Chapter 2 Summary PDF

2 Molecular Interactions Science regards man as an aggregation of atoms temporarily Dicer enzyme that...

2 Molecular Interactions Science regards man as an aggregation of atoms temporarily Dicer enzyme that makes siRNA united by a mysterious force called the life-principle. H. P. Blavatsky, 1877. In Isis Unveiled: A Master-Key to the Mysteries of Ancient and Modern Science and Theology, Vol. I: Science 2.1 Molecules and Bonds 29 2.2 Noncovalent Interactions 40 2.3 Protein Interactions 46 LO 2.1.1 Compare and contrast the composi- LO 2.2.1 on ras he s ruc ure and so u i i y LO 2.3.1 is se en i por an unc ions o tion, structure, and functions of the four of polar and nonpolar molecules. so u e pro eins in he ody. major groups of biomolecules. LO 2.2.2 escri e he co a en and nonco a- LO 2.3.2 p ain he eanings o a ini y speci- LO 2.1.2 Describe four important biological lent interactions that contribute to molecu- ici y sa ura ion and co pe i ion in pro ein roles of electrons. lar shape, and explain how molecular shape ligand binding. LO 2.1.3 Describe and compare the differ- is related to molecular function. LO 2.3.3 p ain he di eren e hods y en ypes o co a en and nonco a en LO 2.2.3 Define pH in words and mathemati- which modulators alter protein binding or bonds. ca y and e p ain he di erences e ween pro ein ac i i y. acids, bases, and buffers.  2.1 Molecules and Bonds 29 early 100 years ago two scientists, Aleksander Oparin in it pertains to physiology. You can test your knowledge of basic N Russia and John Haldane in England, speculated on how chemistry and biochemistry with a special review quiz at the end CHAPTER life might have arisen on a primitive Earth whose atmo- of the chapter. sphere consisted mainly of hydrogen, water, ammonia, and methane. Their theories were put to the test in 1953, when a 23-year-old scientist named Stanley Miller combined these 2.1 Molecules and Bonds 2 molecules in a closed flask and boiled them for a week while There are more than 100 known elements on Earth, but only periodically discharging flashes of electricity through them, three—oxygen, carbon, and hydrogen—make up more than 90% simulating lightning. At the end of his test, Miller found amino of the body’s mass. These three plus eight additional elements acids had formed in the flask. With this simple experiment, he are considered major essential elements. Some additional minor essential had shown that it was possible to create organic molecules, usu- elements (trace elements) are required in minute amounts, but there ally associated with living creatures, from nonliving inorganic is no universal agreement on which trace elements are essential for precursors. cell function in humans. A periodic table showing the major and Miller’s experiments were an early attempt to solve one of commonly accepted minor essential elements is located inside the the biggest mysteries of biology: How did a collection of chemi- back cover of the book. cals first acquire the complex properties that we associate with living creatures? We still do not have an answer to this question. Numerous scientific theories have been proposed, ranging from Most Biomolecules Contain Carbon, Hydrogen, life arriving by meteor from outer space to molecules forming in and Oxygen deep ocean hydrothermal vents. No matter what their origin, the Molecules that contain carbon are known as organic molecules, molecules associated with living organisms have the ability to orga- because it was once thought that they all existed in or were derived nize themselves into compartments, replicate themselves, and act from plants and animals. Organic molecules associated with liv- as catalysts to speed up reactions that would otherwise proceed too ing organisms are also called biomolecules. There are four slowly to be useful. major groups of biomolecules: carbohydrates, lipids, proteins, and The human body is far removed from the earliest life forms, nucleotides. but we are still a collection of chemicals—dilute solutions of dis- The body uses carbohydrates, lipids, and proteins for energy solved and suspended molecules enclosed in compartments with and as the building blocks of cellular components. The fourth lipid-protein walls. Strong links between atoms, known as chemi- group, the nucleotides, includes DNA, RNA, ATP, and cyclic AMP. cal bonds, store and transfer energy to support life functions. DNA and RNA are the structural components of genetic material. Weaker interactions between and within molecules create distinc- ATP (adenosine triphosphate) and related molecules carry energy, tive molecular shapes and allow biological molecules to interact while cyclic AMP (adenosine monophosphate; cAMP) and related reversibly with each other. compounds regulate metabolism. This chapter introduces some of the fundamental principles Each group of biomolecules has a characteristic composition of molecular interactions that you will encounter repeatedly in and molecular structure. Lipids are mostly carbon and hydrogen your study of physiology. The human body is more than 50% (FIG. 2.1). Carbohydrates are primarily carbon, hydrogen, and water, and because most of its molecules are dissolved in this water, oxygen, in the ratio CH2O (FIG. 2.2). Proteins and nucleotides we will review the properties of aqueous solutions. If you would contain nitrogen in addition to carbon, hydrogen, and oxygen like to refresh your understanding of the key features of atoms, (FIGS. 2.3 and 2.4). Two amino acids, the building blocks of chemical bonds, and biomolecules, you will find a series of one- proteins, also contain sulfur. and two-page review features that encapsulate biochemistry as Not all biomolecules are pure