Brewing Beer

Brewers prepare beer by ethanol fermentation of the carbohydrates in cereal grains (seeds) such as barley, carried out by yeast glycolytic enzymes. The carbohydrates, largely polysaccharides, must first be degraded to disaccharides and monosaccharides. In a process called malting, the barley seeds are allowed to germinate until they form the hydrolytic enzymes required to break down their polysaccharides, at which point germination is stopped by controlled heating. The product is malt, which...

Photosynthetic Carbohydrate Synthesis

The synthesis of carbohydrates in animal cells always employs precursors having at least three carbons, all of which are less oxidized than the carbon in CO2. Plants Light-dependent reactions of photosynthesis FIGURE 20-1 Assimilation of CO2 into biomass in plants. The light-driven synthesis of ATP and NADPH, described in Chapter 19, provides energy and reducing power for the fixation of CO2 into trioses, from which all the carbon-containing compounds of the plant cell are synthesized. The...

Biological Membranes And Transport

11.1 The Composition and Architecture of Membranes 370 11.3 Solute Transport across Membranes 389 -Robert Frost, Mending Wall, in North of Boston, 1914 The first cell probably came into being when a membrane formed, enclosing a small volume of aqueous solution and separating it from the rest of the universe. Membranes define the external boundaries of cells and regulate the molecular traffic across that boundary (Fig. 11-1) in eukaryotic cells, they divide the internal space into discrete...

I I I I I I I I I I I I I I I I I I I I I I I

When a template strand pairs with two different complementary strands, a branch is formed at the point where the three complementary strands meet. The branch migrates when base pairing to one of the two complementary strands is broken and replaced with base pairing to the other complementary strand. In the absence of an enzyme to direct it, this process can move the branch spontaneously in either direction. Spontaneous branch migration is blocked wherever one of...

Amino Acid Oxidation And The Production Of Urea

18.1 Metabolic Fates of Amino Groups 657 18.2 Nitrogen Excretion and the Urea Cycle 665 18.3 Pathways of Amino Acid Degradation 671 I chose the study of the synthesis of urea in the liver because it appeared to be a relatively simple problem. -Hans Krebs, article in Perspectives in Biology and Medicine, 1970 We now turn our attention to the amino acids, the final class of biomolecules that, through their oxidative degradation, make a significant contribution to the generation of metabolic...

Triacylglycerol Biosynthesis in Animals Is Regulated by Hormones

In humans, the amount of body fat stays relatively constant over long periods, although there may be minor short-term changes as caloric intake fluctuates. Carbohydrate, fat, or protein consumed in excess of energy needs is stored in the form of triacylglycerols that can be drawn upon for energy, enabling the body to withstand periods of fasting. T Biosynthesis and degradation of triacylglycerols are regulated such that the favored path depends on the metabolic resources and requirements of the...

The Linear Sequence in DNA Encodes Proteins with Three Dimensional Structures

The information in DNA is encoded in its linear (one-dimensional) sequence of deoxyribonucleotide sub-units, but the expression of this information results in FIGURE 1-30 Complementarity between the two strands of DNA. DNA is a linear polymer of covalently joined deoxyribonucleotides, of four types deoxyadenylate (A), deoxyguanylate (G), deoxycytidy-late (C), and deoxythymidylate (T). Each nucleotide, with its unique three-dimensional structure, can associate very specifically but...

The Energy of Oxidations in the Cycle Is Efficiently Conserved

We have now covered one complete turn of the citric acid cycle (Fig. 16-13). A two-carbon acetyl group entered the cycle by combining with oxaloacetate. Two carbon atoms emerged from the cycle as CO2 from the oxidation of isocitrate and a-ketoglutarate. The energy released by these oxidations was conserved in the reduction of three NAD+ and one FAD and the produc tion of one ATP or GTP. At the end of the cycle a molecule of oxaloacetate was regenerated. Note that the two carbon atoms appearing...

Few Principles Explain the Catalytic Power and Specificity of Enzymes

The rate enhancements they bring about are in the range of 5 to 17 orders of magnitude (Table 6-5). Enzymes are also very specific, readily discriminating between substrates with quite similar structures. How can these enormous and highly selective rate enhancements be explained What is the source of the energy for the dramatic lowering of the activation energies for specific reactions The answer to these questions has two distinct but interwoven parts. The...

Protein Secondary Structure

The term secondary structure refers to the local conformation of some part of a polypeptide. The discussion of secondary structure most usefully focuses on common regular folding patterns of the polypeptide backbone. A few types of secondary structure are particularly stable and occur widely in proteins. The most prominent are the a helix and 3 conformations described below. Using fundamental chemical principles and a few experimental observations, Pauling and Corey predicted the existence of...

The Structure of Chromosomes

The term chromosome is used to refer to a nucleic acid molecule that is the repository of genetic information in a virus, a bacterium, a eukaryotic cell, or an organelle. It also refers to the densely colored bodies seen in the nuclei of dye-stained eukaryotic cells, as visualized using a light microscope. Chromatin Consists of DNA and Proteins The eukaryotic cell cycle (see Fig. 12-41) produces remarkable changes in the structure of chromosomes (Fig. 24-25). In nondividing eukaryotic cells (in...

The Genetic Code

Three major advances set the stage for our present knowledge of protein biosynthesis. First, in the early 1950s, Paul Zamecnik and his colleagues designed a set of experiments to investigate where in the cell proteins are synthesized. They injected radioactive amino acids into rats and, at different time intervals after the injec tion, removed the liver, homogenized it, fractionated the homogenate by centrifuga-tion, and examined the subcellular fractions for the presence of radioactive...

Nad

FIGURE 19-31 Regulation of the ATP-producing pathways. This diagram shows the interlocking regulation of glycolysis, pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation by the relative concentrations of ATP, ADP, and AMP, and by NADH. High ATP (or low ADP and AMP ) produces low rates of glycolysis, pyruvate oxidation, acetate oxidation via the citric acid cycle, and oxidative phosphorylation. All four pathways are accelerated when the use of ATP and the formation of ADP,...

Box 161 Working In Biochemistry

Synthases and Synthetases Ligases and Lyases Kinases, Phosphatases, and Phosphorylases Yes, the Names Are Confusing Citrate synthase is one of many enzymes that catalyze condensation reactions, yielding a product more chemically complex than its precursors. Synthases catalyze condensation reactions in which no nucleoside triphos-phate (ATP, GTP, and so forth) is required as an energy source. Synthetases catalyze condensations that do use ATP or another nucleoside triphosphate as a source of...

The Relationship between Substrate Concentration and Reaction Rate Can Be Expressed Quantitatively

The curve expressing the relationship between S and V0 (Fig. 6-11) has the same general shape for most enzymes (it approaches a rectangular hyperbola), which can be expressed algebraically by the Michaelis-Menten equation. Michaelis and Menten derived this equation starting from their basic hypothesis that the rate-limiting step in enzymatic reactions is the breakdown of the ES complex to product and free enzyme. The equation is The important terms are S , V0, Vmax, and a constant called the...

Evolutionary Foundations

With the cell, biology discovered its atom To characterize life, it was henceforth essential to study the cell and analyze its structure to single out the common denominators, necessary for the life of every cell alternatively, to identify differences associated with the performance of special functions. -Fran ois Jacob, La logique du vivant une histoire de l'h r dit (The Logic of Life A History of Heredity), 1970 We must, however, acknowledge, as it seems to me, that man with all his noble...

Ch2

FIGURE 15-26 Glycogen phosphorylase of liver as a glucose sensor. Glucose binding to an allosteric site of the phosphorylase a isozyme of liver induces a conformational change that exposes its phosphory-lated Ser residues to the action of phosphorylase a phosphatase 1(PP1). This phosphatase converts phosphorylase a to phosphorylase b, sharply reducing the activity of phosphorylase and slowing glycogen breakdown in response to high blood glucose. Insulin also acts indirectly to stimulate PP1 and...

Rc P87o

Purple bacteria (pheophytin-quinone type) Purple bacteria (pheophytin-quinone type) FIGURE 19-47 Functional modules of photosynthetic machinery in purple bacteria and green sulfur bacteria. (a) In purple bacteria, light energy drives electrons from the reaction center P870 through pheo-phytin (Pheo), a quinone (Q), and the cytochrome bct complex, then through cytochrome c2 back to the reaction center. Electron flow through the cytochrome bct complex causes proton pumping, creating an elec-...

Excess Uric Acid Causes Gout

Long thought, erroneously, to be due to high living, gout is a disease of the joints caused by an elevated concentration of uric acid in the blood and tissues. The joints become inflamed, painful, and arthritic, owing to the abnormal deposition of sodium urate crystals. The kidneys are also affected, as excess uric acid is deposited in the kidney tubules. Gout occurs predominantly in males. Its precise cause is not known, but it often involves an underexcretion of urate. A genetic deficiency of...

Diet Regulates the Expression of Genes Central to Maintaining Body Mass

Proteins in a family of ligand-activated transcription factors, the peroxisome proliferator-activated receptors (PPARs), respond to changes in dietary lipid by altering the expression of genes involved in fat and carbohydrate metabolism. These transcription factors were first recognized for their roles in peroxisome synthesis thus their name. Their normal ligands are fatty acids or fatty acid derivatives, but they can also bind synthetic agonists and can be activated in the laboratory by...

Box 191 The World Of Biochemistry

Hot, Stinking Plants and Alternative Respiratory Pathways Many flowering plants attract insect pollinators by releasing odorant molecules that mimic an insect's natural food sources or potential egg-laying sites. Plants pollinated by flies or beetles that normally feed on or lay their eggs in dung or carrion sometimes use foul-smelling compounds to attract these insects. One family of stinking plants is the Araceae, which includes philodendrons, arum lilies, and skunk cabbages. These plants...

DNA Replication

Long before the structure of DNA was known, scientists wondered at the ability of organisms to create faithful copies of themselves and, later, at the ability of cells to produce many identical copies of large and complex macromolecules. Speculation about these problems centered around the concept of a template, a structure that would allow molecules to be lined up in a specific order and joined, to create a macromolecule with a unique sequence and function. The 1940s brought the revelation...

RNA Catalyzes the Splicing of Introns

The first two, the group I and group II introns, differ in the details of their splicing mechanisms but share one surprising characteristic they are self-splicing no protein enzymes are involved. Group I introns are found in some nuclear, mi-tochondrial, and chloroplast genes coding for rRNAs, mRNAs, and tRNAs. Group II introns are generally found in the primary transcripts of mitochondrial or chloro-plast mRNAs in fungi, algae, and plants. Group I and group...

DNA Recombination

The rearrangement of genetic information within and among DNA molecules encompasses a variety of processes, collectively placed under the heading of genetic recombination. The practical applications of DNA rearrangements in altering the genomes of increasing numbers of organisms are now being explored (Chapter 9). Genetic recombination events fall into at least three general classes. Homologous genetic recombination (also called general recombination) involves genetic exchanges between any two...

Cyclic AMP Acts as a Second Messenger for a Number of Regulatory Molecules

Epinephrine is only one of many hormones, growth factors, and other regulatory molecules that act by changing the intracellular cAMP and thus the activity of PKA (Table 12-4). For example, glucagon binds to its receptors in the plasma membrane of adipocytes, activating (via a Gs protein) adenylyl cyclase. PKA, stimulated by the resulting rise in cAMP , phosphorylates and activates two proteins critical to the conversion of stored fat to fatty acids (perilipin and hormone-sensitive...

Pentose Phosphate Pathway of Glucose Oxidation

TIn most animal tissues, the major catabolic fate of glucose 6-phosphate is glycolytic breakdown to pyruvate, much of which is then oxidized via the citric acid cycle, ultimately leading to the formation of ATP. Glucose 6-phosphate does have other catabolic fates, however, which lead to specialized products needed by the cell. Of particular importance in some tissues is the oxidation of glucose 6-phosphate to pentose phosphates by the pentose phosphate pathway (also called the phosphogluconate...

Principles Of Bioenergetics

13.1 Bioenergetics and Thermodynamics 490 13.2 Phosphoryl Group Transfers and ATP 496 13.3 Biological Oxidation-Reduction Reactions 507 The total energy of the universe is constant the total entropy is continually increasing. Rudolf Clausius, The Mechanical Theory of Heat with Its Applications to the Steam-Engine and to the Physical Properties of Bodies, 1865 (trans. 1867) The isomorphism of entropy and information establishes a link between the two forms of power the power to do and the power...

Pentose Phosphate Pathway of Glucose Oxidation 549

The problem of alcoholic fermentation, of the origin and nature of that mysterious and apparently spontaneous change, which converted the insipid juice of the grape into stimulating wine, seems to have exerted a fascination over the minds of natural philosophers from the very earliest times. -Arthur Harden, Alcoholic Fermentation, 1923 Glucose occupies a central position in the metabolism of plants, animals, and many microorganisms. It is relatively rich in potential energy, and thus a good...

The Covalent Structure of Proteins

Purification of a protein is usually only a prelude to a detailed biochemical dissection of its structure and function. What is it that makes one protein an enzyme, another a hormone, another a structural protein, and still another an antibody How do they differ chemically The most obvious distinctions are structural, and these distinctions can be approached at every level of structure defined in Figure 3-16. The differences in primary structure can be especially informative. Each protein has a...

In CAM Plants CO2 Capture and Rubisco Action Are Temporally Separated

Succulent plants such as cactus and pineapple, which are native to very hot, very dry environments, have another variation on photosynthetic CO2 fixation, which reduces loss of water vapor through the pores (stom-ata) by which CO2 and O2 must enter leaf tissue. Instead of separating the initial trapping of CO2 and its fixation by rubisco across space (as do the C4 plants), they separate these two events over time. At night, when the air is cooler and moister, the stomata open to allow entry of...

Box 141 The World Of Biochemistry

Athletes, Alligators, and Coelacanths Glycolysis at Limiting Concentrations of Oxygen Most vertebrates are essentially aerobic organisms they convert glucose to pyruvate by glycolysis, then use molecular oxygen to oxidize the pyruvate completely to CO2 and H2O. Anaerobic catabolism of glucose to lactate occurs during short bursts of extreme muscular activity, for example in a 100 m sprint, during which oxygen cannot be carried to the muscles fast enough to oxidize pyruvate. Instead, the muscles...

Vcm

FIGURE 23-28 Fuel metabolism in the liver during prolonged fasting or in uncontrolled diabetes mellitus. After depletion of stored carbohydrates, to proteins become an important source of glucose, produced from glucogenic amino acids by gluconeogenesis. to Fatty acids imported from adipose tissue are converted to ketone bodies for export to the brain. Broken arrows represent reactions with reduced flux under these conditions. The steps are further described in the text. mobilize...

Figure

Lipid bilayers and viewed as if from the outside of a cell, shows the fine details of the protein's periplas-mic domains (Fig. 2b). And AFM reveals that Fo, the proton-driven rotor of the chloroplast ATP synthase (p. 742), is composed of many subunits (14 in Fig. 2c) arranged in a circle. to dissolve with nonionic detergents they behave like liquid-ordered sphingolipid rafts adrift in a sea of liquid-disordered phospholipids. These lipid rafts are remarkably enriched in two classes of integral...

Adipose Tissue Stores and Supplies Fatty Acids

Adipose tissue, which consists of adipocytes (fat cells) (Fig. 23-16), is amorphous and widely distributed in the body under the skin, around the deep blood vessels, and in the abdominal cavity. It typically makes up about 15 of the mass of a young adult human, with approximately 65 of this mass in the form of triacylglycerols. Adipocytes are metabolically very active, responding quickly to hormonal stimuli in a metabolic interplay with the liver, skeletal muscles, and the heart. Like other...

From an RNA World to a Protein World

Extant ribozymes generally promote one of two types of reactions hydrolytic cleavage of phosphodiester bonds or phosphoryl transfers (Chapter 26). In both cases, the substrates of the reactions are also RNA molecules. The ribosomal RNAs provide an important expansion of the catalytic range of known ribozymes. Coupled to the laboratory exploration of potential RNA catalytic function (see Box 26-3), the idea of an RNA world as a precursor to current life forms becomes increasingly attractive. A...

RNA Synthesis Offers Important Clues to Biochemical Evolution

The extraordinary complexity and order that distinguish living from inanimate systems are key manifestations of fundamental life processes. Maintaining the living state requires that selected chemical transformations occur very rapidly especially those that use environmental energy sources and synthesize elaborate or specialized cellular macromolecules. Life depends on powerful and selective catalysts enzymes and on informational systems capable of both securely storing the blueprint for these...

Box 43 Biochemistry In Medicine

Why Sailors, Explorers, and College Students Should Eat Their Fresh Fruits and Vegetables from this misfortune, together with the unhealthiness of the country, where there never falls a drop of rain, we were stricken with the camp-sickness, which was such that the flesh of our limbs all shrivelled up, and the skin of our legs became all blotched with black, mouldy patches, like an old jack-boot, and proud flesh came upon the gums of those of us who had the sickness, and none escaped from this...

Ieqh Vkea Iekf Iekf Ittv Ittv

The signature, although the sequences of the insertions are quite distinct for the two groups. The variation in the signature sequence reflects the significant evolutionary divergence that has occurred at this site since it first appeared in a common ancestor of both groups. overrepresented, which limits the usefulness of the matrix in identifying homologs that are somewhat distantly related. Tests have shown that the Blosum62 table provides the most reliable alignments over a wide range of...

Stage 1 AminoacyltRNA Synthetases Attach the Correct Amino Acids to Their tRNAs

During the first stage of protein synthesis, taking place in the cytosol, aminoacyl-tRNA synthetases esterify the 20 amino acids to their corresponding tRNAs. Each enzyme is specific for one amino acid and one or more corresponding tRNAs. Most organisms have one aminoacyl-tRNA synthetase for each amino acid. For amino acids with two or more corresponding tRNAs, the same enzyme usually aminoacylates all of them. The structures of all the aminoacyl-tRNA syn-thetases of E. coli have been...

Info

Source Adapted from Reece, R. & Platt, A. (1997) Signaling activation and repression of RNA polymerase II transcription in yeast. Bioessays 19,1001-1010. FIGURE 28-29 Protein complexes involved in transcription activation of a group of related eukaryotic genes. The GAL system illustrates the complexity of this process, but not all these protein complexes are yet known to affect GAL gene transcription. Note that many of the complexes (such as SWI SNF, GCN5-ADA2-ADA3, and mediator) affect the...

Biological Oxidation Reduction Reactions

The transfer of phosphoryl groups is a central feature of metabolism. Equally important is another kind of transfer, electron transfer in oxidation-reduction reactions. These reactions involve the loss of electrons by one chemical species, which is thereby oxidized, and the gain of electrons by another, which is reduced. The flow of electrons in oxidation-reduction reactions is responsible, directly or indirectly, for all work done by living organisms. In nonphotosynthetic organisms, the...

Short Term Eating Behavior Is Set by Ghrelin and PYY336

Ghrelin is a peptide hormone (28 amino acids) produced in cells lining the stomach. It was originally recognized as the stimulus for the release of growth hormone (ghre is the Proto-Indo-European root of grow), then subsequently shown to be a powerful appetite stimulant that works on a shorter time scale (between meals) than leptin and insulin. Ghrelin receptors are located in the pituitary gland (presumably mediating growth hormone release) and in the hypothalamus (affecting appetite), as well...

Glycogen Synthase Is Also Regulated by Phosphorylation and Dephosphorylation

Like glycogen phosphorylase, glycogen synthase can exist in phosphorylated and dephosphorylated forms (Fig. 15-27). Its active form, glycogen synthase a, is un-phosphorylated. Phosphorylation of the hydroxyl side chains of several Ser residues of both subunits converts glycogen synthase a to glycogen synthase b, which is inactive unless its allosteric activator, glucose 6-phosphate, is present. Glycogen synthase is remarkable for its ability to be phosphorylated on various residues by at least...

P

Ouabain and another steroid derivative, digitoxi-genin, are the active ingredients of digitalis, an extract of the leaves of the foxglove plant. (Ouabain is found in lower concentrations in a number of other plants, presumably serving to discourage herbivores.) Digitalis has been used to treat congestive heart failure since its introduction for that purpose (treatment of dropsy) by the British physician William Withering in 1785. It strengthens heart muscle contractions without increasing the...

An Overview Glycolysis Has Two Phases

The breakdown of the six-carbon glucose into two molecules of the three-carbon pyruvate occurs in ten steps, the first five of which constitute the preparatory phase (Fig. 14-2a). In these reactions, glucose is first phos-phorylated at the hydroxyl group on C-6 (step d). The d-glucose 6-phosphate thus formed is converted to d-fructose 6-phosphate (step ), which is again phos-phorylated, this time at C-1, to yield d-fructose 1,6-bisphosphate (step ). For both phosphorylations, ATP is the...

The Response Coefficient Expresses the Effect of an Outside Controller on Flux through a Pathway

We can also derive a quantitative expression for the relative impact of an outside factor (such as a hormone or growth factor), which is neither a metabolite nor an en zyme in the pathway, on the flux through the pathway. The experiment would measure the flux through the pathway (glycolysis, in this case) at various levels of the parameter P (the insulin concentration, for example) to obtain the response coefficient, R, which expresses the change in pathway flux when P ( insulin ) changes. The...

Regulation Of Gene Expression

28.1 Principles of Gene Regulation 1082 28.2 Regulation of Gene Expression in Prokaryotes 1092 28.3 Regulation of Gene Expression in Eukaryotes 1102 The fundamental problem of chemical physiology and of embryology is to understand why tissue cells do not all express, all the time, all the potentialities inherent in their genome. -Fran ois Jacob and Jacques Monod, article in Journal of Molecular Biology, 1961 Of the 4,000 or so genes in the typical bacterial genome, or the perhaps 35,000 genes...

Plastids Are Organelles Unique to Plant Cells and Algae

Most of the biosynthetic activities in plants (including CO2 assimilation) occur in plastids, a family of self-reproducing organelles bounded by a double membrane and containing a small genome that encodes some of their proteins. Most proteins destined for plastids are encoded in nuclear genes, which are transcribed and translated like other nuclear genes then the proteins are imported into plastids. Plastids reproduce by binary fission, replicating their genome (a single circular DNA molecule)...

The Leptin System May Have Evolved to Regulate the Starvation Response

Although much of the initial interest in leptin resulted from its possible role in preventing obesity, the leptin system probably evolved to adjust an animal's activity and metabolism during periods of fasting and starvation, not to restrict weight. The reduction in leptin level triggered by nutritional deficiency reverses the thermo-genic processes illustrated in Figure 23-32, allowing fuel conservation. Leptin activates AMP-dependent protein kinase (AMPK), which regulates many aspects of fuel...

Fatty Acid Biosynthesis Is Tightly Regulated

When a cell or organism has more than enough metabolic fuel to meet its energy needs, the excess is generally converted to fatty acids and stored as lipids such as triacylglycerols. The reaction catalyzed by acetyl-CoA FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol. The mitochondrial outer membrane is freely permeable to all these compounds. Pyruvate derived from amino acid catabolism in the mitochondrial matrix, or from glucose by glycolysis in the cytosol,...

Working with Proteins

Our understanding of protein structure and function has been derived from the study of many individual proteins. To study a protein in detail, the researcher must be able to separate it from other proteins and must have the techniques to determine its properties. The necessary methods come from protein chemistry, a discipline as old as biochemistry itself and one that retains a central position in biochemical research. Proteins Can Be Separated and Purified A pure preparation is essential...

In Substrate Channeling Intermediates Never Leave the Enzyme Surface

Figure 16-6 shows schematically how the pyruvate de-hydrogenase complex carries out the five consecutive reactions in the decarboxylation and dehydrogenation of pyruvate. Step Q) is essentially identical to the reaction catalyzed by pyruvate decarboxylase (see Fig. 14-13c) C-1 of pyruvate is released as CO2, and C-2, which in pyruvate has the oxidation state of an aldehyde, is attached to TPP as a hydroxyethyl group. This first step is the slowest and therefore limits the rate of the overall...

Biochemistry on the Internet

Protein Modeling on the Internet A group of patients suffering from Crohn's disease (an inflammatory bowel disease) underwent biopsies of their intestinal mucosa in an attempt to identify the causative agent. A protein was identified that was expressed at higher levels in patients with Crohn's disease than in patients with an unrelated inflammatory bowel disease or in unaffected controls. The protein was isolated and the following partial amino acid sequence was obtained (reads left to...

Difference Between Sphingomyelin And Phosphatidylcholine By Chemical Test

FIGURE 10-24 Determination of the structure of a fatty acid by mass spectrometry. The fatty acid is first converted to a derivative that minimizes migration of the double bonds when the molecule is fragmented by electron bombardment. The derivative shown here is a picolinyl ester of linoleic acid 18 2(A9,12) (Mr 371) in which the alcohol is picolinol (red). When bombarded with a stream of electrons, this molecule is volatilized and converted to a parent ion (M+ Mr 371), in which the N atom...

Problems

RNA Polymerase (a) How long would it take for the E. coli RNA polymerase to synthesize the primary transcript for the E. coli genes encoding the enzymes for lactose metabolism (the 5,300 bp lac operon, considered in Chapter 28) (b) How far along the DNA would the transcription bubble formed by RNA polymerase move in 10 seconds 2. Error Correction by RNA Polymerases DNA poly-merases are capable of editing and error correction, whereas the capacity for error correction in RNA polymerases appears...

In C4 Plants CO2 Fixation and Rubisco Activity Are Spatially Separated

In many plants that grow in the tropics (and in temperate-zone crop plants native to the tropics, such as maize, sugarcane, and sorghum) a mechanism has evolved to circumvent the problem of wasteful photorespiration. The step in which CO2 is fixed into a three-carbon product, 3-phosphoglycerate, is preceded by several steps, one of which is temporary fixation of CO2 into a four-carbon compound. Plants that use this process are referred to as C4 plants, and the assimilation process as C4...

Ch3 H3c Ch3

Chlorophyll Special Pair Image

FIGURE 19-40 Primary and secondary photopigments. (a) Chlorophylls a and b and bacteriochlorophyll are the primary gatherers of light energy. (b) Phycoerythrobilin and phycocyanobilin (phycobilins) are the antenna pigments in cyanobacteria and red algae. (c) - Carotene (a carotenoid) and (d) lutein (a xanthophyll) are accessory pigments in plants. The areas shaded pink are the conjugated systems (alternating single and double bonds) that largely account for the absorption of visible light....

Control of Body Mass

Auwerx, J. & Staels, B. (1998) Leptin. Lancet 351, 737-742. Brief overview of the leptin system and JAK-STAT signal transductions. Elmquist, J.K., Maratos-Flier, E., Saper, C.B., & Flier, J.S. (1998) Unraveling the central nervous system pathways underlying responses to leptin. Nat. Neurosci. 1, 445-450. Short, excellent review. Flier, J.S. & Maratos-Flier, E. (1998) Obesity and the hypothalamus novel peptides for new pathways. Cell 92, 437-440. Freake, H.C. (1998) Uncoupling proteins...

Hormones Diverse Structures for Diverse Functions

Virtually every process in a complex organism is regulated by one or more hormones maintenance of blood pressure, blood volume, and electrolyte balance embryogenesis sexual differentiation, development, and reproduction hunger, eating behavior, digestion, and fuel allocation to name but a few. We examine here the methods for detecting and measuring hormones and their interaction with receptors, and consider a representative selection of hormone types. The coordination of metabolism in mammals...

Relief Is in the Active Site Cyclooxygenase Isozymes and the Search for a Better Aspirin

Each year, several thousand tons of aspirin (acetyl-salicylate) are consumed around the world for the relief of headaches, sore muscles, inflamed joints, and fever. Because aspirin inhibits platelet aggregation and blood clotting, it is also used in low doses to treat patients at risk of heart attacks. The medicinal properties of the compounds known as salicylates, including aspirin, were first described by western science in 1763, when Edmund Stone of England noted that bark of the willow tree...

Box 44 Working In Biochemistry

Methods for Determining the Three-Dimensional Structure of a Protein The spacing of atoms in a crystal lattice can be determined by measuring the locations and intensities of spots produced on photographic film by a beam of x rays of given wavelength, after the beam has been diffracted by the electrons of the atoms. For example, x-ray analysis of sodium chloride crystals shows that Na+ and Cl ions are arranged in a simple cubic lattice. The spacing of the different kinds of atoms in complex...

Purine and Pyrimidine Bases Are Recycled by Salvage Pathways

Free purine and pyrimidine bases are constantly released in cells during the metabolic degradation of nu-cleotides. Free purines are in large part salvaged and reused to make nucleotides, in a pathway much simpler than the de novo synthesis of purine nucleotides described earlier. One of the primary salvage pathways consists of a single reaction catalyzed by adenosine phosphoribosyltransferase, in which free adenine reacts with PRPP to yield the corresponding adenine nucleotide Free guanine and...

Hormonal Regulation of Fuel Metabolism

The minute-by-minute adjustments that keep the blood glucose level near 4.5 mM involve the combined actions of insulin, glucagon, epinephrine, and cortisol on metabolic processes in many body tissues, but especially in liver, muscle, and adipose tissue. Insulin signals these tissues that blood glucose is higher than necessary as a result, cells take up excess glucose from the blood and convert it to the storage compounds glycogen and tria-cylglycerol. Glucagon signals that blood glucose is too...

Leptin Triggers a Signaling Cascade That Regulates Gene Expression

The leptin signal is transduced by a mechanism also used by receptors for interferon and growth factors, the JAK-STAT system (Fig. 23-34 see Fig. 12-9). The lep-tin receptor, which has a single transmembrane segment, dimerizes when leptin binds to the extracellular domain of two monomers. Both monomers are phos-phorylated on a Tyr residue of the intracellular domain by a Janus kinase (JAK). The -Tyr residues become docking sites for three proteins that are signal transducers and activators of...

Antibodies Have Two Identical Antigen Binding Sites

Immunoglobulin G (IgG) is the major class of antibody molecule and one of the most abundant proteins in the blood serum. IgG has four polypeptide chains two large ones, called heavy chains, and two light chains, linked by noncovalent and disulfide bonds into a complex of Mr 150,000. The heavy chains of an IgG molecule interact at one end, then branch to interact separately with the light chains, forming a Y-shaped molecule (Fig. 5-23). At the hinges separating the base of an IgG molecule from...

The Immune Response Features a Specialized Array of Cells and Proteins

Immunity is brought about by a variety of leukocytes (white blood cells), including macrophages and lymphocytes, all developing from undifferentiated stem cells in the bone marrow. Leukocytes can leave the bloodstream and patrol the tissues, each cell producing one or more proteins capable of recognizing and binding to molecules that might signal an infection. The immune response consists of two complementary systems, the humoral and cellular immune systems. The humoral immune system (Latin...

Glycogen Synthase Kinase 3 Mediates the Actions of Insulin

As we saw in Chapter 12, one way in which insulin triggers intracellular changes is by activating a protein ki-nase (protein kinase B, or PKB) that in turn phosphor-ylates and inactivates GSK3 (Fig. 15-29 see also Fig. 12-8). Phosphorylation of a Ser residue near the amino terminus of GSK3 converts that region of the protein to a pseudosubstrate, which folds into the site at which the priming phosphorylated Ser residue normally binds (Fig. 15-28b). This prevents GSK3 from binding the priming...

Carbohydrate and Lipid Metabolism Are Integrated by Hormonal and Allosteric Mechanisms

As complex as the regulation of carbohydrate metabolism is, it is far from the whole story of fuel metabolism. The metabolism of fats and fatty acids is very closely tied to that of carbohydrates. Hormonal signals such as insulin and changes in diet or exercise are equally important in regulating fat metabolism and integrating it with that of carbohydrates. We shall return to this overall metabolic integration in mammals in Chapter 23, FIGURE 15-32 Difference in the regulation of carbohydrate...

The Discovery and Purification of Hormones Requires a Bioassay

How is a hormone discovered and isolated First, researchers find that a physiological process in one tissue depends on a signal that originates in another tissue. Insulin, for example, was first recognized as a substance that is produced in the pancreas and affects the volume and composition of urine (Box 23-1). Once a physiological effect of the putative hormone is discovered, a quantitative bioassay for the hormone can be developed. In the case of insulin, the assay consisted of injecting...

Box 213 Biochemistry In Medicine

ApoE Alleles Predict Incidence of Alzheimer's Disease In the human population there are three common variants, or alleles, of the gene encoding apolipoprotein E. The most common, accounting for about 78 of human apoE alleles, is APOE3 alleles APOE4 and APOE2 account for 15 and 7 , respectively. The APOE4 allele is particularly common in humans with Alzheimer's disease, and the link is highly predictive. Individuals who inherit APOE4 have an increased risk of late-onset Alzheimer's disease....

How Is a Hormone Discovered The Arduous Path to Purified Insulin

Millions of people with type I (insulin-dependent) diabetes mellitus inject themselves daily with pure insulin to compensate for the lack of production of this critical hormone by their own pancreatic 3 cells. Insulin injection is not a cure for diabetes, but it allows people who otherwise would have died young to lead long and productive lives. The discovery of insulin, which began with an accidental observation, illustrates the combination of serendipity and careful experimentation that led...

Box 112 Biochemistry In Medicine

Defective Glucose and Water Transport in Two Forms of Diabetes When ingestion of a carbohydrate-rich meal causes blood glucose to exceed the usual concentration between meals (about 5 mM), excess glucose is taken up by the myocytes of cardiac and skeletal muscle (which store it as glycogen) and by adipocytes (which convert it to triacylglycerols). Glucose uptake into myocytes and adipocytes is mediated by the glucose transporter GLUT4. Between meals, some GLUT4 is present in the plasma...

Analysis of Metabolic Control 591

Formation of liver glycogen from lactic acid is thus seen to establish an important connection between the metabolism of the muscle and that of the liver. Muscle glycogen becomes available as blood sugar through the intervention of the liver, and blood sugar in turn is converted into muscle glycogen. There exists therefore a complete cycle of the glucose molecule in the body . . . Epinephrine was found to accelerate this cycle in the direction of muscle glycogen to liver glycogen Insulin, on...

Some Homopolysaccharides Serve Structural Roles

Cellulose, a fibrous, tough, water-insoluble substance, is found in the cell walls of plants, particularly in stalks, stems, trunks, and all the woody portions of the plant body. Cellulose constitutes much of the mass of wood, and cotton is almost pure cellulose. Like amylose and the main chains of amylopectin and glycogen, the cellulose molecule is a linear, unbranched homopolysac-charide, consisting of 10,000 to 15,000 d-glucose units. But there is a very important difference in cellulose the...

Key Terms

Terms in bold are defined in the glossary. hydrogen bond 48 bond energy 48 hydrophilic 50 hydrophobic 50 amphipathic 52 micelle 53 van der Waals interactions 54 osmolality 56 isotonic 57 hypertonic 57 hypotonic 57 equilibrium constant (Keq) 60 ion product of water (Kw) 61 pH 61 conjugate acid-base pair 63 dissociation constant (Ka) 63 equation 66 condensation 69 hydrolysis 69

Epinephrine Signals Impending Activity

When an animal is confronted with a stressful situation that requires increased activity fighting or fleeing, in the extreme case neuronal signals from the brain trigger the release of epinephrine and norepinephrine from the adrenal medulla. Both hormones dilate the respiratory passages to facilitate the uptake of O2, increase the rate and strength of the heartbeat, and raise the blood pressure, thereby promoting the flow of O2 and fuels to the tissues (Table 23-6). Epinephrine acts primarily...

Many Chemotherapeutic Agents Target Enzymes in the Nucleotide Biosynthetic Pathways

The growth of cancer cells is not controlled in the same way as cell growth in most normal tissues. Cancer cells have greater requirements for nucleotides as precursors of DNA and RNA, and consequently are generally more sensitive than normal cells to inhibitors of nucleotide biosynthesis. A growing array of important chemotherapeutic agents for cancer and other diseases act by inhibiting one or more enzymes in these pathways. We describe here several well-studied examples that illustrate...

Ch3

Stimulation of glyceroneogenesis leads to an increase in the synthesis of triacylglycerol molecules in the liver and their release into the blood. At the same time, glucocorticoids suppress the expression of the gene encoding PEP carboxykinase in adipose tissue. This results in a decrease in glyceroneogenesis in adipose tissue recycling of fatty acids declines as a result, and more free fatty acids are released into the blood. Thus glyceroneogenesis is regulated reciprocally in the liver and...

The Brain Uses Energy for Transmission of Electrical Impulses

The metabolism of the brain is remarkable in several respects. The neurons of the adult mammalian brain normally use only glucose as fuel (Fig. 23-20). (Astrocytes, the other major cell type in the brain, can oxidize fatty acids.) The brain has a very active respiratory metabolism (Fig. 23-21) it uses O2 at a fairly constant rate, accounting for almost 20 of the total O2 consumed by the body at rest. Because the brain contains very little glycogen, it is constantly dependent on incoming glucose...

The Magic Bullet versus the Bulletproof Vest Penicillin and Lactamase

Because peptidoglycans are unique to bacterial cell walls, with no known homologous structures in mammals, the enzymes responsible for their synthesis are ideal targets for antibiotic action. Antibiotics that hit specific bacterial targets are sometimes called magic bullets. Penicillin and its many synthetic analogs have been used to treat bacterial infections since these drugs came into wide application in World War II. Penicillins and related antibiotics contain the -lactam ring (Fig. 1),...

Tissue Specific Metabolism The Division of Labor

Division Labour Part The Body

Each tissue of the human body has a specialized function, reflected in its anatomy and metabolic activity (Fig. 23-12). Skeletal muscle allows directed motion adipose tissue stores and releases energy in the form of fats, which serve as fuel throughout the body the brain pumps ions across plasma membranes to produce electrical signals. The liver plays a central processing and distributing role in metabolism and furnishes all other organs and tissues with an appropriate mix of nutrients via the...

Hc

FIGURE 22-47 Allopurinol, an inhibitor of xanthine oxidase. Hypoxanthine is the normal substrate of xanthine oxidase. Only a slight alteration in the structure of hypoxanthine (shaded pink) yields the medically effective enzyme inhibitor allopurinol. At the active site, allopurinol is converted to oxypurinol, a strong competitive inhibitor that remains tightly bound to the reduced form of the enzyme. Gertrude Elion (1918-1999) and George Hitchings (1905-1998) Gertrude Elion (1918-1999) and...

Diabetes Mellitus Arises from Defects in Insulin Production or Action

Diabetes mellitus, caused by a deficiency in the secretion or action of insulin, is a relatively common disease nearly 6 of the United States population shows some degree of abnormality in glucose metabolism that is indicative of diabetes or a tendency toward the condition. There are two major clinical classes of diabetes mellitus type I diabetes, or insulin-dependent diabetes mellitus (IDDM), and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called...

The Pancreas Secretes Insulin or Glucagon in Response to Changes in Blood Glucose

Changes Blood Glucose

When glucose enters the bloodstream from the intestine after a carbohydrate-rich meal, the resulting increase in blood glucose causes increased secretion of insulin (and decreased secretion of glucagon). Insulin release by the pancreas is largely regulated by the level of glucose in the blood supplied to the pancreas. The peptide hormones insulin, glucagon, and somatostatin are produced by clusters of specialized pancreatic cells, the islets of Langerhans (Fig. 23-24). Each cell type of the...

Heteropolysaccharides Of Algal Cell Wall

FIGURE 7-21 The structure of starch (amylose). (a) In the most stable conformation, with adjacent rigid chairs, the polysaccharide chain is curved, rather than linear as in cellulose (see Fig. 7-16). (b) Scale drawing of a segment of amylose. The conformation of (a1n4) linkages in amylose, amylopectin, and glycogen causes these polymers to assume tightly coiled helical structures. These compact structures produce the dense granules of stored starch or glycogen seen in many cells (see Fig....

Nucleotides And Nucleic Acids

8.4 Other Functions of Nucleotides 300 A structure this pretty just had to exist. James Watson, The Double Helix, 1968 Nucleotides have a variety of roles in cellular metabolism. They are the energy currency in metabolic transactions, the essential chemical links in the response of cells to hormones and other extracellular stimuli, and the structural components of an array of enzyme cofactors and metabolic intermediates. And, last but certainly not least, they are the constituents of nucleic...

Wernicke Korsakoff Syndrome Is Exacerbated by a Defect in Transketolase

In humans with Wernicke-Korsakoff syndrome, a mutation in the gene for transketolase results in an enzyme having an affinity for its coenzyme TPP that is one-tenth that of the normal enzyme. Although moderate deficiencies in the vitamin thiamine have little effect on individuals with an unmutated transketolase gene, in those with the altered gene, thiamine deficiency drops the level of TPP below that needed to saturate the enzyme. The lowering of transketolase activity slows the whole pentose...

Hormones Are Chemically Diverse

Mammals have several classes of hormones, distinguishable by their chemical structures and their modes of action (Table 23-1). Peptide, amine, and eicosanoid hormones act from outside the target cell via surface receptors. Steroid, vitamin D, retinoid, and thyroid hormones enter the cell and act through nuclear receptors. Nitric oxide also enters the cell, but activates a cytoso-lic enzyme, guanylyl cyclase (see Fig. 12-10). Hormones can also be classified by the way they get from the point of...

Cftr

Eating shellfish that have fed on Gonyaulax can also be fatal shellfish are not sensitive to saxitoxin, but they concentrate it in their muscles, which become highly poisonous to organisms higher up the food chain. The venom of the black mamba snake contains dendrotoxin, which interferes with voltage-gated K+ channels. Tubocurarine, the active component of curare (used as an arrow poison in the Amazon), and two other toxins from snake venoms, cobrotoxin and...

Box 181 Biochemistry In Medicine

Analyses of certain enzyme activities in blood serum give valuable diagnostic information for a number of disease conditions. Alanine aminotransferase (ALT also called glutamate-pyruvate transaminase, GPT) and aspartate aminotransferase (AST also called glutamate-oxaloacetate transaminase, GOT) are important in the diagnosis of heart and liver damage caused by heart attack, drug toxicity, or infection. After a heart attack, a variety of enzymes, including these aminotransferases, leak from the...

Ch3ch2

Glyceroneogenesis

Pioglitazone (Actos) Thiazolidinediones Pioglitazone (Actos) Thiazolidinediones T FIGURE 21-22 Regulation of glyceroneogenesis. (a) Glucocorticoid hormones stimulate glyceroneogenesis and gluco-neogenesis in the liver, while suppressing glyceroneogenesis in the adipose tissue (by reciprocal regulation of the gene expressing PEP carboxykinase (PEPCK) in the two tissues) this increases the flux through the triacylglycerol cycle. The glycerol freed by the breakdown of triacylglycerol in adipose...

Xlu

FIGURE 26-6 Transcription initiation and elongation by E. coli RNA polymerase. (a) Initiation of transcription requires several steps generally divided into two phases, binding and initiation. In the binding phase, the initial interaction of the RNA polymerase with the promoter leads to formation of a closed complex, in which the promoter DNA is stably bound but not unwound. A 12 to 15 bp region of DNA from within the 10 region to position +2 or +3 is then unwound to form an open complex....

Glucagon Counters Low Blood Glucose

Liver State

Several hours after the intake of dietary carbohydrate, blood glucose levels fall slightly because of the ongoing oxidation of glucose by the brain and other tissues. Lowered blood glucose triggers secretion of glucagon and decreases insulin release (Fig. 23-27). Glucagon causes an increase in blood glucose concentration in several ways (Table 23-4). Like epinephrine, it stimulates the net breakdown of liver glycogen FIGURE 23-26 The well-fed state the lipogenic liver. Immediately after a...

05

Hemoglobin Variants There are almost 500 naturally occurring variants of hemoglobin. Most are the result of a single amino acid substitution in a globin polypep-tide chain. Some variants produce clinical illness, though not all variants have deleterious effects. A brief sample is presented below. HbS (sickle-cell Hb) substitutes a Val for a Glu on the surface Hb Cowtown eliminates an ion pair involved in T-state stabilization Hb Memphis substitutes one uncharged polar residue for another of...

Pka

Phosphorylation of cellular proteins by PKA causes the cellular response to epinephrine. Gs ( a subunit) moves to adenylyl cyclase and activates it. Adenylyl cyclase catalyzes the formation of cAMP. FIGURE 12-12 Transduction of the epinephrine signal the fi-adrenergic pathway. The seven steps of the mechanism that couples binding of epinephrine (E) to its receptor (Rec) with activation of adenylyl cyclase (AC) are discussed further in the text. The same adenylyl cyclase molecule in the plasma...

The Liver Processes and Distributes Nutrients

During digestion in mammals, the three main classes of nutrients (carbohydrates, proteins, and fats) undergo enzymatic hydrolysis into their simple constituents. This breakdown is necessary because the epithelial cells lining the intestinal lumen absorb only relatively small molecules. Many of the fatty acids and monoacylglycerols released by digestion of fats in the intestine are reassembled within these epithelial cells into triacylglyc-erols (TAGs). After being absorbed, most sugars and...

Complementary Interactions between Proteins and Ligands The Immune System and Immunoglobulins

Our discussion of oxygen-binding proteins showed how the conformations of these proteins affect and are affected by the binding of small ligands O2 or CO to the heme group. However, most protein-ligand interactions do not involve a prosthetic group. Instead, the binding site for a ligand is more often like the hemoglobin binding site for BPG a cleft in the protein lined with amino acid residues, arranged to render the binding interaction highly specific. Effective discrimination between ligands...

Solutes Affect the Colligative Properties of Aqueous Solutions

Solutes of all kinds alter certain physical properties of the solvent, water its vapor pressure, boiling point, melting point freezing point , and osmotic pressure. These are called colligative tied together properties, because the effect of solutes on all four properties has the same basis the concentration of water is lower in solutions than in pure water. The effect of solute concentration on the colligative properties of water is independent of the chemical properties of the solute it...

Cellulose Is Synthesized by Supramolecular Structures in the Plasma Membrane

Cellulose Synthase Complex

The complex enzymatic machinery that assembles cellulose chains spans the plasma membrane, with one part positioned to bind the substrate, UDP-glucose, in the cytosol and another part extending to the outside, responsible for elongating and crystallizing cellulose molecules in the extracellular space. Freeze-fracture electron microscopy shows these terminal complexes, also called rosettes, to be composed of six large particles arranged in a regular hexagon Fig. 20-30 . Several proteins,...

Bacterial Signaling Entails Phosphorylation in a Two Component System

E. coli responds to a number of nutrients in its environment, including sugars and amino acids, by swimming toward them, propelled by one or a few flagella. A family of membrane proteins have binding domains on the outside of the plasma membrane to which specific attractants sugars or amino acids bind Fig. 12-26 . Ligand binding causes another domain on the inside of the plasma membrane to phosphorylate itself on a His residue. This first component of the two-component system, the receptor His...