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2 Chapter 1 Chemical Composition of Living Cells

Overview

, , , , sulfur, and phosphorus normally makeup more than 99% of the mass of living cells. • Ninety-nine percent of the inside living cells are molecules. • Cells normally contain more than DNA. • Homogenous are noninformational. • All non-essential can be generated from acetyl-CoA. • Like certain amino acids and unsaturated fatty acids, various inorganic elements are dietarily "essential". • Most all diseases in animals are manifestations of abnormalities in biomolecules, chemical reactions, or biochemical pathways.

All living , from microbes to mam- between cells (e.g., erythrocyte, liver, muscle mals, are composed of chemical substances or ), they all generally contain a greater from both the inorganic and organic world, that variety of than any other type of appear in roughly the same proportions, and , with about 50% of the solid perform the same general tasks. Hydrogen, matter of the cell being protein (15% on a wet- oxygen, nitrogen, carbon, phosphorus, and weight basis). Cells generally contain many sulfur normally make up more than 99% of the more protein molecules than DNA molecules, mass of living cells, and when combined in yet DNA is typically the largest biomolecule in various ways, form virtually all known organic the cell. About 99% of cellular molecules are biomolecules. They are initially utilized in the water molecules, with water normally synthesis of a small number of building blocks accounting for approximately 70% of the total that are, in turn, used in the construction of a wet-weight of the cell. Although water is vast array of vital (Fig 1-1). obviously important to the vitality of all living There are four general classes of macromol- cells, the bulk of our attention is usually ecules within living cells: nucleic acids, focused on the other 1% of biomolecules. proteins, , and lipids. These Data in Table 1-1 regarding the chemical compounds, which have molecular weights composition of the unicellular Escherichia coli ranging from 1 x 103 to 1 x 106, are created (E. coli), are not greatly different for multicel- through of building blocks that lular organisms, including mammals. Each E. have molecular weights in the range of 50 to coli, and similar bacterium, contains a single 150. Although subtle differences do exist chromosome, therefore, it has only one unique

14 and Protein 3

Formation of Macromolecules Within Cells

Hydrogen, Oxygen, Nitrogen, Carbon, Phosphorus, Sulfur

O

-OPO CH2OH O- CH O 2 O B O OH HO OH O H2NCHCOH H C C S CoA OH R OH 3 Amino acids Simple Sugars Acetyl CoA (e.g. )

CH3(CH2)14COOH B1 B2 B3 B4 (Palmitic Acid)

R1 R2 R3 R4 LIPIDS NUCLEIC ACIDS PROTEINS

CH B = N-Containing Base 3 H R = Side Chain HC CH2 CH2 CH2 CCH3

CH3 CH3 POLYSACCHARIDES

CH3

() HO Figure 1-1

DNA . Mammals, however, contain contain genes (from the Greek word gennan, more chromosomes, and thus have different meaning "to produce"). A chromosome is a DNA molecules in the nucleus. deoxyribonucleic acid (DNA) molecule, and genes are segments of intact DNA. The total number of genes in any given mammalian cell Nucleic Acids may total several thousand. When a cell repli- Nucleic acids are polymers (from cates itself, identical copies of DNA molecules the Greek word poly, meaning "several", and are produced, therefore the hereditary line of mer, meaning "unit"), that store and transmit descent is conserved, and the genetic informa- genetic information. Only 4 different nucleotides tion carried on DNA is available to direct the are used in biosynthesis. Genetic occurrence of virtually all chemical reactions information contained in nucleic acids is within the cell. The bulk of genetic information stored and replicated in chromosomes, which carried on DNA provides instructions for the

4 Chemical Composition of Living Cells

Table 1-1 Approximate Chemical Composition of a Rapidly Dividing Cell (E. coli) Different Kinds of Material % Total Wet Wt. Molecules/Cell Water 70 1 Nucleic acids DNA 1 1 RNA 6 Ribosomal 3 Transfer 40 Messenger 1000 Nucleotides and 0.8 200 Proteins 15 2000-3000 Amino acids and metabolites 0.8 100 Polysaccharides 3 200 ( and metabolites) Lipids and metabolites 2 50 Inorganic ions 1 20 (Major minerals and trace elements) Others 0.4 200 100

Data from Watson JD: Molecular of the Gene, 2nd ed., Philadelphia, PA: Saunders, 1972.

assembly of virtually every protein molecule about half are formed as metabolic intermedi- within the cell. The flow of information from ates, while the remainder must be provided nucleic acids to protein is commonly repre- through the diet. The latter group is referred to sented as DNA —> messenger ribonucleic as "essential" amino acids (see Chapter 3). acid (mRNA) —> transfer RNA (tRNA) —> Each protein formed in the body, unique in its ribosomal RNA (rRNA) —> protein, which own structure and , participates in indicates that the nucleotide sequence in a processes that characterize the individuality of gene of DNA specifies the assembly of a cells, tissues, organs, and systems. A nucleotide sequence in an mRNA molecule, typical cell contains thousands of different which in turn directs the assembly of the amino proteins, each with a different function, and acid sequence in protein through a tRNA and many serve as that catalyze (or rRNA molecules. speed) reactions. Virtually every reaction in a living cell requires an . Other proteins Proteins transport different compounds either outside Proteins are amino acid polymers respon- or inside cells {e.g., lipoproteins and transferrin sible for implementing instructions contained (an iron-binding protein) in plasma, or bilirubin- within the . Twenty different binding proteins in liver cells}; some act as amino acids are used to synthesize proteins, storage proteins (e.g., binds and

