Biochemistry can be defined as the science of the chemical basis of life (Gk bios "life"). The cell is the structural unit of living systems. Thus, biochemistry can also be described as the science ofthe chemical constituents of living cells and of the reactions and processes they undergo. By this definition, biochemistry encompasses large areas of cell biology, molecular biology, and molecular genetics.The major objective of biochemistry is the complete understanding, at the molecular level, of all ofthe chemical processes associated ith living cells. To achieve this objective, biochemists have sought to isolate the numerous molecules found in cells, determine their structures, and analy!e ho they function.Water is the predominant chemical component of living organisms."ni#ue physical properties$the ability to solvate a ide range of organic and inorganic molecules derive from ater%s dipolar structure and e&ceptional capacity for forming hydrogen bonds. 'ater has a slight propensity to dissociate into hydro&ide ions and protons. The acidity of a#ueous solutions is generally reported using the logarithmic p( scale. Bicarbonate and other buffers normally maintain the p( of e&tracellular fluid beteen ).*+ and ).,+. -uspected disturbances of acid.base balance are verified by measuring the p( of arterial blood and the /01 content of venous blood. /auses of acidosis (blood p( 2).*+) include diabetic ketosis and lactic acidosis. 3lkalosis (p(4).,+) may follo vomiting of acidic gastric contents. 5egulation of ater balance depends upon hypothalamic mechanisms that control thirst, on antidiuretic hormone (36(), on retention or e&cretion of ater by the kidneys, and on evaporative loss. 7ephrogenic diabetes insipidus, hich involves the inability to concentrate urine or adjust to subtle changes in e&tracellular fluid osmolarity, results from the unresponsiveness of renal tubular osmoreceptors to 36(.Water Molecules Form Dipoles-3 ater molecule is an irregular, slightly skeed tetrahedron ith o&ygen at its center. 3mmonia is also tetrahedral, ith a 89)$ degree angle beteen its hydrogens. 'ater is a dipole, a molecule ith electrical charge distributed asymmetrically about its structure. The strongly electronegative o&ygen atom pulls electrons aay from the hydrogen nuclei, leaving them ith a partial positive charge, hile its to unshared electron pairs constitute a region of local negative charge.'ater, a strong dipole, has a high dielectric constant. 3s described #uantitatively by /oulomb:s la, strength of interaction ; beteen oppositely charged particles is inversely proportionate to the dielectric constant < of the surrounding medium. The dielectric constant for a vacuum is unity$)=.+. 'ater therefore greatly decreases the force of attraction beteen charged and polar speciesrelative to ater$free environments ith loer dielectric constants. >ts strong dipole and high dielectric constant enable ater to dissolve large #uantities of charged compounds such as salts. The covalent bond is the strongest force that holds molecules together. 7oncovalent forces, hile of lesser magnitude, make significant contributions to the structure, stability, and functional competence of macromolecules in living cells. These forces, hich can be either attractive or repulsive, involve interactions both ithin the biomolecule and beteen it and the ater that formsthe principal component of the surrounding environment.?ost biomolecules are amphipathic; that is, they possess regions rich in charged or polar functional groups as ell as regions ith hydrophobic character. @roteins tend to fold ith the 5$groups of amino acids ith hydrophobic side chains in the interior. 3mino acids ith charged or polar amino acid side chains (eg, arginine, glutamate,serine) generally are present on the surface in contact ith ater. 3 similar pattern prevails in a phospholipid bilayer, here the charged head groups of phosphatidyl serine or phosphatidyl ethanolamine contact ater hile their hydrophobicfatty acyl side chains cluster together, e&cluding ater. This pattern ma&imi!es the opportunities for the formation of energetically favorable charge.dipole,dipole.dipole, and hydrogen bonding interactions beteen polar groups on the biomolecule and ater. >t also minimi!es energetically unfavorable contacts beteen ater and hydrophobic groups.(ydrophobic interaction refers to the tendency of nonpolar compounds to self$associate in an a#ueous environment. This self$association is driven neither by mutual attraction nor by hat are sometimes incorrectly referred to as "hydrophobic bonds." -elf$association minimi!es energetically unfavourable interactions beteen nonpolar groups and ater. 'hile the hydrogens of nonpolar groups such as the methylene groups of hydrocarbons do not form hydrogen bonds, they do affect the structure of the ater that surrounds them. 'ater molecules adjacent to a hydrophobic group are restricted in the number of orientations (degrees of freedom) that permit them to participate in the ma&imum number of energetically favorable hydrogen bonds. ?a&imal formation of multiple hydrogen bonds can be maintained only by increasing the order of the adjacent ater molecules, ith an accompanying decrease in entropy. >t follos from the second la of thermodynamics that the optimal free energy of a hydrocarbon.ater mi&ture is a function of both ma&imal enthalpy (from hydrogen bonding) and minimum entropy (ma&imum degrees of freedom). Thus, nonpolar molecules tend to form droplets in order to minimi!e e&posed surface area and reduce the number of ater molecules affected. -imilarly, in the a#ueous environment ofthe living cell the hydrophobic portions of biopolymers tend to be buried inside the structure of the molecule, or ithin a lipid bilayer, minimi!ing contact ith ater.Electrostatic Interactions >nteractions beteen charged groups help shape biomolecular structure. Alectrostatic interactions beteen oppositely charged groups ithin or beteen biomolecules are termed salt bridges. -alt bridges are comparable in strength to hydrogen bonds but act over larger distances. They therefore often facilitate the binding of charged molecules and ions to proteins and nucleic acids.van der Waals forces arise from attractions beteen transient dipoles generated by the rapid movement of electrons of all neutral atoms. -ignificantly eaker than hydrogen bonds but potentially e&tremely numerous, van der 'aals forces decrease as the si&th poer of the distanceseparating atoms. Thus, they act over very short distances, typically 1., B. Multiple Forces Stabilize BiomoleculesThe 673 double heli& illustrates the contribution of multiple forces to the structure of biomolecules. 'hile each individual 673 strand is held together by covalent bonds, the to strands of the heli& are held together e&clusively by noncovalent interactions. These noncovalent interactions include hydrogen bonds beteen nucleotide bases ('atson./rick base pairing) and van der 'aals interactions beteen the stacked purine and pyrimidine bases. The heli& presents the charged phosphate groups and polar ribose sugars of the backbone to ater hile burying therelatively hydrophobic nucleotide bases inside. The e&tended backbone ma&imi!es the distance beteen negatively charged phosphates, minimi!ing unfavourable electrostatic interactions.The major carbohydrates in the human diet are starch, sucrose, lactose, fructose, and glucose. The polysaccharide starch is the storage form of carbohydrates in plants. -ucrose (table sugar) and lactose (milk sugar) are disaccharides, and fructose and glucose are monosaccharides. 6igestion converts the larger carbohydrates to monosaccharides, hich can be absorbed into the bloodstream. Glucose, a monosaccharide, is the predominant sugar in human blood (;ig. 8.,). 0&idation of carbohydrates to /01 and (10 in the body produces appro&imately , kcalCg. >n other ords, every gram of carbohydrate e eat yields appro&imately , kcal of energy. 7ote that carbohydrate molecules contain a significant amount of o&ygen and are already partially o&idi!ed before they enter our bodies. roteins are composed of amino acids that are joined to form linear chains. >n addition to carbon,hydrogen, and o&ygen, proteins contain appro&imately 8DE nitrogen by eight. The digestive process breaks don proteins to their constituent amino acids, hich enter the blood. The complete o&idation of proteins to /01, (10, and 7(, F in the body yields appro&imately , kcalCg.Fats are lipids composed of triacylglycerols (also called triglycerides). 3 triacylglycerol molecule contains * fatty acids esterified to one glycerol moiety. ;ats contain much less o&ygen than is contained in carbohydrates or proteins.Therefore, fats are more reduced and yield more energy hen o&idi!ed. The complete o&idation of triacylglycerols to /01 and (10 in the body releases appro&imately G kcalCg, more than tice the energy yield from an e#uivalent amount of carbohydrate or protein.!. "lcohol ?any people used to believe that alcohol (ethanol, in the conte&t of the diet) has no caloric content. >n fact, ethanol (/(*/(10() is o&idi!ed to /01 and (10 in the body and yields appro&imately ) kcalCgHthat is, more than carbohydrate but less than fat.II. B#!$ F%E& S'#(ES3lthough some of us may try, it is virtually impossible to eat constantly. ;ortunately, e carry supplies of fuel ithin our bodies (;ig. 8.)). These fuel stores are light in eight, large in #uantity, and readily converted into o&idi!able substances. ?ost of us are familiar ith fat, our major fuel store, hich is located in adipose tissue. 