Biochemistry, 4th Edition P110 potx

Hormones and other signal molecules in biological 1056 Chapter 32 The Reception and Transmission of Extracellular Information The Catecholamine Neurotransmitters Are Derived from Tyrosin

been used illegally as a hallucinogenic drug, under the street name of angel dust.

Sadly, it has caused many serious, long-term psychological problems in its users.

␥-Aminobutyric Acid and Glycine Are Inhibitory Neurotransmitters

Certain neurotransmitters, acting through their conjugate postsynaptic receptors,

inhibit the postsynaptic neuron from propagating nerve impulses from other

neu-rons Two such inhibitory neurotransmitters are ␥-aminobutyric acid (GABA) and

glycine. These agents make postsynaptic membranes permeable to chloride ions

and cause a net influx of Cl, which in turn causes hyperpolarization of the

post-synaptic membrane (making the membrane potential more negative)

Hyperpolar-ization of a neuron effectively raises the threshold for the onset of action potentials

in that neuron, making the neuron resistant to stimulation by excitatory

neuro-transmitters These effects are mediated by the GABA and glycine receptors, which

are ligand-gated chloride channels (Figure 32.60) GABA is derived by a

decar-boxylation of glutamate (Figure 32.61) and appears to operate mainly in the brain,

whereas glycine acts primarily in the spinal cord The glycine receptor has a specific

affinity for the convulsive alkaloid strychnine (Figure 32.62) The effects of ethanol

on the brain arise in part from the opening of GABA receptor Clchannels.

FIGURE 32.60 GABA (-aminobutyric acid) and

glycine are inhibitory neurotransmitters that activate chloride channels Influx of Clcauses a hyperpolar-ization of the postsynaptic membrane GABA recep-tors are similar in many respects to nicotinic acetyl-choline receptors, with an 2 stoichiometry.

(a) Top view; (b) side view.(Images courtesy of Donald Weaver, University of Nova Scotia, and Valerie Campagna-Slater, University of Toronto.)

Glutamate

+H3N C CH2

H

CH2 COO–

COO–

+H3N CH2 CH2 CH2 COO–

-Aminobutyrate

(GABA)

C CH2 CH2 COO–

O

H Succinate semialdehyde

–OOC CH2 CH2 COO–

Succinate

Glutamate decarboxylase

GABA-glutamate transaminase

Succinate semialdehyde dehydrogenase

FIGURE 32.61 Glutamate is converted to GABA by glutamate decarboxylase GABA is degraded by the action

of GABA–glutamate transaminase and succinate semialdehyde dehydrogenase to produce succinate

N

O

H

O

N

H H

Strychnine FIGURE 32.62 Glycine receptors are distinguished by their unique affinity for strychnine

1054 Chapter 32 The Reception and Transmission of Extracellular Information

HUMAN BIOCHEMISTRY

The Biochemistry of Neurological Disorders

Defects in catecholamine processing are responsible for the

symp-toms of many neurological disorders, including clinical depression

(which involves norepinephrine [NE]) and parkinsonism

(involv-ing dopamine [DA]) Once these neurotransmitters have bound to

and elicited responses from postsynaptic membranes, they must be

efficiently cleared from the synaptic cleft (see accompanying figure,

part a) Clearing can occur by several mechanisms NE and DA

transport or reuptake proteins exist both in the presynaptic

mem-brane and in nearby glial cell memmem-branes On the other hand,

cat-echolamine neurotransmitters can be metabolized and inactivated

by two enzymes: catechol-O-methyl-transferase in the synaptic cleft

and monoamine oxidase in the mitochondria (see figure, part b).

Catecholamines transported back into the presynaptic neuron are

accumulated in synaptic vesicles by the same H-ATPase/H-ligand

exchange mechanism described for glutamate Clinical depression

has been treated by two different strategies Monoamine oxidase

inhibitors act as antidepressants by increasing levels of

cate-cholamines in the brain Another class of antidepressants, the

tri-cyclics, such as desipramine (see figure, part c), act on several

classes of neurotransmitter reuptake transporters and facilitate

more prolonged stimulation of postsynaptic receptors Prozac is a

more specific reuptake inhibitor and acts only on serotonin reup-take transporters

Parkinsonism is characterized by degeneration of dopaminergic neurons, as well as consequent overproduction of postsynaptic dopamine receptors In recent years, Parkinson’s patients have been

treated with dopamine agonists such as bromocriptine (see figure,

part d) to counter the degeneration of dopamine neurons

Catecholaminergic neurons are involved in many other

interest-ing pharmacological phenomena For example, reserpine (see

fig-ure, part e), an alkaloid from a climbing shrub of India, is a power-ful sedative that depletes the level of brain monoamines by inhibiting the H–monoamine exchange protein in the membranes

of synaptic vesicles

Cocaine(see figure, part f), a highly addictive drug, binds with high affinity and specificity to reuptake transporters for the mono-amine neurotransmitters in presynaptic membranes Thus, at least one of the pharmacological effects of cocaine is to prolong the synaptic effects of these neurotransmitters

Postsynaptic neuron

Norepinephrine

Norepi-nephrine receptor

Receptor Mitochondrion

H +

Presynaptic neuron

Monoamine oxidase

Desipramine

Tranylcypromine

Reserpine

(a)

䊳 (a)The pathway for reuptake and vesicular

repackaging of the catecholamine

neurotransmit-ters The sites of action of desipramine,

tranyl-cypromine, and reserpine are indicated

Catechol-O-methyltransferase

Monoamine oxidase

NH3+

H

H3CO

H

Methyl group donor

OH

CH3

3-O-Methylepinephrine

NH3+

H

HO

H

OH

Norepinephrine

NH4+

HO

H

OH

3,4-Dihydroxyphenylglycolaldehyde

O

H

(b)

NH2

Tranylcypromine

(c)

N

CH2

CH2

CH2 NH

CH3

O CH

CH2

CF3

CH2 NH

CH3.HCl

HN

Br H

H

N

CH3

C

O H N

N O

O HO CH(CH3)2

H CH2CH(CH3)2

O

N H

Bromocriptine (d)

H

N

H

CH3O

H2O

C O

O C OCH3 O

OCH3 OCH3

OCH3

Reserpine

(e)

OCH3

H

N

CH3

Cocaine

O C O C

O

(f)

䊱 (b)Norepinephrine can be degraded in the synaptic cleft by catechol-O-methyltransferase

or in the mitochondria of presynaptic neurons by monoamine oxidase (c) The structures of

tranylcypromine, desipramine, and Prozac (d) The structure of bromocriptine (e) The

struc-ture of reserpine (f) The strucstruc-ture of cocaine.

32.1 What Are Hormones? Many different chemical species act as

hor-mones Steroid hormones, all derived from cholesterol, regulate

metab-olism, salt and water balances, inflammatory processes, and sexual

func-tion Several hormones are amino acid derivatives Among these are

epinephrine and norepinephrine (which regulate smooth muscle

con-traction and relaxation, blood pressure, cardiac rate, and the processes

of lipolysis and glycogenolysis) and the thyroid hormones (which stimu-late metabolism) Peptide hormones are a large group of hormones that appear to regulate processes in all body tissues, including the release of yet other hormones Hormones and other signal molecules in biological

1056 Chapter 32 The Reception and Transmission of Extracellular Information

The Catecholamine Neurotransmitters Are Derived from Tyrosine Epinephrine, norepinephrine, dopamine, andL-dopa are collectively known as the

catecholamine neurotransmitters These compounds are synthesized from tyrosine (Figure 32.63), both in sympathetic neurons and in the adrenal glands They func-tion as neurotransmitters in the brain and as hormones in the circulatory system.

However, these two pools operate independently, thanks to the blood–brain barrier,

which permits only very hydrophobic species in the circulatory system to cross

over into the brain Hydroxylation of tyrosine (by tyrosine hydroxylase) to form

3,4-d ihydroxyphenylalanine (L-dopa) is the rate-limiting step in this pathway Dopa-mine, a crucial catecholamine involved in several neurological diseases, is synthe-sized from L-dopa by a pyridoxal phosphate-dependent enzyme, dopa decarboxy-lase. Subsequent hydroxylation and methylation produce norepinephrine and epinephrine (Figure 32.63) The methyl group in the final reaction is supplied by

S -adenosylmethionine.

Each of these catecholamine neurotransmitters is known to play a unique role in synaptic transmission The neurotransmitter in junctions between sympathetic nerves and smooth muscle is norepinephrine On the other hand, dopamine is in-volved in other processes Either excessive brain production of dopamine or hy-persensitivity of dopamine receptors is responsible for psychotic symptoms and schizophrenia, whereas lowered production of dopamine and the loss of dopamine neurons are important factors in Parkinson’s disease.

Various Peptides Also Act as Neurotransmitters

Many relatively small peptides have been shown to possess neurotransmitter activity (see Table 32.3) One of the challenges of this field is that the known neuropeptides may represent a very small subset of the neuropeptides that exist Another chal-lenge arises from the small in vivo concentrations of these agents and the small number of receptors that are present in neural tissue Physiological roles for most

of these peptides are complex For example, the endorphins and enkephalins are natural opioid substances and potent pain relievers The endothelins are a family of

homologous regulatory peptides, synthesized by certain endothelial and epithelial cells that act on nearby smooth muscle and connective tissue cells They induce or affect smooth muscle contraction; vasoconstriction; heart, lung, and kidney

func-tion; and mitogenesis and tissue remodeling Vasoactive intestinal peptide (VIP)

produces a G protein–adenylyl cyclase–mediated increase in cAMP, which in turn triggers a variety of protein phosphorylation cascades, one of which leads to

con-version of phosphorylase b to phosphorylase a, stimulating glycogenolysis

More-over, VIP has synergistic effects with other neurotransmitters, such as norepineph-rine In addition to increasing cAMP levels through -adrenergic receptors,

norepinephrine acting at 1-adrenergic receptors markedly stimulates the increases

in cAMP elicited by VIP Many other effects have also been observed For example, injection of VIP increases rapid eye movement (REM) sleep and decreases waking time in rats VIP receptors exist in regions of the central nervous system involved in sleep modulation.

Tyrosine

NH3+

H

Dopa

O2

CO2

C COO–

NH3+

H HO

Dopamine

NH3+

H HO

NH3+

H

HO

H

OH

CH3

+H2N

H

HO

H

Methyl group

donor

OH

CH3

Epinephrine (Adrenaline)

Norepinephrine (Noradrenaline)

䊴 FIGURE 32.63 The pathway for the synthesis of catecholamine neurotransmitters Dopa, dopamine, noradren-aline, and adrenaline are synthesized sequentially from tyrosine

Preparing for an exam? Create your own study path for this

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1.Compare and contrast the features and physiological advantages

of each of the major classes of hormones, including the steroid

hormones, polypeptide hormones, and the amino acid–derived

hormones

2.Compare and contrast the features and physiological advantages of

each of the known classes of second messengers

3.Nitric oxide may be merely the first of a new class of gaseous second

messenger/neurotransmitter molecules Based on your knowledge

of the molecular action of nitric oxide, suggest another gaseous

mol-ecule that might act as a second messenger and propose a molecular

function for it

4.Herbimycin A is an antibiotic that inhibits tyrosine kinase activity by

binding to SH groups of cysteine in the src gene tyrosine kinase and

other similar tyrosine kinases What effect might it have on normal

rat kidney cells that have been transformed by Rous sarcoma virus?

Can you think of other effects you might expect for this interesting

antibiotic?

5.Monoclonal antibodies that recognize phosphotyrosine are

com-mercially available How could such an antibody be used in studies

of cell signaling pathways and mechanisms?

6.Explain and comment on this statement: The main function of

hor-mone receptors is that of signal amplification

7.Synaptic vesicles are approximately 40 nm in outside diameter, and

each vesicle contains about 10,000 acetylcholine molecules

Calcu-late the concentration of acetylcholine in a synaptic vesicle

8.GTPS is a nonhydrolyzable analog of GTP Experiments with squid

giant axon synapses reveal that injection of GTS into the

psynaptic end (terminal) of the neuron inhibits neurotransmitter re-lease (slowly and irreversibly) The calcium signals produced by presynaptic action potentials and the number of synaptic vesicles docking on the presynaptic membrane are unchanged by GTPS.

Propose a model for neurotransmitter release that accounts for all

of these observations

9. A typical hormone binds to its receptor with an affinity (KD) of ap-proximately 1 109M Consider an in vitro (test-tube) system in

which the total hormone concentration is approximately 1 nM and the total concentration of receptor sites is 0.1 nM What fraction of

the receptor sites is bound with hormone? If the concentration of

receptors is decreased to 0.033 nM, what fraction of receptor is

bound with the hormone?

10. (Integrates with Chapter 24.) All steroid hormones are synthesized

in the human body from cholesterol What is the consequence for steroid hormones and their action from taking a “statin” drug, such

as Zocor, which blocks the synthesis of cholesterol in the body? Are steroid hormone functions compromised by statin action?

11. Given that -strands provide a more genetically economical way

for a polypeptide to cross a membrane, why has nature chosen

-helices as the membrane-spanning motif for G-protein–coupled

receptors? That is, what other reasons can you imagine to justify the use of -helices?

12. Write simple reaction mechanisms for the formation of cAMP from ATP by adenylyl cyclase and for the breakdown of cAMP to 5-AMP

by phosphodiesterases

13. (Integrates with Chapter 9.) Consider the data in Figure 32.49a Recast Equation 9.2 to derive a form from which you could cal-culate the equilibrium electrochemical potential at which no net

systems bind with very high affinities to their receptors, displaying KD

val-ues in the range of 1012to 106M Hormones are produced at

concen-trations equivalent to or slightly above these KDvalues Once hormonal

effects have been induced, the hormone is usually rapidly metabolized

32.2 What Is Signal Transduction? Hormonal regulation depends

upon the transduction of the hormonal signal across the plasma

mem-brane to specific intracellular sites, particularly the nucleus Signal

trans-duction pathways consist of a stepwise progression of signaling stages:

receptor⎯→transducer⎯→effector The receptor perceives the signal,

trans-ducers relay the signal, and the effectors convert the signal into an

intra-cellular response Often, effector action involves a series of steps, each of

which is mediated by an enzyme, and each of these enzymes can be

con-sidered as an amplifier in a pathway connecting the hormonal signal to

its intracellular targets

32.3 How Do Signal-Transducing Receptors Respond to the Hormonal

Message? Steroid hormones may either bind to plasma membrane

receptors or exert their effects within target cells, entering the cell and

migrating to their sites of action via specific cytoplasmic receptor

pro-teins The nonsteroid hormones, which act by binding to

outward-facing plasma membrane receptors, activate signal transduction

path-ways that mobilize various second messengers—cyclic nucleotides, Ca2

ions, and other substances—that activate or inhibit enzymes or

cas-cades of enzymes in very specific ways

32.4 How Are Receptor Signals Transduced? Receptor signals are

transduced in one of three ways, to initiate actions inside the cell:

1 Exchange of GDP for GTP on GTP-binding proteins (G proteins),

which in turn leads to generation of second messengers, including

cAMP, phospholipid breakdown products, and Ca2

2 Receptor-mediated activation of phosphorylation cascades that in

turn trigger activation of various enzymes

3 Conformation changes that open ion channels or recruit proteins

into nuclear transcription complexes

32.5 How Do Effectors Convert the Signals to Actions in the Cell?

Transduction of the hormonal signal leads to activation of effectors— usually protein kinases and protein phosphatases—that elicit a variety

of actions that regulate discrete cellular functions Of the thousands

of mammalian kinases and phosphatases, the structures and functions

of a few are representative, including protein kinase A (PKA), protein kinase C (PKC), and protein tyrosine phosphatase SHP-2

32.6 How Are Signaling Pathways Organized and Integrated? All sig-naling pathways are organized in time and space in the cell, they are care-fully regulated, and they are integrated with one another PIDs modulate and control the association of signaling molecules with one another, of-ten in large signalsomes; signaling molecules are switched on and off by covalent modifications such as phosphorylations; and signaling often in-volves amplification and cooperative effects GPCR signaling can occur through G-protein-independent pathways and is sometimes modulated by RGS/GAPs Responses of signaling receptors can be coordinated by trans-activation, and signals from multiple pathways can be integrated

32.7 How Do Neurotransmission Pathways Control the Function of Sensory Systems? Nerve impulses, which can be propagated at speeds

up to 100 m/sec, provide a means of intercellular signaling that is fast enough to encompass sensory recognition, movement, and other phys-iological functions and behaviors in higher animals The generation and transmission of nerve impulses in vertebrates is mediated by an in-credibly complicated neural network that connects every part of the or-ganism with the brain—itself an interconnected array of as many as 1012

cells Despite their complexity and diversity, the nervous systems of ani-mals all possess common features and common mechanisms Physical or chemical stimuli are recognized by specialized receptor proteins in the membranes of excitable cells Conformational changes in the receptor protein result in a change in enzyme activity or a change in the perme-ability of the membrane These changes are then propagated through-out the cell or from cell to cell in specific and reversible ways to carry in-formation through the organism

1058 Chapter 32 The Reception and Transmission of Extracellular Information

flow of potassium would occur This is the Nernst equation

Cal-culate the equilibrium potential for Kand also for Na,

assum-ing T 37°C

14. The calculation of the actual transmembrane potential difference

for a neuron is accomplished with the Goldman equation:

where [C] and [A] are the cation and anion concentrations,

re-spectively, and PCand PAare the respective permeability coefficients

of cations and anions

Assume relative permeabilities for K, Na, and Clof 1, 0.04,

and 0.45, respectively, and use this equation to calculate the actual

transmembrane potential difference for the neuron whose ionic

concentrations are those given in Figure 32.49a

15. Use the information in problems 13 and 14, together with

Fig-ure 32.50, to discuss the behavior of potassium, sodium, and

chloride ions as an action potential propagates along an axon

16. Review the cell signaling pathway shown in Figure 32.4 With the

rest of the chapter as context, discuss all the steps of this pathway

that involve signal amplification

17. In the cell signaling pathway shown in Figure 32.4, what would be

the effect if Ras were mutated so that it had no GTPase activity?

18. One of the topics discussed in this chapter is the ability of GPCRs to

exert signaling effects without the involvement of G proteins Using

PC[C]outside PA[A]inside

PC[C]inside PA[A]outside

the pathway shown in Figure 32.40, and considering everything you have learned in this chapter, suggest some reasons that would ex-plain why this G-protein–independent signaling was difficult to ver-ify experimentally

Preparing for the MCAT Exam

19.Malathion (Figure 32.58) is one of the secrets behind the near-complete eradication of the boll weevil from cotton fields in the United States For most of the 20th century, boll weevils wreaked havoc on the economy of states from Texas to the Carolinas When boll weevils attacked cotton fields in a farming community, the de-struction of cotton plants meant loss of jobs for farm workers, bankruptcies for farm owners, and resulting hardship for the en-tire community Relentless application of malathion to cotton crops and fields has turned the tide, however, and agriculture ex-perts expect that boll weevils will be completely gone from cotton fields within a few years Remarkably, malathion-resistant boll wee-vils have not emerged despite years of this pesticide’s use Consider the structure and chemistry of malathion and suggest what you would expect to be the ecological consequences of chronic malathion application to cotton fields

20.Consult the excellent review article “Assembly of Cell Regulatory

Sys-tems Through Protein Interaction Domains” (Science 300:445–452,

2003, by Pawson and Nash) and discuss the structural requirements for a regulatory protein operating in a signaling network

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20 DNA 3  109bp, which, expressed in proteins 400 amino acids in length, could encode 2.5 106proteins

6 The amino acid side chains of proteins provide a range of shapes, polarity, and chemical features that allow a protein to be tailored to fit almost any possible molecular surface in a comple-mentary way

7 Biopolymers may be informational molecules because they are constructed of different monomeric units (“letters”) joined head to tail in a particular order (“words, sentences”) Polysac-charides are often linear polymers composed of only one (or two repeating) monosaccharide unit(s) and thus display little information content Polysaccharides with a variety of monosac-charide units may convey information through specific recogni-tion by other biomolecules Also, most monosaccharide units are typically capable of forming branched polysaccharide struc-tures that are potentially very rich in information content (as in cell surface molecules that act as the unique labels displayed by different cell types in multicellular organisms)

8 Molecular recognition is based on structural complementarity If complementary interactions involved covalent bonds (strong forces), stable structures would be formed that would be less re-sponsive to the continually changing dynamic interactions that characterize living processes

9 Two carbon atoms interacting through van der Waals forces are 0.34 nm apart; two carbon atoms joined in a covalent bond are 0.154 nm apart

10 Slight changes in temperature, pH, ionic concentrations, and so forth may be sufficient to disrupt weak forces (H bonds, ionic bonds, van der Waals interactions, hydrophobic interactions)

11 Living systems are maintained by a continuous flow of matter and energy through them Despite the ongoing transformations

of matter and energy by these highly organized, dynamic systems, no overt changes seem to occur in them: They are in a

steady state.

12 The fraction of the M genitalium genes encoding proteins 

0.925 Genes not encoding proteins encode RNA molecules (0.925)(580,074 base pairs)  536,820 base pairs devoted to protein-coding genes Since 3 base pairs specify an amino acid in a protein, 369 amino acids are found in the average

M genitalium protein If each amino acid contributes on average

120 D to the mass of a protein, the mass of an average

M genitalium protein is 44,280 D.

13 (0.925)(206)  191 proteins Assuming its genes are the same

size as M genitalium, the minimal genome would be 228,480

base pairs

For detailed answers to the end-of-chapter problems as well as

addi-tional problems to solve, see The Student Solutions Manual, Study

Guide and Problems Book by David Jemiolo and Steven Theg that

accompanies this textbook.

Chapter 1

1 Because bacteria (compared with humans) have simple

nutri-tional requirements, their cells obviously contain enzyme

systems that allow them to convert rudimentary precursors

(even inorganic substances such as NH4 , NO3 , N2, and CO2)

into complex biomolecules—proteins, nucleic acids,

polysaccha-rides, and complex lipids On the other hand, animals have an

assortment of different cell types designed for specific

physiolog-ical functions; these cells possess a correspondingly greater

repertoire of complex biomolecules to accomplish their

intri-cate physiology

2 Consult Figures 1.20 to 1.22 to confirm your answer

3 a Laid end to end, 250 E coli cells would span the head of a

pin

b The volume of an E coli cell is about 1015L

c The surface area of an E coli cell is about 6.3 1012m2 Its

surface-to-volume ratio is 6.3 106m1

d 600,000 molecules

e 1.7 nM.

f Because we can calculate the volume of one ribosome to be

4.2 1024m3(or 4.2 1021L), 15,000 ribosomes would

occupy 6.3 1017L, or 6.3% of the total cell volume

g Because the E coli chromosome contains 4600 kilobase pairs

(4.6 106bp) of DNA, its total length would be 1.6 mm—

approximately 800 times the length of an E coli cell This

DNA would encode 4300 different proteins, each 360 amino

acids long

4 a The volume of a single mitochondrion is about 4.2 1016L

(about 40% the volume calculated for an E coli cell in

problem 3)

b A mitochondrion would contain on average fewer than eight

molecules of oxaloacetate

5 a Laid end to end, 25 liver cells would span the head of a pin

b The volume of a liver cell is about 8 1012L (8000 times

the volume of an E coli cell).

c The surface area of a liver cell is 2.4 109m2; its

surface-to-volume ratio is 3 105m1, or about 0.05 (1/20) that of an

E coli cell Cells with lower surface-to-volume ratios are

limited in their exchange of materials with the environment

d The number of base pairs in the DNA of a liver cell is 6

109bp, which would amount to a total DNA length of 2 m

(or 6 feet of DNA!) contained within a cell that is only

Abbreviated Answers to Problems

A-2 Abbreviated Answers to Problems

14 Given 1109 nucleotides (or base pairs) per gene, the minimal

virus, with a 3500-nucleotide genome, would have only 3 genes;

the maximal virus, with a 280,000-bp genome, would have 252

genes

15 Fate of proteins synthesized by the rough ER:

a Membrane proteins would enter the ER membrane, and, as

part of the membrane, be passed to the Golgi, from which

vesicles depart and fuse with the plasma membrane

b A secreted protein would enter the ER lumen and be

trans-ferred as a luminal protein to the Golgi, from which vesicles

depart When the vesicle fuses with the plasma membrane,

the protein would be deposited outside the cell

16 Increasing kinetic energy increases the motions of molecules

and raises their average energy, which means that the difference

between the energy to disrupt a weak force between two

mole-cules and the energy of the weak force is smaller Thus,

in-creases in kinetic energy may break the weak forces between

molecules

17 Informational polymers must have “sense” or direction, and they

must be composed of more than one kind of monomer unit

Chapter 2

1 a 3.3; b 9.85; c 5.7; d 12.5; e 4.4; f 6.97

2 a 1.26 mM; b 0.25 mM; c 4 1012M; d 2 104M; e 3.16

1010M; f 1.26 107M (0.126

3 a [H] 2.51  105M; b Ka 3.13  108M; pKa 7.5.

4 a pH 2.38; b pH  4.23

5 Combine 187 mL of 0.1 M acetic acid with 813 mL of 0.1 M

sodium acetate

6 [HPO4 2]/[H2PO4 ] 0.398

7 Combine 555.7 mL of 0.1 M Na3PO4with 444.3 mL of 0.1 M

H3PO4 Final concentrations of ions will be [H2PO4 ] 0.0333

M; [HPO4 ] 0.0667 M; [Na] 0.1667 M; [H] 3.16 

108M.

8 Add 432 mL of 0.1 N HCl to 1 L 0.05 M BICINE [BICINE]total

0.05 M/1.432 L  0.0349 M [protonated form]  0.0302 M.

9 a Fraction of H3PO4: @pH 0 0.993; @pH 2  0.58; @pH 4 

0.01; negligible @pH 6

b Fraction of H2PO4 : @pH 0 0.007; @pH 2  0.41; @pH

4 0.986; @pH 6  0.94; @pH 8  0.14; negligible @pH 10

c Fraction of HPO4 : negligible @pH 0, 2, and 4; @pH 6

0.06; @pH 8 0.86; @pH 10 ⬇ 1.0; @pH 12  0.72

d Fraction of PO4 : negligible at any pH10; @pH 12  0.28

10 At pH 5.2, [H3A] 4.33  105M; [H2A] 0.0051 M;

[HA2] 0.014 M; [A3] 0.0009 M.

11 a pH 7.02; [H2PO4 ] 0.0200 M; [HPO4 ] 0.0133 M.

b pH 7.38; [H2PO4 ] 0.0133 M; [HPO4 ] 0.0200 M.

12 [H2CO3] 2(d)] 0.75 mM When [HCO3 ]

15 mM and [CO2(d)] 3 mM, pH  6.8.

13 Titration of the fully protonated form of anserine will require

the addition of three equivalents of OH The pKavalues lie at

2.64 (COOH); 7.04 (imidazole-NH); and 9.49 (NH3 ) Its

iso-electric point lies midway between pK2and pK3, so pHI 8.265

To prepare 1 L of 0.04 M anserine buffer, add 164 mL of 0.1 M

HCl to 400 mL of 0.1 M anserine at its isoelectric point, and

make up to 1 L final volume

14 Add 410 mL of 0.1 M NaOH to 250 mL of 0.1 M HEPES in its

fully protonated form and make up to 1 L final volume

15 166.7 g/mole

16 Add 193 mL of water and 307 mL of 0.1 M HCl to 500 mL of 0.1 M triethanolamine.

17 Combine 200 mL of 0.1 M Tris-Hwith 732 mL water and

68 mL of 0.1 M NaOH.

18 a

b

c The relevant pKafor this calculation is 8.3 Combine 400 mL

of 0.1 M bicine at its pHI(pH 5.3) with 155 mL of 0.1 M

NaOH and 345 mL of water

d The relevant pKafor this calculation is 2.3 The concentra-tion of fully protonated form of bicine at pH 7.5 is 2.18 

107M.

19 0.063 M

20 5.2 mM

21

22 0.0153 nmol/mL  sec

23 A drop in blood pH would occur

24 c

Chapter 3

1 Keq 613 M; G°  15.9 kJ/mol.

2.G°  1.69 kJ/mol at 20°C; G°  5.80 kJ/mol at 30°C.

S°  0.75 kJ/mol  K.

3.G 24.8 kJ/mol.

4 State functions are quantities that depend on the state of the system and not on the path or process taken to reach that state Volume, pressure, and temperature are state functions Heat and all forms of work, such as mechanical work and electrical work, are not state functions

5 G° G°  39.5 n (in kJ/mol), where n is the number of

Hproduced in any process So G° G°  39.5 n

30.5 kJ/mol  39.5(1) kJ/mol

G°  9.0 kJ/mol at 1 M [H]

0 2

0.2 0.4 0.6 0.8 1.0

4 6 8

equivalents OH–

pKa= 4.7

NCH2COO –

CH2CH2OH

CH2CH2OH

0 2

4 6 8 10 12

equivalents OH–

pKa= 2.3

pKa = 8.3