molecular formula) Electronshell diagram Structural formula Spacefilling model

(c) Water (H2O). Two hydrogen atoms and one oxygen atom are joined by covalent bonds to produce a molecule of water.

O H

(d) Methane (CH4). Four hydrogen atoms can satisfy the valence of one carbon atom, forming methane.

H H C H H

Figure 2.12

 Molecule = Two or more atoms held together by covalent bonds.

Structural formula - substitute a line for each pair of shared electrons, H-H = the structural formula for the covalent bond between two hydrogen atoms. The molecular formula indicates the number and types of atoms present in a single molecule.
H2 is the molecular formula for hydrogen gas.

 Covalent bonds can form between atoms of the same element or atoms of different elements to form a compound.
Water, H2O, is a compound in which two hydrogen atoms form single covalent bonds with an oxygen atom.

Fig. 2.12
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 Electronegativity = the attraction of an atom for the electrons of a covalent bond.

Strongly electronegative atoms attempt to pull the shared electrons toward themselves.

Nonpolar covalent bond = electrons in a covalent bond that are shared equally.
A covalent bond between two atoms of the same element is always nonpolar. A covalent bond between atoms that have similar electronegativities is also nonpolar.
Because carbon and hydrogen do not differ greatly in electronegativities, the bonds of CH4 are nonpolar.

 Polar covalent bond = electrons in a covalent bond are not shared equally by the two atoms,.
The bonds between oxygen and hydrogen in water are polar covalent because oxygen has a much higher electronegativity than does hydrogen. Compounds with a polar covalent bond have regions that have a partial negative charge near the strongly electronegative atom and a partial positive charge near the weakly electronegative Fig. 2.13 atom.
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 Ionic bond = two atoms are so unequal in their attraction for valence electrons that one atom strips an electron completely from the other.
For example, sodium with one valence electron in its third shell transfers this electron to chlorine with 7 valence electrons in its third shell. Now, sodium has a full valence shell (the second) and chlorine has a full valence shell (the third).

Fig. 2.14
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 After an electron transfer, atoms are no longer neutral, but are charged and are called ions. Sodium has one more proton than electrons and has a net positive charge.
Atoms with positive charges are cations.

Chlorine has one more electron than protons and has a net negative charge.
Atoms with negative charges are anions.

Fig. 2.14
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 Cations and anions are attracted to each other to form an ionic bond.
This attraction is due to charge differences

Importance of Weak Bonds

Weak chemical bonds between molecules are important to a number of processes.
signal molecules from one neuron use weak bonds to bind briefly to receptor molecules on the surface of a receiving neuron. This triggers a momentary response by the recipient.

Weak interactions = ionic bonds (weak in water), hydrogen bonds, and van der Waals forces.
Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Hydrogen (H) bonds A H bond is formed when a hydrogen atom covalently bound to a strongly electronegative atom is attracted to another strongly electronegative atom.
The electronegative atoms are usually nitrogen or oxygen The H bond joins H in water with N in ammonia
Fig. 2.16

 Molecules with nonpolar covalent bonds can have partially negative and positive regions.
Because electrons are constantly in motion, there can be periods when they accumulate randomly in one area of a molecule. This creates random regions of negative and positive charge within a molecule.

Molecules or atoms in close proximity can be attracted by these charge differences, creating van der Waals forces/interactions.

Chemical Reactions
In chemical reactions chemical bonds are broken and reformed, leading to new arrangements of atoms. reactants products In a chemical reaction, all of the atoms in the reactants must be accounted for in the products.

Formation of Water H2 + O2 = H2O. Two molecules of H2 combine with one molecule of O2 to form two molecules of H2O.

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 Some chemical reactions go to completion; that is, all the reactants are converted to products. A+B C Most chemical reactions are reversible, the products in the forward reaction becoming the reactants for the reverse reaction. A+B AB

Equilibrium The rate of formation of products will equal the rate of breakdown of products, thus the system approaches a chemical equilibrium.
At equilibrium, products and reactants are continually being formed There is no net change in the concentrations of reactants and products.

Water
Solution = a liquid that is a completely homogeneous mixture of two or more substances. A sugar cube in a glass of water will eventually dissolve to form a uniform mixture of sugar and water. Solvent = the dissolving agent Solute = substance that is dissolved for example, water is the solvent and sugar the solute. In an aqueous solution, water is the solvent. Water is not a universal solvent, however, it is versatile because of the polarity of water molecules.

Water
Water is an effective solvent as it readily forms hydrogen bonds with charged and polar covalent molecules.
A substance that has an affinity for water is hydrophilic. A substance that has no affinity for water is hydrophobic.

Macromolecules
Cells join smaller organic molecules together to form macromolecules. Macromolecules are composed of thousands of atoms and weigh over 100,000 daltons. 4 major classes of macromolecules: carbohydrates, lipids, proteins, and nucleic acids.

Polymers
Three of the four classes of macromolecules form molecules called polymers. Polymers consist of many similar or identical units linked by covalent bonds. The repeated units are small molecules called monomers.