protein, pure carbohydrate, or pure lipid, however. Conjugated proteins are protein molecules combined with another kind of biomolecule. For example, proteins combine with lipids to form lipoproteins. Lipoproteins are found RUNNING PROBLEM Chromium Supplements in cell membranes and in the blood, where they act as carriers for “Lose weight while gaining muscle,” the ads promise. “Prevent less soluble molecules, such as cholesterol. heart disease.” “Stabilize blood sugar.” What is this miracle sub- Glycosylated molecules are molecules to which a carbohydrate stance? It’s chromium picolinate, a nutritional supplement being has been attached. Proteins combined with carbohydrates marketed to consumers looking for a quick fix. Does it work, form glycoproteins. Lipids bound to carbohydrates become though, and is it safe? Some athletes, like Stan—the star run- glycolipids. Glycoproteins and glycolipids, like lipoproteins, are ning back on the college football team—swear by it. Stan takes important components of cell membranes (see Chapter 3). 500 micrograms of chromium picolinate daily. Many researchers, Many biomolecules are polymers, large molecules made however, are skeptical and feel that the necessity for and safety up of repeating units {poly-, many + -mer, a part}. For example, of chromium supplements have not been established. glycogen and starch are both glucose polymers. They differ in the way the glucose molecules attach to each other, as you can see at 29 39 40 41 46 48 53 the bottom of Figure 2.2. FIG. 2.1 REVIEW Biochemistry of Lipids Lipids are biomolecules made mostly of carbon and hydrogen. Most lipids have a backbone of glycerol and 1–3 fatty acids. An important characteristic of lipids is that they are nonpolar and therefore not very soluble in water. Lipids can be divided into two broad categories. Fats are solid at room temperature. Most fats are derived from animal sources. Oils are liquid at room temperature. Most plant lipids are oils. Fatty Acids Formation of Lipids Fatty acids are long chains of carbon atoms bound to hydrogens, with CH2OH Glycerol is a simple 3-carbon molecule a carboxyl (–COOH) or “acid” group at one end of the chain. that makes up the backbone of most HO CH lipids. Palmitic acid, a saturated fatty acid H CH2OH Glycerol + Fatty acid H H H H H H H H H H H H H O H3C C C C C C C C C C C C C C C C Glycerol plus one OH fatty acid produces Monoglyceride H H H H H H H H H H H H H H a monoglyceride. Y Saturated fatty acids have no double bonds between carbons, so they are “saturated” with hydrogens. The more saturated a fatty acid is, the more likely it is to be solid at room temperature. Fatty acid Oleic acid, a monounsaturated fatty acid H H H H H H H H H H H H H H H H Glycerol plus two O fatty acids produces Diglyceride H3C C C C C C C C C C C C C C C C C C Fatty acid a diglyceride. OH Y H H H H H H H H H H H H H H Monounsaturated fatty acids have one double bond between two of the carbons in the chain. For each double bond, the molecule has two Fatty acid fewer hydrogen atoms attached to the carbon chain. Linolenic acid, a polyunsaturated fatty acid Glycerol plus three Triglyceride H H H H H H H H H H H H H H H H fatty acids produces O Fatty acid a triglyceride H3C C C C C C C C C C C C C C C C C C Y OH (triacylglycerol). Fatty acid H H H H H H H H H H More than 90% of lipids are in the form Fatty acid Polyunsaturated fatty acids have two or more double bonds between of triglycerides. carbons in the chain. Lipid-Related Molecules In addition to true lipids, this category includes three types of lipid-related molecules. Eicosanoids Steroids Phospholipids Eicosanoids {eikosi, twenty} are Steroids are lipid- Phospholipids have 2 fatty acids CH3 H modified 20-carbon fatty acids with a related molecules and a phosphate group (–H2PO4). complete or partial carbon ring at one whose structure H C CH2 CH2 CH2 C CH3 Cholesterol and phospholipids are end and two long carbon chain “tails.” includes four H3C important components of animal linked carbon CH3 cell membranes. O rings. H3C COOH Cholesterol is the primary source of steroids in the human body. Fatty acid Y OH HO OH CH2OH Prostaglandin E2 (PGE2) Fatty acid C O P Eicosanoids, such as thromboxanes, H3C HO OH leukotrienes, and prostaglandins, act as H3C Phosphate regulators of physiological functions. group Cortisol O  FIG. 2.2 REVIEW Biochemistry of Carbohydrates Carbohydrates are the most abundant biomolecule. They get their name from their structure, literally carbon {carbo-} with water {hydro-}. The general formula for a carbohy- drate is (CH2O)n or CnH2nOn, showing that for each carbon there are two hydrogens and one oxygen. Carbohydrates can be divided into three categories: monosaccharides, disaccharides, and complex glucose polymers called polysaccharides. Monosaccharides Monosaccharides are simple sugars. The most common monosaccharides are the building blocks of complex carbohydrates and have either five carbons, like ribose, or six carbons, like glucose. Five-Carbon Sugars (Pentoses) Six-Carbon Sugars (Hexoses) Ribose Deoxyribose Fructose Glucose (dextrose) Galactose H HOCH2 H–C–OH HOCH2 O OH HOCH2 O OH HOCH2 O OH HO O H C O H HO C H C OH OH H CH2OH HO HO OH C C OH OH OH OH OH Notice that the H OH C5H10O5 C5H10O4 only difference between glucose and galactose is the spatial Forms the sugar- Forms the sugar- arrangement of phosphate phosphate backbone the hydroxyl (–OH) backbone of RNA of DNA groups. Disaccharides Disaccharides consist of glucose plus another monosaccharide. Sucrose (table sugar) Maltose Lactose Glucose* + Fructose Glucose + Glucose Galactose + Glucose HOCH2 HOCH2 HOCH2 HOCH2 HOCH2 *In shorthand chemical notation, O O HOCH2 O O HO O O the carbons in the rings and their associated hydrogen atoms are O O O OH HO OH OH OH OH not written out. Compare this CH2OH OH OH HO HO notation to the glucose structure in the row above. OH OH OH OH OH OH Polysaccharides Polysaccharides are glucose polymers. All living cells store glucose for energy in the form Animals Plants Yeasts of a polysaccharide. and bacteria Chitin** Glycogen Cellulose** Starch Dextran in invertebrate Humans cannot O O O O HOCH2 HOCH2 HOCH2 animals digest cellulose O O O O O O O O O O O and obtain its O O O O O energy, even O O though it is the O O O HOCH2 HOCH2 HOCH2 CH2 HOCH2 HOCH2 O O O O O O O O O most abundant O O O O O O O O O O O O O polysaccharide on earth. O O O O O O O O Glucose molecules Digestion of starch or glycogen yields **Chitin and cellulose maltose. are structural polysaccharides. 