3lthough fat is distributed throughout our bodies, it tends to increase in #uantity in our hips and thighs and in our abdomens as e advance into middle age. >n addition to our fat stores, e also have important, although much smaller, stores of carbohydrate in the form of glycogen located primarily in our liver and muscles. Glycogen consistsof glucose residues joined together to form a large, branched polysaccharide. Body protein, particularly the protein of our large muscle masses, also serves to some e&tent as a fuel store, and e dra on it for energy hen e fast.". Fat. 0ur major fuel store is adipose triacylglycerol (triglyceride), a lipid more commonly knon as fat. The average )9$kg man has appro&imately 8+ kg stored triacylglycerol, hich accounts for appro&imately =+E of his total stored calories (see ;ig. 8.)). To characteristics make adipose triacylglycerol a very efficient fuel storeI the fact that triacylglycerol contains more calories per gram than carbohydrate or protein (G kcalCg versus , kcalCg) and the fact that adipose tissue does not contain much ater. 3dipose tissue contains only about 8+E ater, compared to tissues such as muscle that contain about =9E. Thus, the )9$kg man ith 8+ kg stored triacylglycerol has only about 8= kg adipose tissue.B. )lycogen. 0ur stores of glycogen in liver, muscle, and other cells are relatively small in #uantity but are nevertheless important. Jiver glycogen is used to maintain blood glucose levels beteen meals. Thus, the si!e of this glycogen store fluctuates during the dayK an average )9$kg man might have 199 g or more of liver glycogen after a meal but only =9 g after an overnight fast. ?uscle glycogen supplies energy for muscle contraction during e&ercise. 3t rest, the )9$kg man has appro&imately 8+9 g of muscle glycogen. 3lmost all cells, including neurons, maintain a small emergency supply of glucose as glycogen.*. rotein. @rotein serves many important roles in the bodyK unlike fat and glycogen, it is not solely a fuel store. ?uscle protein is essential for body movement. 0ther proteins serve as en!ymes (catalysts of biochemical reactions) or as structural components of cells and tissues. 0nly a limited amount of body protein can be degraded, appro&imately D kg in the average )9$kg man, before our body functions are compromised. BI#ME!I*"& IM#('"+*E>n addition to providing the monomer units from hich the long polypeptide chains of proteins are synthesi!ed, theJ $ $amino acids and their derivatives participate in cellular functions as diverse as nerve transmission and the biosynthesis of porphyrins, purines, pyrimidines, and urea. -hort polymers of amino acids called peptides perform prominent roles in the neuroendocrine system as hormones, hormone$releasing factors, neuromodulators, or neurotransmitters. 'hile proteins contain only J $ $amino acids, microorganisms elaborate peptides that contain both 6 $ and J $ $amino acids. -everal of these peptides are of therapeutic value, including the antibiotics bacitracin and gramicidin 3 and the antitumor agent bleomycin. /ertain other microbial peptides are to&ic. The cyanobacterial peptides microcystin and nodularin are lethal in large doses, hile small #uantities promote the formation of hepatic tumors. (umans and other higher animals lack the capability to synthesi!e 89 of the 19 common J $ $amino acids in amounts ade#uate to supportinfant groth or to maintain health in adults. /onse#uently, the human diet must contain ade#uate#uantities of these nutritionally essential amino acids. (#E('IES #F "MI+# "*I!S'he )enetic *ode Speci,ies -. & / /"mino "cids0f the over *99 naturally occurring amino acids, 19 constitute the monomer units of proteins. 'hile anonredundant three$letter genetic code could accommodate more than 19 amino acids, its redundancy limits the available codons to the 19 J $ $amino acids listed in Table *.8, classified according to the polarity of their 5 groups. Both one$ and three$letter abbreviations for each aminoacid can be used to represent the amino acids in peptides and proteins. -ome proteins contain additional amino acids that arise by modification of an amino acid already present in a peptide. A&amples include conversion of peptidyl proline and lysine to ,$ hydro&yproline and +$hydro&ylysineK the conversion of peptidyl glutamate to $carbo&yglutamateK and the methylation, formylation, acetylation, prenylation, and phosphorylation of certain aminoacyl residues. These modifications e&tend the biologic diversity of proteins by altering their solubility, stability, and interaction ith other proteins.Selenocysteine, the -0st & / /"mino "cid1-elenocysteine is an J $ $amino acid found in a handful of proteins, including certain pero&idases and reductases here it participates in the catalysis of electron transfer reactions. 