1. Carbohydrates
Carbohydrates include sugars and polymers. The simplest carbohydrates are monosaccharides or simple sugars. Disaccharides consist of two monosaccharides. Polysaccharides are polymers of monosaccharides.

Function of Carbohydrates
Monosaccharides (sugars), the smallest carbohydrates = source of fuel and carbon sources e.g. glucose Polysaccharides = energy storage macromolecules that are hydrolyzed as needed e.g. starch
Polysaccharides = building materials for the cell or organism e.g. cellulose, chitin

2. Lipids
3 important families: Fats, phospholipids, steroids Lipids are an exception among macromolecules, they do not have polymers. Lipids have little or no affinity for water.
This is because their structures are dominated by nonpolar covalent bonds. Are lipids hydrophilic or hydrophobic?

Lipids are diverse in structure and function.

Fats
Fats are not polymers but they are large molecules assembled from smaller molecules. A fat is made from 1 glycerol and 3 fatty acids.

Glycerol consists of a three carbon skeleton with a hydroxyl group attached to each. A fatty acid consists of a carboxyl group attached to a long carbon skeleton, often 16 to 18 carbons long.

Fat & Fatty Acids

The three fatty acids in a fat can be the same or different. Fatty acids vary in the number of carbons and in the number and locations of double bonds.
saturated fatty acid = no carbon-carbon double bonds unsaturated fatty acid = one or more carboncarbon double bonds

Saturated & Unsaturated Fats

Fats with saturated fatty acids are saturated fats.
Most animal fats are saturated. Saturated fat are solid at room temperature. A diet rich in saturated fats may contribute to cardiovascular disease (atherosclerosis) through plaque deposits.

Fats with unsaturated fatty acids are unsaturated fats.

Plant and fish fats, known as oils, are liquid are room temperature.

Function of Fats
The major function of fat is energy storage.
A gram of fat stores more than twice as much energy as a gram of a polysaccharide. Plants use starch for energy storage when mobility is not a concern but use oils when dispersal and packing is important, as in seeds. Humans and other mammals store fats as longterm energy reserves in adipose cells. Fat functions to cushion vital organs. A layer of fat can function as insulation. This subcutaneous layer is especially thick in whales, seals, and most other marine mammals.

Phospholipids
Phospholipids = two fatty acids attached to glycerol and a phosphate group at the third position. Phospholipids + water: they self-assemble into aggregates, the hydrophobic tails point inward and the hydrophilic heads point outward.
This structure is called a micelle.

 At the surface of a cell phospholipids are arranged as a bilayer.

Again, the hydrophilic heads are on the outside in contact with the aqueous solution and the hydrophobic tails from the core. The phospholipid bilayer forms a barrier between the cell and the external environment.

They are the major component of membranes.

See Fig. 5.13

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Steroids
Steroids are lipids with a carbon skeleton consisting of four fused carbon rings. Cholesterol, an important steroid, is a component in animal cell membranes. Cholesterol is also the precursor from which all other steroids are synthesized. Many of these other steroids are hormones, including the vertebrate sex hormones. While cholesterol is clearly an essential molecule, high levels of cholesterol in the blood may contribute to cardiovascular disease.

3. Proteins
Proteins are structurally complex molecules. Each type of protein has a complex threedimensional shape or conformation.

All protein polymers are constructed from the same set of 20 monomers, called amino acids. Polymers of proteins are called polypeptides. A protein consists of one or more polypeptides folded and coiled into a specific conformation.

Proteins
Protein functions include structural support, storage, transport of other substances, intercellular signaling, movement, and defense against foreign substances.

Humans have 1000s of different proteins, each with their own structure and function

Protein Form & Function

A functional proteins consists of one or more polypeptides that have been precisely folded, into a unique structure. It is the order of amino acids that determines what the three-dimensional conformation will be. A proteins specific conformation determines its function. Protein function usually depends on its ability to recognize and bind to some other molecule.

4. Nucleic Acids
There are 2 types of nucleic acid, deoxyribonucleic acid and ribonucleic acid (DNA and RNA) The amino acid sequence of a polypeptide is programmed by a gene. A gene consists of regions of DNA, a polymer of nucleic acids. DNA (and their genes) is passed by the mechanisms of inheritance.

 The flow of genetic information is from DNA -> RNA -> protein.
Protein synthesis occurs in cellular structures called ribosomes. In eukaryotes, DNA is located in the nucleus, but most ribosomes are in the cytoplasm with mRNA as an intermediary.

Fig. 5.26
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First, some definitions.

Genome
All the genes in a cell or virus

Gene
A linear sequence of nucleotides with definite end and start points

DNA Building Blocks

Nucleotides
A nucleoside with one or more phosphate groups attached

Nucleosides
A purine or pyrimidine base joined to either ribose or deoxyribose

Purine & Pyrimidine

Cyclic nitrogenous structures:
purines have 2 rings, adenine and guanine pyrimidines have 1 ring, cytosine, thymine (DNA) and uracil (RNA)

Composition of Nucleic Acids

DNA Structure
2 polynucleotide chains coiled together to form a double helix, 2.0 nm in diameter Each chain is comprised of purine and pyrimidine deoxyribonucleosides (bases) joined by phosphodiesterase bridges The bases are stacked on top of each other & paired specifically A--T, C---G (- = H bonds) = base pairing Base pairing enables 2 stands of DNA in the helix to be complementary

 The sugar-phosphate backbones of the two polynucleotides are on the outside of the helix.
Pairs of nitrogenous bases, one from each strand, connect the polynucleotide chains with hydrogen bonds. Most DNA molecules have thousands to millions of base pairs.
Fig. 5.28
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Base Pairing
Adenine (A) always pairs with thymine (T) Guanine (G) always pairs with cytosine (C). With base-pairing rules, the sequence of bases on one strand is the mirror image of the sequence on the opposite strand. The two strands are complementary.

Function of Nucleic Acids

Storage of genetic information We will come back to DNA in more detail later in the course.

Metabolism
Metabolism = the totality of an organisms chemical reactions. Metabolic pathways change molecules in a stepwise fashion. Enzymes selectively accelerate each step. The action of enzymes is regulated to allow the correct amount of each pathway product to be produced/degraded. Bioenergetics is the study of how organisms manage their energy resources.

Metabolism = Catabolism + Anabolism

Catabolic pathways release energy by breaking down complex molecules to simpler compounds. This energy is stored in organic molecules. Anabolic pathways consume energy to build complicated molecules from simpler compounds. The energy released by catabolic pathways is used to drive anabolic pathways.

Energy
Energy = the capacity to do work - to move matter against opposing forces. Kinetic energy = the energy of motion. e.g. objects in motion, photons, and heat Potential energy = the energy that matter possesses because of its location or structure. Chemical energy is a form of potential energy in molecules because of the arrangement of atoms. Free Energy = portion of a systems energy that is available for work

Thermodynamics is the study of energy transformations.

In thermodynamics, system indicates the matter under study and the surroundings are everything outside the system. A closed system, like liquid in a thermos, is isolated from its surroundings. In an open system energy (and often matter) can be transferred between the system and surroundings. Organisms are open systems. They absorb light or chemical energy and release heat and metabolic waste products.

Two Laws of Thermodynamics

The first law of thermodynamics: energy can be transferred and transformed, but it cannot be created or destroyed.
Plants transform light to chemical energy; they do not produce energy.

The second law of thermodynamics: every energy transformation must make the universe more disordered.
Entropy is a quantity used as a measure of disorder, or randomness.

Enzymes
A catalyst is a chemical agent that changes the rate of a reaction without being consumed by the reaction.
An enzyme is a catalytic protein.

Enzymes regulate the movement of molecules through metabolic pathways.

 Activation energy is the amount of energy necessary to push the reactants over an energy barrier.
At the summit the molecules are at an unstable point, the transition state. The difference between free energy of the products and the free energy of the reactants is the delta G.

Fig. 8.14

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 Enzyme speed reactions by lowering EA.

The transition state can then be reached even at moderate temperatures.

Enzymes do not change delta G.

It hastens reactions that would occur eventually. Because enzymes are so selective, they determine which chemical processes will occur at any time.
Fig. 8.15
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Substrates & Enzymes

A substrate is a reactant which binds to an enzyme.
When a substrate or substrates binds to an enzyme, the enzyme catalyzes the conversion of the substrate to the product.

Enzymes are unaffected by reactions and are reusable.

 The active site of an enzymes is a pocket or groove on the surface of the protein into which the substrate fits. The specificity of an enzyme is due to the fit between the active site and that of the substrate. As the substrate binds, the enzyme changes shape leading to a tighter induced fit, bringing chemical groups in position to catalyze the reaction.

Fig. 8.16
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 The catalytic cycle of an enzyme

1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds.

Substrates

Enzyme-substrate complex

6 Active site Is available for two new substrate Mole. Enzyme

3 Active site (and R groups of its amino acids) can lower EA and speed up a reaction by acting as a template for substrate orientation, stressing the substrates and stabilizing the transition state, providing a favorable microenvironment, participating directly in the catalytic reaction.

5 Products are Released.

Figure 8.17

Products

4 Substrates are Converted into Products.

 How do Enzymes operate?

The active site orients substrates in the correct orientation for the reaction. As the active site binds the substrate, it may put stress on bonds that must be broken, making it easier to reach the transition state. R groups at the active site may create a conducive microenvironment for a specific reaction. Enzymes may even bind covalently to substrates in an intermediate step before returning to normal.

Concentration Dependence: At low substrate concentrations, an increase in substrate increases binding to available active sites. This does not happen at high concentrations. At some substrate concentrations, the active sites on all enzymes are full, called enzyme saturation. The only way to increase productivity at this point is to provide more active sites.
How can we provide more active sites?

Factors affecting Enzyme Activity

The structures of enzymes depend on environmental conditions. Changes in shape influence the reaction rate. pH Temperature Co-factors