31 FIG. 2.3 REVIEW Biochemistry of Proteins Proteins are polymers of smaller building-block molecules called amino acids. Amino Acids Structure of Peptides and Proteins All amino acids have a carboxyl group (–COOH), an amino group Primary Structure (–NH2), and a hydrogen attached to the same carbon. The fourth bond of the carbon attaches to a variable “R” group. The 20 protein-forming amino acids assemble into polymers called The nitrogen (N) in the amino group peptides. The sequence of amino acids in a peptide chain is called makes proteins our major dietary H the primary structure. Just as the 26 letters of our alphabet O source of nitrogen. combine to create different words, the 20 amino acids can create an NH2 C C almost infinite number of combinations. The R groups differ in their size, shape, and OH R ability to form hydrogen bonds or ions. Because Peptides range in length from two to two million amino acids: of the different R groups, each amino acid Oligopeptide {oligo-, few}: 2–9 amino acids reacts with other molecules in a unique way. Polypeptide: 10–100 amino acids Proteins: >100 amino acids Amino acid Amino acid Sequence of amino acids H H O H H O N C C + N C C H OH H OH Secondary Structure R R Secondary structure Covalent bond angles between amino H 2O is created primarily acids determine secondary structure. by hydrogen bonds In a peptide bond, the between adjacent amino group of one amino chains or loops. H H O H H O acid joins the carboxyl N C C N C C group of the other, with the loss of water. H OH R R a-helix b-strands form sheets Amino Acids in Natural Proteins Tertiary Structure Twenty different amino acids commonly occur in natural proteins. Tertiary structure is the The human body can synthesize most of them, but at different protein’s three-dimensional stages of life some amino acids must be obtained from diet and are shape. therefore considered essential amino acids. Some physiologically important amino acids are listed below. Three-Letter One-Letter Amino Acid Abbreviation Symbol Fibrous proteins Arginine Arg R Collagen Globular proteins Aspartic acid (aspartate)* Asp D Tertiary structures can be a mix of secondary structures. Beta-sheets are shown as flat ribbon Cysteine Cys C arrows and alpha helices are shown as ribbon coils. Glutamic acid (glutamate)* Glu E Glutamine Gln Q Glycine Gly G Quaternary Structure Tryptophan Trp W Multiple subunits combine with noncovalent bonds. Tyrosine Tyr Y Hemoglobin molecules *The suffix -ate indicates the anion form of the acid. are made from four globular protein subunits. Note: A few amino acids do not occur in proteins but have important physiological functions. Homocysteine: a sulfur-containing amino acid that in excess is associated with heart disease g-amino butyric acid (gamma-amino butyric acid) or GABA: a chemical made by nerve cells Creatine: a molecule that stores energy when it binds to a phosphate group Hemoglobin 32  2.1 Molecules and Bonds 33 Ions are the basis for electrical signaling in the body. Ions TABLE 2.1 Common Functional Groups may be single atoms, like the sodium ion Na+ and chloride CHAPTER Notice that oxygen, with two electrons to share, sometimes ion Cl-. Other ions are combinations of atoms, such as the forms a double bond with another atom. bicarbonate ion HCO3-. Important ions of the body are listed Shorthand Bond Structure in TABLE 2.2. H 3. High-energy electrons. The electrons in certain atoms 2 Amino ¬ NH2 N can capture energy from their environment and transfer it to H other atoms. This allows the energy to be used for synthesis, movement, and other life processes. The released energy may O also be emitted as radiation. For example, bioluminescence in Carboxyl (acid) ¬ COOH C fireflies is visible light emitted by high-energy electrons return- OH ing to their normal low-energy state. Hydroxyl ¬ OH O H 4. Free radicals. Free radicals are unstable molecules with an unpaired electron. They are thought to contribute to aging OH and to the development of certain diseases, such as some can- Phosphate ¬ H2PO4 O P O cers. Free radicals and high-energy electrons are discussed in OH Chapter 22. The role of electrons in molecular bond formation is dis- cussed in the next section. There are four common bond types, two strong and two weak. Covalent and ionic bonds are strong Some combinations of elements, known as functional bonds because they require significant amounts of energy to make groups, occur repeatedly in biological molecules. The atoms in or break. Hydrogen bonds and van der Waals forces are weaker a functional group tend to move from molecule to molecule as a bonds that require much less energy to break. Interactions between single unit. For example, hydroxyl groups, -OH, common in many molecules with different bond types are responsible for energy use biological molecules, are added and removed as a group rather and transfer in metabolic