3s its name implies, a selenium atom replaces the sulfur of its structural analog, cysteine. The pK 3 of selenocysteine, +.1, is * units loer than that of cysteine. -ince selenocysteine is inserted into polypeptides during translation, it is commonly referred to as the "18st amino acid." (oever, unlike the other 19 genetically encoded amino acids, selenocysteine is not specified by a simple three$letter codon.#nly & / /"mino "cids #ccur in roteins'ith the sole e&ception of glycine, the $carbon of amino acids is chiral. 3lthough some protein amino acids are de&trorotatory and some levorotatory, all share the absolute configuration of J $glyceraldehyde and thus are J $ $ amino acids. -everal free J $ $amino acids fulfill important roles in metabolic processes. A&amples include ornithine, citrulline, and argininosuccinate that participate in urea synthesisK tyrosine in formation of thyroid hormonesK and glutamate in neurotransmitter biosynthesis. 6 $3mino acids that occur naturally include free 6 $serine and 6 $aspartate in brain tissue, 6 $alanine and 6 $glutamate in the cell alls of gram$positive bacteria, and 6 $amino acids in certain peptides and antibiotics produced by bacteria, fungi, reptiles, and other nonmammalianspecies.22"mino "cids May 3ave ositive, +egative, or 4ero +et *hargepK a 5alues E6press the Strengths o, Wea7 "cids. The acid strengths of eak acids are e&pressed as their p K a . ;or molecules ith multiple dissociable protons, the pK a for each acidic group is designated by replacing the subscript "a" ith a number. The imida!ole group of histidine and the guanidino group of arginine e&ist as resonance hybrids ith positive charge distributed beteen both nitrogens (histidine) or all three nitrogens (arginine). The net charge on an amino acidHthe algebraic sum of all the positively and negatively charged groups presentHdepends upon the pK a values of its functional groups and on the p( of the surrounding medium. 3ltering the charge on amino acids and their derivatives by varying the p( facilitates the physical separation of amino acids, peptides, and proteins. 'he Solubility o, "mino "cids (e,lects 'heir Ionic *haracter. The charged functional groups of amino acids ensure that they are readily solvated byHand thus soluble inHpolar solvents such as ater and ethanol but insoluble in nonpolar solvents such as ben!ene, he&ane, or ether.3mino acids do not absorb visible light and thus are colorless. (oever, tyrosine, phenylalanine, and especially tryptophan absorb high$avelength (1+9.1G9 nm) ultraviolet light. Because it absorbs ultraviolet light about ten times more efficiently than either phenylalanine or tyrosine, tryptophan makes the major contribution to the ability of most proteins to absorb light in the regionof 1=9 nm.'3E /( )(#%S !E'E(MI+E '3E (#E('IES #F "MI+# "*I!S-ince glycine, the smallest amino acid, can be accommodated in places inaccessible to other amino acids, it often occurs here peptides bend sharply. The hydrophobic 5 groups of alanine, valine, leucine, and isoleucine and the aromatic 5 groups of phenylalanine, tyrosine, and tryptophan typically occur primarily in the interior of cytosolic proteins. The charged 5 groups of basic and acidic amino acids stabili!e specific protein conformations via ionic interactions, or salt bridges. These interactions also function in "charge relay" systems during en!ymatic catalysis andelectron transport in respiring mitochondria. (istidine plays uni#ue roles in en!ymatic catalysis. The pK a of its imida!ole proton permits it to function at neutral p( as either a base or an acid catalyst. The primary alcohol group of serine and the primary thioalcohol (H-() group of cysteineare e&cellent nucleophiles and can function as such during en!ymatic catalysis. (oever, the secondary alcohol group of threonine, hile a good nucleophile, does not fulfill an analogous role in catalysis. The H0( groups of serine, tyrosine, and threonine also participate in regulation of the activity of en!ymes hose catalytic activity depends on the phosphorylation state of these residues.eptides "re olyelectrolytes. The peptide bond is uncharged at any p( of physiologic interest. ;ormation of peptides from amino acids is therefore accompanied by a net loss of one positive and one negative charge per peptide bond formed. @eptides nevertheless are charged at physiologic p( oing to their carbo&yl and amino terminal groups and, here present, their acidic or basic 5 groups. 3s for amino acids, the net charge on a peptide depends on the p( of its environment and on the pK a value of its dissociating groups.