14 Amino Acid and Protein Metabolism 5 stores O2 in muscle cells); others as defense precursors to other important biomolecules proteins in blood or on the surface of cells (fatty acids), insulation barriers (neutral fat (e.g., clotting proteins and immunoglobulins); stores), protective coatings to prevent infection others as contractile proteins (e.g., the actin, and excessive gain or loss of water, and some myosin and troponin of skeletal muscle fibers); (A, D, E, and K) and (steroid and others are merely structural in nature (e.g., hormones). Major classes of lipids are the collagen and elastin). Proteins, unlike saturated and unsaturated fatty acids (short, and , are usually not synthesized medium, and long-chain), , and stored as nonfunctional entities. lipoproteins {i.e., chylomicrons (CMs), very low density (VLDL), low density (LDL), intermediate density (IDL), and high density lipoproteins Polysaccharides (HDL)}, and , steroids Polysaccharides are polymers of simple (cholesterol, progesterone, etc.), and sugars (i.e., ). (The term eicosanoids (, thromboxanes, saccharide is derived from the Greek word and leukotrienes). All lipids can be synthesized sakchar, meaning "sugar or sweetness".) Some from acetyl-CoA, which in turn can be generated polysaccharides are homogeneous polymers from numerous different sources, including that contain only one kind of sugar (e.g., carbohydrates, amino acids, short-chain volatile glycogen), while others are complex heteroge- fatty acids (e.g., acetate), bodies, and nous polymers that contain 8-10 types of fatty acids. Simple lipids include only those that sugars. In contrast to heterogenous polymers are of fatty acids and an alcohol (e.g., (e.g., proteins, nucleic acids, and some poly- mono-, di- and triglycerides). Compound lipids saccharides), homogenous polymers are include various materials that contain other considered to be "noninformational". Polysac- substances in addition to an alcohol and fatty charides, therefore, can occur as functional acid (e.g., phosphoacylglycerols, sphin- and structural components of cells (e.g., glyco- gomyelins, and cerebrosides), and derived proteins and glycolipids), or merely as nonin- lipids include those that cannot be neatly classi- formational storage forms of energy (e.g., fied into either of the above (e.g., steroids, glycogen). The 8-10 monosaccharides that eicosanoids, and the fat-soluble vitamins). become the building blocks for heterogenous Although the study of physiological polysaccharides can be synthesized from emphasizes organic molecules, the inorganic glucose, or formed from other metabolic inter- elements (sometimes subdivided into macro- mediates (see Chapter 20). minerals, trace elements, and ultra trace elements), are also important (see Chapter 48). Lipids Several are "essential" , and therefore Lipids (from the Greek word lipos, meaning like certain amino acids and unsaturated fatty "fat") are naturally occurring, nonpolar acids, must be supplied in the diet. Inorganic substances that are mostly insoluble in water elements are typically present in cells as ionic (with the exceptions being the short-chain forms, existing as either free ions or complexed volatile fatty acids and ketone bodies), yet with organic molecules. Many "trace elements" soluble in nonpolar solvents (like chloroform are known to be essential for , health, and and ether). They serve as membrane compo- , and have well-established nents (cholesterol, glycolipids and phospho- actions (e.g., cofactors for enzymes, sites for lipids), storage forms of energy (triglycerides), binding of oxygen (in transport), and structural

6 Chemical Composition of Living Cells

components of nonenzymatic macromole- 3. The largest biomolecule in a living cell cules; see Chapters 48-52). Some investigators is usually: have speculated that perhaps all of the a. Glycogen elements on the periodic chart will someday by b. Protein shown to exhibit physiologic roles in mam- c. Cholesterol malian life. d. Deoxyribonucleic acid Because life depends upon chemical e. Triglyceride reactions, and because most all diseases in animals are manifestations of abnormalities in biomolecules, chemical reactions, or biochem- 4. Which one of the following is a largely ical pathways, physiological chemistry has homogenous , and therefore become the language of all basic medical "noninformational"? sciences. A fundamental understanding of this a. mRNA science is therefore needed not only to help illu- b. minate the origin of disease, but also to help c. Protein formulate appropriate . The chapters d. Hydrogen which follow were designed, therefore, to assist e. Glycogen the reader in developing a basic rational approach to the practice of veterinary medicine. 5. Select the FALSE statement below: Questions a. Some inorganic elements are consid- ered to be "essential" nutrients. b. Triglycerides are considered to be 1. The most prevalent compound in a "simple" lipids. living cell is normally: c. Some polysaccharides are complex a. Protein polymers in that they contain several b. Nucleic acid different types of sugars. c. Water d. Virtually every reaction in a living d. cell requires an enzyme. e. e. Only 10 "essential" amino acids are used in the synthesis of proteins. 2. The basic building block for all lipids is: a. Water 6. About 50% of the solid matter in a cell is normally composed of: b. Acetyl-CoA

a. Nucleic acids c. Phosphorus b 6.

b. Protein d. Nucleic acid e 5.

c. e. Arginine e 4.

d. Lipid

e. Inorganic ions d 3.

2. b 2.

1. c 1. Answers