reactions as well as a variety of other than as single hydrogen or oxygen atoms. Amino groups, -NH2, reversible interactions. are the signature of amino acids. The phosphate group, -H2PO4, plays a role in many important cell processes, such as energy trans- fer and protein regulation. Addition of a phosphate group is called Covalent Bonds between Atoms Create Molecules phosphorylation; removal of a phosphate group is dephosphorylation. Molecules form when atoms share pairs of electrons, one elec- The most common functional groups are listed in TABLE 2.1. tron from each atom, to create covalent bonds. These strong bonds require the input of energy to break them apart. It is possible to predict how many covalent bonds an atom can form by knowing how many unpaired electrons are in its outer shell, Concept Check because an atom is most stable when all of its electrons are 1. is hree a or essen ia e e en s ound in he hu an ody. paired (FIG. 2.6). 2. ha is he genera or u a o a car ohydra e For example, a hydrogen atom has one unpaired electron 3. ha is he che ica or u a o an a ino group a car o y and one empty electron place in its outer shell. Because hydro- group gen has only one electron to share, it always forms one covalent bond, represented by a single line ( -) between atoms. Oxygen has six electrons in an outer shell that can hold eight. That means oxygen can form two covalent bonds and fill its outer shell with Electrons Have Four Important Biological Roles An atom of any element has a unique combination of protons and electrons that determines the element’s properties (FIG. 2.5). We TABLE 2.2 Important Ions of the Body are particularly interested in the electrons because they play four Cations Anions important roles in physiology: Na+ Sodium Cl- Chloride 1. Covalent bonds. The arrangement of electrons in the outer energy level (shell) of an atom determines an element’s ability K+ Potassium HCO3- Bicarbonate to bind with other elements. Electrons shared between atoms Ca2+ Calcium HPO42- Phosphate form strong covalent bonds that bind atoms together to form molecules. H+ Hydrogen SO42- Sulfate 2. Ions. If an atom or molecule gains or loses one or more Mg2+ Magnesium electrons, it acquires an electrical charge and becomes an ion. FIG. 2.4 REVIEW Nucleotides and Nucleic Acids Nucleotides are biomolecules that play an important role in Nucleotide energy and information transfer. A nucleotide consists of (1) one or more phosphate Single nucleotides include the groups, (2) a 5-carbon sugar, and (3) a carbon-nitrogen energy-transferring compounds ring structure called a ATP (adenosine triphosphate) nitrogenous base. NH2 and ADP (adenosine diphos- C N phate), as well as cyclic AMP, a N C molecule important in the Base CH transfer of signals between cells. HC C O N N Phosphate Nucleic acids (or nucleotide HO CH2 P O polymers) such as RNA and O DNA store and transmit genetic HO information. Sugar HO OH consists of Nitrogenous Bases Five-Carbon Sugars Phosphate Purines Pyrimidines Ribose Deoxyribose have a double ring structure. have a single ring. {de-, without; oxy-, oxygen} H H C HOCH2 O OH HOCH2 O OH O N C N C N CH O– CH HO P HC C HC CH HO N N N H HO OH HO Adenine (A) Guanine (G) Cytosine (C) Thymine (T) Uracil (U) Adenine + Ribose Adenosine Single Nucleotide Molecules Single nucleotide molecules have two critical functions in the human body: (1) Capture and transfer energy in high-energy electrons or phosphate bonds, and (2) aid in cell-to-cell communication. Nucleotide consists of Base + Sugar + Phosphate Groups + Other Component Function ATP = Adenine + Ribose + 3 phosphate groups ADP = Adenine + Ribose + 2 phosphate groups Energy capture and transfer NAD = Adenine + 2 Ribose + 2 phosphate groups + Nicotinamide FAD = Adenine + Ribose + 2 phosphate groups + Riboflavin cAMP = Adenine + Ribose + 1 phosphate group Cell-to-cell communication Nucleic acids (nucleotide 5' end The end of the strand with the polymers) function in unbound phosphate is called information storage and the 5' end. transmission. The sugar of Sugar one nucleotide links to the phosphate of the next, The nitrogenous bases extend creating a chain of alternat- to the side of the chain. ing sugar–phosphate groups. The sugar– phosphate chains, or backbone, are the same for Phosphate every nucleic acid molecule. The end of the strand that has Nucleotide chains form 3' end an unbound sugar is called the strands of DNA and RNA. 3' (“three prime”) end. 5' end Antiparallel orienta- tion: The 3' end of P one strand is bound 3' end to the 5' end of the second strand. T D U A T D A A T A U P P C Nitrogenous C G bases G G C C D U T A G D KEY G G C A Adenine A Sugar–Phosphate P C backbones P T Thymine T A T A G C G D A T G Guanine G Hydrogen D U bonds A T C Cytosine C A G C P P G U Uracil U C C G C D Hydrogen G G C D G bonds U T A Phosphate 3' end P G G C P DNA strand 2 Sugar C 5' end A T A DNA strand 1 RNA (ribonucleic acid) is a DNA (deoxyribonucleic acid) is a double helix, a single–strand nucleic acid three-dimensional structure that forms when two with ribose as the sugar in DNA strands link through hydrogen bonds the backbone, and four between complementary base pairs. Deoxyribose bases—adenine, guanine, is the sugar in the backbone, and the four bases cytosine, and uracil. are adenine, guanine, cytosine, and thymine. Base-Pairing Guanine-Cytosine Base Pair Adenine-Thymine Base Pair Bases on one strand form hydrogen bonds with More energy is bases on the adjoining strand. This bonding follows required to very specific rules: break the triple ecause purines are larger than pyrimidines, space Cytosine hydrogen bonds limitations always pair a purine with a pyrimidine. Guanine Adenine Thymine of G C than uanine forms three hydrogen bonds with the double cytosine (C). bonds of A T Adenine A forms two hydrogen bonds with or A U. thymine (T) or uracil (U). 