Chapter 1 The Foundations of Biochemistry Although complex, this organization of the cyto- reversible, and subject to regulation in response to var- plasm is far from random. The motion and the position- ious intracellular and extracellular si ing of organelles and cytoskeletal elements are under tight regulation, and at certain stages in a eukaryotic Cells Build Supramolecular Structures cells life, dramatic, finely orchestrated reorganizations, Macromolecules and their monomeric subunits differ such as the events of mitosis occur. The interactions be. tween the cytoskeleton and organelles are noncovalent greatly in size(Fig 1-10). A molecule of alanine is less han 0.5 nm long Hemoglobin, the oxygen-carrying pro- tein of erythrocytes (red blood cells), consists of nearly (a)Some of the amino acids of proteins 600 amino acid subunits in four long chains, folded into globular shapes and associated in a structure 5.5 nm in diameter. In turn, proteins are much smaller than ribo- somes (about 20 nm in diameter), which are in turn HSN HSN-C-E much smaller than organelles such as mitochondria, typ- OI CH? ically 1, 000 nm in diameter. It is a long jump from sim Alanine Serine ple biomolecules to cellular structures that can be seen Coo HaN-C-H FIGURE 1-10 ds from which most cellular HSN-C-H materials are constructed: the ABCs of biochemistry. Shown here are (a)six of the 20 amino acids from which all proteins are built(the side chains are shaded pink);(b)the five nitrogenous bases, two five. SHI carbon sugars, and phosphoric acid from which all nucleic acids are Oyster built;(c)five components of membrane lipids; and (d)D-glucose, the parent sugar from which most carbohydrates are derived. Note that hosphoric acid is a component of both nucleic acids and membrane Tyrosine (b) The components of nucleic acids (e) Some components of lipids NH2 COO CH,OH CHs HOH N CH CH CH CHs CH.-N-CH CH.OH NH2 CH CH HoN Adenine i Phosphoric ac> CH2 (d) The parent sugar Nitrogenous bases CH HOCHo O HOH CH3 OHOH OH H Palmitate a-D.Ribos OH Five-carbon sugars Oleate
Although complex, this organization of the cytoplasm is far from random. The motion and the positioning of organelles and cytoskeletal elements are under tight regulation, and at certain stages in a eukaryotic cell’s life, dramatic, finely orchestrated reorganizations, such as the events of mitosis, occur. The interactions between the cytoskeleton and organelles are noncovalent, reversible, and subject to regulation in response to various intracellular and extracellular signals. Cells Build Supramolecular Structures Macromolecules and their monomeric subunits differ greatly in size (Fig. 1–10). A molecule of alanine is less than 0.5 nm long. Hemoglobin, the oxygen-carrying protein of erythrocytes (red blood cells), consists of nearly 600 amino acid subunits in four long chains, folded into globular shapes and associated in a structure 5.5 nm in diameter. In turn, proteins are much smaller than ribosomes (about 20 nm in diameter), which are in turn much smaller than organelles such as mitochondria, typically 1,000 nm in diameter. It is a long jump from simple biomolecules to cellular structures that can be seen 10 Chapter 1 The Foundations of Biochemistry Uracil Thymine -D-Ribose 2-Deoxy- -D-ribose O H OH NH2 HOCH2 Cytosine H H H OH H O H OH HOCH2 H H H OH OH Adenine Guanine COO Oleate Palmitate H CH2OH O HO OH -D-Glucose H H H OH OH H (b) The components of nucleic acids (c) Some components of lipids (d) The parent sugar HO P O O OH Phosphoric acid N Choline CH2CH2OH CH3 CH3 CH3 Glycerol CH2OH CHOH CH2OH CH2 CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3 CH2 CH2 CH2 CH2 CH2 CH2 COO CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH CH C NH2 C C CH HC N N N H N C O C C CH C HN N N H N C O O CH CH C HN N H O CH CH C N N H C O O CH C C HN N H H2N CH3 Nitrogenous bases Five-carbon sugars H3 N H3 N H3 N H3 N OC A COO COO COO COO H3 N COO H3 N COO COO A CH3 OH OC A A CH2OH OH OC A A C A H2 OH Alanine Serine Aspartate OC A A C A SH H2 OH Cysteine Histidine C A OC A OH H2 OH Tyrosine OC A A C A H2 OH C H CH HC N NH (a) Some of the amino acids of proteins FIGURE 1–10 The organic compounds from which most cellular materials are constructed: the ABCs of biochemistry. Shown here are (a) six of the 20 amino acids from which all proteins are built (the side chains are shaded pink); (b) the five nitrogenous bases, two fivecarbon sugars, and phosphoric acid from which all nucleic acids are built; (c) five components of membrane lipids; and (d) D-glucose, the parent sugar from which most carbohydrates are derived. Note that phosphoric acid is a component of both nucleic acids and membrane lipids. 8885d_c01_010 1/15/04 3:28 PM Page 10 mac76 mac76:385_reb:
1.1 Level 2: Level 1 romolecules Monomeric ur DNA Chromosome Amin Protel Plasma membrane Cellulose Cell wall FIGURE 1-11 Structural hierarchy in the molecular organization of mosomes consist of macromolecules of DNA and many different pro ells. In this plant cell, the nucleus is an organelle containing several teins. Each type of macromolecule is made up of simple subunits- ng DNA of nucleotides(deoxyribonucleotides), for with the light microscope. Figure 1-11 illustrates the enzymes are commonly done at very low enzyme con structural hierarchy in cellular organization. centrations in thoroughly stirred aqueous solutions. In The monomeric subunits in proteins, nucleic acid the cell, an enzyme is dissolved or suspended in a gel and polysaccharides are joined by covalent bonds. In ke cytosol with thousands of other proteins, supramolecular complexes, however, macromolecules Thich bind to that enzyme and influence its activity are held together by noncovalent interactions--much weaker, individually, than covalent bonds. Among these noncovalent interactions are hydrogen bonds (between polar groups), ionic interactions(between charged TABLE 1-1 Strengths of Bonds Common groups), hydrophobic interactions (among nonpolar in Biomolecules groups in aqueous solution), and van der Waals inter actions--all of which have energies substantially smaller Bond Bond than those of covalent bonds (Table 1-1). The nature dissociation dissociation of these noncovalent interactions is described in Chap- type energy lype ter 2. The large numbers of weak interactions between of bond (k/mol) of bond(k/mol) macromolecules in supramolecular complexes stablize these assemblies, producing their unique structures Double bonds 0—H C=0 712 In Vitro Studies May Overlook Important Interactions H—H 435 615 419 611 among Molecules 502 One approach to understanding a biological process is N—H to study purified molecules in vitro("in glass"-in the Triple bonds test tube), without interference from other molecules 348 C≡c 816 present in the intact cell-that is, in vivo (in the liv ng"). Although this approach has been remarkably C—N vealing, we must keep in mind that the inside of a cell C—S is quite different from the inside of a test tube. The"in terfering"components eliminated by purification may S-S 214 be critical to the biological function or regulation of the molecule purified. For example, in vitro studies of pure The greater the energy required for bond dissociation( breakage), the stronger the bond
with the light microscope. Figure 1–11 illustrates the structural hierarchy in cellular organization. The monomeric subunits in proteins, nucleic acids, and polysaccharides are joined by covalent bonds. In supramolecular complexes, however, macromolecules are held together by noncovalent interactions—much weaker, individually, than covalent bonds. Among these noncovalent interactions are hydrogen bonds (between polar groups), ionic interactions (between charged groups), hydrophobic interactions (among nonpolar groups in aqueous solution), and van der Waals interactions—all of which have energies substantially smaller than those of covalent bonds (Table 1–1). The nature of these noncovalent interactions is described in Chapter 2. The large numbers of weak interactions between macromolecules in supramolecular complexes stabilize these assemblies, producing their unique structures. In Vitro Studies May Overlook Important Interactions among Molecules One approach to understanding a biological process is to study purified molecules in vitro (“in glass”—in the test tube), without interference from other molecules present in the intact cell—that is, in vivo (“in the living”). Although this approach has been remarkably revealing, we must keep in mind that the inside of a cell is quite different from the inside of a test tube. The “interfering” components eliminated by purification may be critical to the biological function or regulation of the molecule purified. For example, in vitro studies of pure 1.1 Cellular Foundations 11 Level 4: The cell and its organelles Level 3: Supramolecular complexes Level 2: Macromolecules Level 1: Monomeric units Nucleotides Amino acids Protein Cellulose Plasma membrane Chromosome Cell wall Sugars DNA O P O O O O CH2 NH2 H H N N H OH H H O H H3N COO C CH3 H O H OH CH2OH H HO OH OH H O CH2OH H FIGURE 1–11 Structural hierarchy in the molecular organization of cells. In this plant cell, the nucleus is an organelle containing several types of supramolecular complexes, including chromosomes. Chromosomes consist of macromolecules of DNA and many different proteins. Each type of macromolecule is made up of simple subunits— DNA of nucleotides (deoxyribonucleotides), for example. *The greater the energy required for bond dissociation (breakage), the stronger the bond. TABLE 1–1 Strengths of Bonds Common in Biomolecules Bond Bond dissociation dissociation Type energy* Type energy of bond (kJ/mol) of bond (kJ/mol) Single bonds Double bonds OOH 470 CPO 712 HOH 435 CPN 615 POO 419 CPC 611 COH 414 PPO 502 NOH 389 COO 352 Triple bonds COC 348 CmC 816 SOH 339 NmN 930 CON 293 COS 260 NOO 222 SOS 214 enzymes are commonly done at very low enzyme concentrations in thoroughly stirred aqueous solutions. In the cell, an enzyme is dissolved or suspended in a gellike cytosol with thousands of other proteins, some of which bind to that enzyme and influence its activity. 8885d_c01_011 12/20/03 7:04 AM Page 11 mac76 mac76:385_reb: