The Structure of Materials
1.5 STRUCTURE OF BIOLOGICS
1.5.1 Review of Biological Molecules
Just as we began our description of polymer structure with an organic chemistry review, let us begin our introduction to biological materials with some simple biochemistry.
1.5.1.1 Amino Acids and Proteins. Proteins are the molecules that perform the functions of life. They can be enzymes that catalyze biological reactions, or they can be the receptor site on a membrane that binds a specific substance. Proteins are important parts of both bones—the so-called hard biologics—and the soft biologics such as muscle and skin. Any discussion of the structure of living organisms must begin with the structure of proteins.
Proteins are composed ofamino acids. As shown in Figure 1.83, an amino acid has a carboxyl group, an amino group (refer to Table 1.22 for a summary of functional
C COOH
R
H2N H
Carboxyl group
α-carbon (carbon 2) Amino group
Variable part (side chain) Figure 1.83 General structure of an amino acid.
STRUCTURE OF BIOLOGICS 115
groups), a central atom identified as the alpha (α) carbon, and a variable part know as the side chain (R). Normally, the amino acid is in its dissociated state, such that the terminal hydrogen on the carboxyl group moves to the amino group, thereby creating a carboxylate group (COO−)and an ammonium group (NH3+)known as azwitterion.
The molecule remains neutral overall, and there may be several stable zwitterion forms, depending on the amino acid. Note also that the α-carbon is an asymmetric carbon, resulting in a chiral molecule for all but one of the naturally occurring amino acids.
All the amino acids are found in only one of the stereoisomer configurations (the
L-configuration).
There are only 20 amino acids that make up proteins (technically, 19 amino acids and one imino acid), differing only in the type of R group they contain (see Table 1.34).
Each amino acid has a specific name and three-letter designation. Most amino acids decompose instead of melting due to the strong intermolecular electrostatic attrac- tions, with decomposition temperatures ranging from 185–315◦C, and they are only sparingly soluble in water, with the exceptions of glycine, alanine, proline, lysine, and arginine.
To form proteins, the carboxylic acid group on one amino acid reacts with the amine group on another molecule in a condensation reaction that forms one water molecule and a –CO–NH–CHR– linkage known as apeptide bond. A molecule containing more than about 100 amino acid sequences is called apolypeptide, and a protein is composed of one (or more) polypeptide chains. Thus, the number of possible proteins from the 20 amino acids is enormous (∼20100). Replacing even one amino acid in the sequence of a protein can change its function completely. Sickle cell anemia is the result of replacing only one valine amino acid with a glutamic acid unit in one protein chain of the hemoglobin molecule. The peptide sequence is named by starting at theN(-amino) terminus of the polypeptide.
As with the polymers we have already described, peptides and proteins can possess complex conformations by rotation of bonds in the backbone and interaction between side chains. The stability of these structures is strongly dependent upon the R groups and, hence, the specific amino acid sequence, as well as the environment in which the protein finds itself. Figure 1.84 illustrates a few of the common conformations found in proteins. The α-helix occurs when the chain coils like a right-hand screw to form a cylinder, and it is the result of hydrogen bonding between the C=O and N–H in adjacent turns of the helix. Only the right-handed α-helix occurs in nature, and its presence results in an electric dipole with excess positive charge at one end and excess negative charge at the other. In theβ-sheet, the peptide chain is much more extended, with 0.35 nm between adjacent peptide groups, in comparison to 0.15 nm for the α- helix. These sheet structures are also the result of hydrogen bonding. Theα-helix and the β-sheet are examples of secondary structure in proteins. Tertiary and quaternary structures also exist, but are beyond the scope of this text. Depending on the nature of the side chains, there can also be hydrophobic interactions within the chain, leading to chain extension. Finally, disulfide bonds can occur when two cysteine residues react to form a covalent –S–S– bond. The breaking of disulfide bonds, or any action that leads to an alteration in the structure of a protein as to render it inactive, leads to denaturation. Denatured proteins also tend to have decreased solubility.
1.5.1.2 DNA and RNA. Like proteins, deoxyribonucleic acid (DNA) and ribonu- cleic acid (RNA) are polymers, but instead of amino acids as repeat units, they are
Table 1.34 Common Amino Acids
NH2
CHCOOH R
Name Abbreviation
NH2
CHCOOH H
Glycine Gly
NH2
CHCOOH CH3
Alanine Ala
NH2 CHCOOH CH3CH
CH3 Valine Val
NH2
CHCOOH CH3CHCH2
CH3 Leucine Leu
NH2
CHCOOH CH3CH2CH
CH3 Isoleucine Ile
NH2
CHCOOH CH3SCH2CH2
Methionine Met
NH CHCOOH CH2
CH2 CH2
Proline Pro
CH2 CHCOOH
NH2 Phenylalanine Phe
CH2 CHCOOH NH2
NH
Tryptophan Trp
NH2
CHCOOH HOCH2
Serine Ser
NH2
CHCOOH CH3CH
OH Threonine Thr
NH2
CHCOOH HSCH2
Cysteine Cys
NH2
CHCOOH CH2
HO
Tyrosine Tyr
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Table 1.34 (continued) NH2
CHCOOH R
Name Abbreviation
NH2
CHCOOH H2NCCH2
O Asparagine Asn
NH2
CHCOOH H2NCCH2CH2
O Glutamine Gln
NH2
CHCOOH HOCCH2
O Aspartic acid Asp
NH2
CHCOOH HOCCH2CH2
O Glutamic acid Glu
NH2
CHCOOH H2NCH2CH2CH2CH2
Lysine Lys
NH2
CHCOOH H2NCNHCH2CH2CH2
NH Arginine Arg
N NH
CH2 CHCOOH
NH2 Histidine His
composed of a chain of nucleotides. Each nucleotide is composed of three basic struc- tural units: a base, asugar, and a phosphate group (see Figure 1.85). One base with its sugar (and without the phosphate group) is called anucleoside. The sugar in RNA is calledribose, which is reduced in DNA by a loss of oxygen at the 2carbon to form deoxyribose (see Figure 1.86). There are only five primary bases found in polynu- cleotides: twopurines represented byadenine (A) andguanine (G); and threepyrim- idinesrepresented bycytosine(C),thymine (T), anduracil(U). Thymine is found only in DNA nucleotides, and uracil only in RNA nucleotides, which results in four DNA nucleotides (see Figure 1.87) and four RNA nucleotides. The four DNA nucleotides are 2-deoxyadenosine monophosphate (dAMP), 2-deoxyguanosine monophosphate (dGMP), 2-deoxycytidine monophosphate (dCMP), and thymidine monophosphate (TMP), the latter of which is already assumed to have 2-deoxyribose as the sugar since it occurs only in DNA and not in RNA.
The nucleic acid polymer is formed when the nucleotides attach to one another through phosphodiester bonds, which connect the 3-OH group of one nucleotide to the 5-OH group of another nucleotide through the phosphate group. The order of the nucleotides in the chain is the primary structure of the DNA or RNA molecule, and it can be represented in short-hand notation with only the base pair designation
Hydrophobic interactions
Sheet structure
Alpha-helix Disulfide bond Side chain
hydrogen bond S
CH2 NH3+
+H3N CH3
CH
−O
COO−
COO−
C O H O CH3
S
Ionic interaction
Figure 1.84 Some common structural elements in a hypothetical protein molecule. Reprinted, by permission, from M. E. Houston,Biochemistry Primer for Exercise Science, 2nd ed., p. 9.
Copyright2001 by Michael E. Houston.
5'
4' 1'
3' phosphate base
sugar O
2'
Figure 1.85 The chemical structure of DNA and RNA nucleotides. From H. R. Matthews, R. Freedland, and R. L. Miesfeld, Biochemistry: A Short Course. Copyright 1997 by John Wiley & Sons, Inc. This material is used by permission of John Wiley & Sons, Inc.
(A,G,C,T, or U). Some sequences are highly repetitive, such as the Alu sequence, which is a sequence of 123 base pairs that occurs millions of times in the chain. Some sequences are specific binding sites for certain proteins, as in the TATAA sequence found near the start of many DNA molecules.
As with proteins, the nucleic acid polymers can denature, and they have secondary structure. In DNA, two nucleic acid polymer chains are twisted together with their bases facing inward to form adouble helix. In doing so, the bases shield their hydrophobic components from the solvent, and they form hydrogen bonds in one of only two specific patterns, called base pairs. Adenine hydrogen bonds only with thymine (or uracil in RNA), and guanine pairs only with cytosine. Essentially every base is part of a base pair in DNA, but only some of the bases in RNA are paired. The double-helix structure
STRUCTURE OF BIOLOGICS 119
Figure 1.86 The chemical structure of the sugars in RNA (ribose) and DNA (deoxyribose).
Reprinted, by permission, from M. E. Houston,Biochemistry Primer for Exercise Science, p. 30, 2nd ed. Copyright2001 by Michael E. Houston.
Figure 1.87 The four DNA nucleotides. Reprinted, by permission, from D. E. Schumm,Essen- tials of Biochemistry, 2nd ed., p. 17. Copyright1995 by Little, Brown and Company, Inc.
formed by DNA is comprised not only of two nucleic acid polymer chains, but the chains have complementary sequences such that when they are wound around each other in an antiparallel fashion, each base is opposite its appropriate partner and a base pair is automatically formed. As with proteins, this double helix is also right-handed, with the phosphate groups on the outside of the structure where they can interact with solvent ions. Thus, there are two “grooves” formed between the phosphate chains (see Figure 1.88): a major groove and a minor groove. The edges of the base pairs are accessible to the solvent in the grooves and provide regions where specific protein binding can occur. The double helix undergoes further conformational changes, called supercoiling, which allows a single molecule of human DNA, which is nearly one meter long if stretched out, to fit into the nucleus of a cell.
DNA is purely a molecular code: The molecule itself executes no function. A specific section of a DNA molecule, known as a gene, is used only as a blueprint
Major groove Minor
groove
Figure 1.88 Major and minor grooves in the DNA double helix. Reprinted, by permission, from D. E. Schumm, Essentials of Biochemistry, 2nd ed., p. 18. Copyright1995 by Little, Brown and Company, Inc.
to produce a nucleic acid chain called messenger RNA (mRNA) that carries out the synthesis of proteins. From a sequence of four bases sequence in DNA, mRNA specifies the correct sequence of the 20 amino acids required to produce a specific protein.
Interestingly, only about 5% of all human DNA is used to produce protein molecules.
Nonetheless, this is still roughly 100,000 gene sequences. There is currently an effort underway to map all of the human genes, called the Human Genome Project, which you can learn more about by visiting their website at the National Institutes of Health:
www.nhgri.nih.gov/.
1.5.1.3 Cells. We finally come to what are the direct building blocks of biological materials:cells. Cells are assemblies of molecules enclosed within aplasma membrane that carry out specific functions. The human body contains over 1014 cells, all of which take in nutrients, oxidize fuels, and excrete waste products. Despite their varied functions, all cells have a similar internal organization. We will concentrate on this internal organization for now and will leave the topics of cell reproduction, energy production, and related concepts to the molecular biologist.
Surrounding the outside of all cells is the plasma membrane (see Figure 1.89). It is composed primarily of lipids and is selectively permeable, limiting the exchange of molecules between the inside and outside of the cell. The outside of the plasma membrane contains all the carbohydrates and receptor sites. The cytoplasm includes everything inside the plasma membrane except for the nucleus. Energy is generated
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Golgi Body
Ribosomes and Polysomes
Nucleolus Nuclear Envelope
Lipid Droplets
Plasma Membrane
Endoplasmic Reticulum (Smooth)
Lysosomes Mitochondrion Glycogen Granules Chromatin Endoplasmic Reticulum (Rough)
Figure 1.89 Diagram of a typical human cell showing some of the subcellular structures.
Reprinted, by permission, from D. E. Schumm,Essentials of Biochemistry, 2nd ed., p. 4. Copy- right1995 by Little, Brown and Company, Inc.
in the cell by themitochondria, where cellular fuel is oxidized. There may be several mitochondria per cell. TheGolgi complex is composed of parallel membrane sacs and is used to secrete proteins. Theendoplasmic reticulum(ER) is a system of membranes that store, segregate, and transport substances within the cell. The ER is continuous with the Golgi complex and the nuclear membrane. The nuclear membrane, or envelope, surrounds the nucleolus, which contains RNA, as well as DNA and other proteins.
Normally, the DNA is a diffuse tangle of fine threads called chromatin. The rest of the cytoplasm is composed of lysosomes which degrade nucleic acids, proteins, and complex carbohydrates; peroxisomes, which contain a variety of oxidation enzymes;
polysomes, which are engaged in protein synthesis using the mRNA; and glycogen, which is a polymer of glucose, used for energy.
Cells with similar structure and function group together to formtissue. Despite the astounding diversity of cell types and functions, there are really only four major types of tissue:epithelial, connective, muscular, andnervous. Epithelial tissues are usually delicate cells that form linings of internal structures and organs. They also form the outer covering of our bodies, calledskin. Connective tissues are found in the walls of organs where they provide structural support.Bone, cartilage, ligaments, andtendons are all types of connective tissue. Muscle tissue enables the body to move, and it is characterized by its ability to contract. Nervous tissue is composed of highly specialized cells called neurons, and it is characterized by its ability to translate stimulation into electrochemical nervous impulses. The region between cells in a tissue is equally important. It is often termed the extracellular matrix, and it contains proteins and ions that perform vital functions. We will see that the extracellular matrix components have a profound effect on how well foreign materials are accepted (or rejected) by the
body. For the time being, however, we will concentrate on the tissue itself by further generalizing biological materials as either “hard” or “soft” materials.