35 FIG. 2.5 REVIEW Atoms and Molecules Elements are the simplest type of matter. There are over 100 known Major Essential Minor Essential elements,* but only three—oxygen, carbon, and hydrogen—make up more Elements Elements than 90% of the body’s mass. These three plus eight additional elements are major essential elements. An additional 19 minor essential elements are H, C, O, N, Na, Li, F, Cr, Mn, Fe, Co, Ni, Mg, K, Ca, P, Cu, Zn, Se, Y, I, Zr, Nb, required in trace amounts. The smallest particle of any element is an atom S, Cl Mo, Tc, Ru, Rh, La {atomos, indivisible}. Atoms link by sharing electrons to form molecules. * A periodic table of the elements can be found inside the back cover of the book. - Helium (He) has two protons and two Protons: + neutrons, so its determine + + atomic number = 2, the element and its atomic (atomic Helium, He mass = 4 number) - Protons + neutrons in nucleus = Molecules atomic mass Neutrons: determine H the isotope Atoms 2 or more atoms O Such as Electrons: - form covalent bonds share electrons create ions when to form gained or lost in orbitals around the nucleus H capture and store energy create free radicals Water (H2O) Isotopes and Ions An atom that gains or loses neutrons becomes an isotope of the same element. - gains a + - neutron 2H, Hydrogen isotope + loses an 1H, Hydrogen electron + - H+, Hydrogen ion An atom that gains or loses electrons becomes an ion of the same element.  Proteins Amino Amino acid a-helix or Globular or Proteins acids sequence b-strand fibrous shape Ala Val Ser Lys Arg Trp Amino acid sequence Glycoproteins Carbohydrates Monosaccharides Disaccharides Polysaccharides Carbohydrates Lipoproteins O Glycogen Biomolecules O O Starch CH 2 O O O O O O Cellulose O O Polysaccharide Glycolipids Lipids Glycerol Monoglycerides Diglycerides Triglycerides Lipids Fatty acids Lipid-related molecules Phospholipids Eicosanoids Oleic acid, a fatty acid Steroids Nucleotides cAMP, cGMP T A G C A G C C A G ATP, ADP, T T G FAD, NAD A A A C DNA T RNA, DNA G T C molecule 37 FIG. 2.6 REVIEW Molecular Bonds When two or more atoms link by sharing electrons, they make units known as molecules. The transfer of electrons from one atom to another or the sharing of electrons by two atoms is a critical part of forming bonds, the links between atoms. Covalent Bonds Covalent bonds result when atoms share electrons. These bonds require the most energy to make or break. (a) Nonpolar Molecules Nonpolar molecules have an even Hydrogen Fatty acid distribution of electrons. For example, molecules composed mostly of carbon and hydrogen tend to be nonpolar. Carbon (b) Polar Molecules Bonds Polar molecules have regions of Negative pole - - partial charge (d+ or d– ). The most Water molecule - - important example of a polar d– d– - O molecule is water. - - - - - H H d+ d+ O H O H = H H = H 2O Positive pole Noncovalent Bonds (c) Ionic Bonds Ionic bonds are electrostatic attractions between ions. A common example is sodium chloride. + – Na CI Na CI Sodium ion (Na+ ) Sodium atom Chlorine atom Chloride ion (CI– ) Sodium gives up its one weakly held electron The sodium and chloride ions both have stable to chlorine, creating sodium and chloride ions, outer shells that are filled with electrons. Because Na+ and Cl-. of their opposite charges, they are attracted to each other and, in the solid state, the ionic bonds form a sodium chloride (NaCl) crystal. (d) Hydrogen Bonds Hydrogen bonds form between a hydrogen atom and a nearby oxygen, nitrogen, or fluorine atom. So, for example, the polar regions of adjacent water molecules allow them to form hydrogen bonds with Hydrogen one another. bonding Hydrogen bonding between water molecules is responsible for the surface tension of water. (e) Van der Waals Forces Van der Waals forces are weak, nonspecific attractions between atoms. 38  2.1 Molecules and Bonds 39 Noncovalent Bonds Facilitate RUNNING PROBLEM Reversible Interactions CHAPTER What is chromium picolinate? Chromium (Cr) is an essential ele- Ionic bonds, hydrogen bonds, and van der Waals forces are ment that has been linked to normal glucose metabolism. In the noncovalent bonds. They play important roles in many physiologi- diet, chromium is found in brewer’s yeast, broccoli, mushrooms, and apples. Because chromium in food and in chromium chlo- cal processes, including pH, molecular shape, and the reversible 2 ride supplements is poorly absorbed from the digestive tract, a binding of molecules to each other. scientist developed and patented the compound chromium pico- Ionic Bonds Ions form when one atom has such a strong attraction linate. Picolinate, derived from amino acids, enhances chromium for electrons that it pulls one or more electrons completely away uptake at the intestine. The recommended adequate intake (AI) from another atom. For example, a chlorine atom needs only one of chromium for men ages 19–50 is 35 mg/day. (For women, it is electron to fill the last of eight places in its outer shell, so it pulls 25 mg/day.) As we’ve seen, Stan takes more than 10 times this an electron from a sodium atom, which has only one weakly held amount. electron in its outer shell (Fig. 2.6c). The atom that gains electrons Q1: Locate chromium on the periodic table of the elements. acquires one negative charge ( -1) for each electron added, so the What is chromium’s atomic number? Atomic mass? How many chlorine atom becomes a chloride ion Cl-. Negatively charged ions electrons does one atom of chromium have? Which elements are called anions. close to chromium are also essential elements? An atom that gives up electrons has one positive charge ( +1) 29 39 40 41 46 48 53 for each electron lost. For example, the sodium atom becomes a sodium ion Na+. Positively charged ions are called cations. Ionic bonds, also known as electrostatic attractions, result from the attraction between ions with opposite charges. (Remember the electrons. If adjacent atoms share two pairs of electrons rather basic principle of electricity that says that opposite charges attract than just one pair, a double bond, represented by a double line and like charges repel.) In a crystal of table salt, the solid form of ( “ ), results. If two atoms share three pairs of electrons, they ionized NaCl, ionic bonds between alternating Na+ and Cl- ions form a triple bond. hold the ions in a neatly ordered structure. Polar and Nonpolar Molecules Some molecules develop regions of Hydrogen Bonds A hydrogen bond is a weak attractive force partial positive and negative charge when the electron pairs in their between a hydrogen atom and a nearby oxygen, nitrogen, or fluo- covalent bonds are not evenly shared between the linked atoms. rine atom. No electrons are gained, lost, or shared in a hydrogen When electrons are shared unevenly, the atom(s) with the stronger bond. Instead, the oppositely charged regions in polar molecules attraction for electrons develops a slight negative charge (indicated are attracted to each other. Hydrogen bonds may occur between by d + ), and the atom(s) with the weaker attraction for electrons atoms in neighboring molecules or between atoms in different develops a slight positive charge (d -). These molecules are called parts of the same molecule. For example, one water molecule may polar molecules because they can be said to have positive and hydrogen-bond with as many as four other water molecules. As a negative ends, or poles. Certain elements, particularly nitrogen and result, the molecules line up with their neighbors in a somewhat oxygen, have a strong attraction for electrons and are often found ordered fashion (Fig. 2.6d). in polar molecules. Hydrogen bonding between molecules is responsible for the A good example of a polar molecule is water (H2O). surface tension of water. Surface tension is the attractive force The larger and stronger oxygen atom pulls the hydrogen elec- between water molecules that causes water to form spherical drop- trons toward itself (Fig. 2.6b). This pull leaves the two hydro- lets when falling or to bead up when spilled onto a nonabsorbent gen atoms of the molecule with a partial positive charge, and surface (Fig. 2.6d). The high cohesiveness {cohaesus, to cling together} the single oxygen atom with a partial negative charge from the of water is due to hydrogen bonding and makes it difficult to stretch unevenly shared electrons. Note that the net charge for the entire or deform, as you may have noticed in trying to pick up a wet glass water molecule is zero. The polarity of water makes it a good that is “stuck” to a slick table top by a thin film of water. The surface solvent, and all life as we know it is based on watery, or aqueous, tension of water influences lung function (described in Chapter 17). solutions. A nonpolar molecule is one whose shared electrons are Van der Waals Forces Van der Waals forces are weak, nonspe- distributed so evenly that there are no regions of partial positive cific attractions between the nucleus of any atom and the electrons or negative charge. For example, molecules composed mostly of nearby atoms. Two atoms that are weakly attracted to each of carbon and hydrogen, such as the fatty acid shown in Figure other by van der Waals forces move closer together until they are 2.6a, tend to be nonpolar. This is because carbon does not attract so close that their electrons begin to repel one another. Conse- electrons as strongly as oxygen does. As a result, the carbons and quently, van der Waals forces allow atoms to pack closely together hydrogens share electrons evenly, and the molecule has no regions and occupy a minimum amount of space. A single van der Waals of partial charge. attraction between atoms is very weak. 40 CHAPTER 2 Molecular Interactions proportion. All molecules and cell components are either dissolved RUNNING PROBLEM or suspended in these solutions. For these reasons, it is useful to One advertising claim for chromium is that it improves the understand the properties of solutions, which are reviewed in transfer of glucose—the simple sugar that cells use to fuel all FIGURE 2.7. their activities—from the bloodstream into cells. In people with The degree to which a molecule is able to dissolve in a solvent diabetes mellitus, cells are unable to take up glucose from the is the molecule’s solubility: the more easily a molecule dissolves, blood efficiently. It seemed logical, therefore, to test whether the the higher its solubility. Water, the biological solvent, is polar, so addition of chromium to the diet would enhance glucose uptake molecules that dissolve readily in water are polar or ionic molecules in people with diabetes. In one Chinese study, diabetic patients whose positive and negative regions readily interact with water. receiving 500 micrograms (mg) of chromium picolinate twice a For example, if NaCl crystals are placed in water, polar regions day showed significant improvement in their glucose uptake, but of the water molecules disrupt the ionic bonds between sodium patients receiving 100 micrograms or a placebo did not. and chloride, which causes the crystals to dissolve (FIG. 2.8a). Mol- Q2: If people have a chromium deficiency, would you predict ecules that are soluble in water are said to be hydrophilic {hydro-, that their blood glucose level would be lower or higher than nor- water + @philic, loving}. mal? From the results of the Chinese study, can you conclude In contrast, molecules such as oils that do not dissolve well in that all people with diabetes suffer from a chromium deficiency? water are said to be hydrophobic {-phobic, hating}. Hydrophobic substances are usually nonpolar molecules that cannot form hydro- 29 39 40 41 46 48 53 gen bonds with water molecules. The lipids (fats and oils) are the most hydrophobic group of biological molecules. When placed in an aqueous solution, lipids do not dissolve. Concept Check Instead they separate into distinct layers. One familiar example is salad oil floating on vinegar in a bottle of salad dressing. Before 4. re e ec rons in an a o or o ecu e os s a e when hey are paired or unpaired hydrophobic molecules can dissolve in body fluids, they must 5. When an atom of an element gains or loses one or more elec- combine with a hydrophilic molecule that will carry them into trons, it is called a(n) of that element. solution. 6. a ch each ype o ond wi h i s descrip ion For example, cholesterol, a common animal fat, is a hydropho- bic molecule. Fat from a piece of meat dropped into a glass of warm a co a en ond. weak a rac i e orce e ween hydro- water will float to the top, undissolved. In the blood, cholesterol will gen and o ygen or ni rogen not dissolve unless it binds to special water-soluble carrier molecules. (b) ionic bond 2. formed when two atoms share one or You may know the combination of cholesterol with its hydrophilic more pairs of electrons carriers as HDL-cholesterol and LDL-cholesterol, the “good” and c hydrogen ond. weak a rac i e orce e ween a o s “bad” forms of cholesterol associated with heart disease. d an der aa s 4. formed when one atom loses one or Some molecules, such as the phospholipids, have both polar force more electrons to a second atom and nonpolar regions (Fig. 2.8b). This dual nature allows them to associate both with each other (hydrophobic interactions) and with polar water molecules (hydrophilic interactions). Phospholipids are the primary component of biological membranes. 2.2 Noncovalent Interactions Many different kinds of noncovalent interactions can take place between and within molecules as a result of the four different Concept Check types of bonds. For example, the charged, uncharged, or partially 7. hich disso e ore easi y in wa er po ar o ecu es or non charged nature of a molecule determines whether that molecule po ar o ecu es can dissolve in water. Covalent and noncovalent bonds determine 8. o ecu e ha disso es easi y is said o e hydro ic. molecular shape and function. Finally, noncovalent interactions 9. hy does a e sa a disso e in wa er allow proteins to associate reversibly with other molecules, creat- ing functional pairings such as enzymes and substrates, or signal receptors and molecules. Molecular Shape Is Related to Molecular Function A molecule’s shape is closely related to its function. Molecular Hydrophilic Interactions Create bonds—both covalent bonds and weak bonds—play a critical role Biological Solutions in determining molecular shape. The three-dimensional shape of Life as we know it is established on water-based, or aqueous, solu- a molecule is difficult to show on paper, but many molecules have tions that resemble dilute seawater in their ionic composition. characteristic shapes due to the angles of covalent bonds between The adult human body is about 60% water. Na+, K+, and Cl- are the atoms. For example, the two hydrogen atoms of the water the main ions in body fluids, with other ions making up a lesser molecule shown in Figure 2.6b are attached to the oxygen with. onco a en n erac ions 41 a bond angle of 104.5°. Double bonds in long carbon chain fatty acids cause the chains to kink or bend, as shown by the three- RUNNING PROBLEM CHAPTER dimensional model of oleic acid in Figure 2.5. Chromium is found in several ionic forms. The chromium usually Weak noncovalent bonds also contribute to molecular found in biological systems and in dietary supplements is the cat- shape. The complex double helix of a DNA molecule, shown in ion Cr 3+. This ion is called trivalent because it has a net charge of Figure 2.4, results both from covalent bonds between adjacent +3. The hexavalent cation, Cr 6+, with a charge of +6, is used in 2 bases in each strand and the hydrogen bonds connecting the two industry, such as in the manufacturing of stainless steel and the strands of the helix. chrome plating of metal parts. Proteins have the most complex and varied shapes of all the Q3: How many electrons have been lost from the hexavalent biomolecules. Their shapes are determined both by the sequence ion of chromium? From the trivalent ion? of amino acids in the protein chain (the primary structure of the protein) plus varied noncovalent interactions as long poly- 29 39 40 41 46 48 53 peptide chains loop and fold back on themselves. The stable secondary structures of proteins are formed by covalent bond can change. A change in shape may alter or destroy the molecule’s angles between amino acids in the polypeptide chain. ability to function. The two common protein secondary structures are the The concentration of free H+ in body fluids, or acidity, is mea- A@helix (alpha-helix) spiral and the zigzag shape of B@sheets sured in terms of pH. FIGURE 2.9 reviews the chemistry of pH and (Fig. 2.3). Adjacent b@strands in the polypeptide chain associate into shows a pH scale with the pH values of various substances. The sheetlike structures held together by hydrogen bonding, shown as normal pH of blood in the human body is 7.40, slightly alkaline. dotted lines (...) in Figure 2.3. The sheet configuration is very Regulation of the body’s pH within a narrow range is critical stable and occurs in many proteins destined for structural uses. because a blood pH more acidic than 7.00 (pH 6 7.00) or more Proteins with other functions may have a mix of b@strands and alkaline than 7.70 (pH 7 7.70) is incompatible with life. a@helices. Protein secondary structure is illustrated by ribbon dia- Where do hydrogen ions in body fluids come from? Some of grams (or Richardson diagrams), with beta-sheets shown as flat them come from the separation of water molecules (H2O) into H+ arrows and a@helices as ribbon spirals (Fig. 2.3). and OH- ions. Others come from acids, molecules that release H+ The tertiary structure of a protein is its three-dimensional when they dissolve in water (Fig. 2.9). Many of the molecules made shape, created through spontaneous folding as the result of covalent during normal metabolism are acids. For example, carbonic acid is bonds and noncovalent interactions. Proteins are categorized into made in the body from CO2 (carbon dioxide) and water. In solution, two large groups based on their shape: globular and fibrous (see carbonic acid separates into a bicarbonate ion and a hydrogen ion: Fig. 2.3). Globular proteins can be a mix of a@helices, b-sheets, CO2 + H2O L H2CO3 (carbonic acid) L H+ + HCO3- and amino acid chains that fold back on themselves. The result is a complex tertiary structure that may contain pockets, channels, or protruding knobs. The tertiary structure of globular proteins arises Note that when the hydrogen is part of the intact carbonic partly from the angles of covalent bonds between amino acids and acid molecule, it does not contribute to acidity. Only free H + contrib- partly from hydrogen bonds, van der Waals forces, and ionic bonds utes to the hydrogen ion concentration. that stabilize the molecule’s shape. We are constantly adding acid to the body through metabolism, In addition to covalent bonds between adjacent amino acids, so how does the body maintain a normal pH? One answer is buf- covalent disulfide (S - S) bonds play an important role in the fers. A buffer is any substance that moderates changes in pH. shape of many globular proteins (Fig. 2.8c). The amino acid cysteine Many buffers contain anions that have a strong attraction for H+ contains sulfur as part of a sulfhydryl group ( -SH). Two cysteines molecules. When free H+ is added to a buffer solution, the buffer’s in different parts of the polypeptide chain can bond to each other anions bond to the H+, thereby minimizing any change in pH. with a disulfide bond that pulls the sections of chain together. The bicarbonate anion, HCO3-, is an important buffer in the Fibrous proteins can be b@strands or long chains of human body. The following equation shows how a sodium bicar- a@helices. Fibrous proteins are usually insoluble in water and form bonate solution acts as a buffer when hydrochloric acid (HCl) is important structural components of cells and tissues. Examples of added. When placed in plain water, hydrochloric acid separates, or fibrous proteins include collagen, found in many types of connective dissociates, into H+ and Cl- and creates a high H+ concentration tissue, such as skin, and keratin, found in hair and nails. (low pH). When HCl dissociates in a sodium bicarbonate solution, however, some of the bicarbonate ions combine with some of the Hydrogen Ions in Solution Can Alter H+ to form undissociated carbonic acid. “Tying up” the added H+ in this way keeps the free H+ concentration of the solution from Molecular Shape changing significantly and minimizes the pH change. Hydrogen bonding is an important part of molecular shape. How- ever, free hydrogen ions, H+, in solution can also participate in H+ + Cl- + HCO3- + Na+ L H2CO3 + Cl- + Na+ hydrogen bonding and van der Waals forces. If free H+ disrupts a L Hydrochloric Sodium Carbonic Sodium chloride + + acid bicarbonate acid (table salt) molecule’s noncovalent bonds, the molecule’s shape, or conformation, FIG. 2.7 REVIEW Solutions Life as we know it is established on water-based, or aqueous, solutions that resemble dilute seawater in their ionic composition. The human body is 60% water. Sodium, potassium, and chloride are the main ions in body fluids. All molecules and cell compo- nents are either dissolved or suspended in these saline solutions. For these reasons, the properties of solutions play a key role in the functioning of the human body. Terminology A solute is any substance that dissolves in a liquid. The degree to which a molecule is able to dissolve in a solvent is the molecule’s solubility. The more easily a solute dissolves, the higher its solubility. A solvent is the liquid into which solutes dissolve. In biological solutions, water is the universal solvent. A solution is the combination of solutes dissolved in a solvent. The concentration of a solution is the amount of solute per unit volume of solution. Concentration = solute amount/volume of solution Expressions of Solute Amount FIGURE QUESTIONS 1. What are the two Mass (weight) of the solute before it dissolves. Usually given in grams (g) or milligrams (mg). components of a solution? 2. The concentration of a Molecular mass is calculated from the chemical formula of a molecule. This is the mass of one solution is expressed as: molecule, expressed in atomic mass units (amu) or, more often, in daltons (Da), where 1 amu = 1 Da. (a) amount of solvent/volume of solute atomic mass the number of atoms (b) amount of solute/volume Molecular mass = SUM of each element × of each element of solvent (c) amount of solvent/volume of solution (d) amount of solute/volume of solution Example 3. Calculate the molecular mass of water, H2O. What is the Answer molecular mass