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9 Vitamins, Antioxidants, and Minerals

9 Vitamins, Antioxidants, and Minerals

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648



CHAPTER 19



Enzymes and Vitamins



Water-Soluble Vitamins

Vitamins are grouped by solubility into two classes: water-soluble and fat-soluble.

The water-soluble vitamins, listed in Table 19.5, are found in the aqueous environment inside cells, where most of them are needed as components of coenzymes.

Over time, an assortment of names, letters, and numbers for designating vitamins

have accumulated. Structurally, the water-soluble vitamins have ¬ OH, ¬ COOH,

or other polar groups that make them water soluble, but otherwise they range from

simple molecules like vitamin C to large, complex structures like vitamin B12.

Most vitamins are components of coenzymes, but some function as coenzymes

themselves. Vitamin C is biologically active without any change in structure from the

molecules present in foods. Similarly, biotin is connected to enzymes by an amide bond

at its carboxyl group but otherwise undergoes no structural change from dietary biotin.



A myriad of vitamin pills in capsule and

tablet form.





O

CH2OH

O



HOHC



O



HN



NH



HC



CH



H2C



CH



OH



OH



(CH2)4



COO–



S



Vitamin C

(Ascorbic acid)



Biotin



Other water-soluble vitamins are incorporated into coenzymes. The vitaminderived portions of two of the most important coenzymes, NAD+ and coenzyme A, are

illustrated in Figure 19.10. Table 19.5 includes the functions, deficiency symptoms, and

major dietary sources of water-soluble vitamins.

OH



OH



NH2



H

N+

+N



O



CH2



O



OH



C



P



O



O–

C



O

Nicotinamide



Niacin

(Nicotinic acid)



N



O



O



P



O



CH2



O



N



N



N



O–



NH2

OH



O



OH



Nicotinamide adenine dinucleotide (NAD+), a coenzyme



NH2



H2C



H2C



OH



O



P



H3C



C



CH3



H3C



C



CH3



HO



C



H



HO



C



H



C



O



C



O



O–



O



P



O



CH2



H2C



O



O

–O



H2C



C



OH



P

O–



H2C



O



H2C



C



O



NH



Pantothenic acid



Figure 19.10



The vitamin-derived portions of NAD + and coenzyme A.



N



O–



NH



NH







N



O



O



CH2



CH2



Coenzyme A



SH



OH

O



N

N



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SECTION 19.9



Vitamins, Antioxidants, and Minerals



649



table 19.5 The Water-Soluble Vitamins*

Reference Daily

Intake (RID)**

Effects of Deficiency



Effects of Excess



Milk, meat,

bread, legumes



1.2 mg



Muscle weakness, and

cardiovascular problems

including heart disease,

causes beriberi



Low blood pressure



In coenzymes flavin

mononucleotide (FMN)

and FAD



Milk, meat



1.3 mg



Skin and mucous membrane

deterioration



Itching, tingling

sensations



Niacin (nicotinic acid,

nicotinamide,B3)



In coenzyme NAD+



Meat, bread,

potatoes



16 mg



Nervous system, gastrointestinal, Itching, burning

sensations, blood

skin, and mucous membrane

vessel dilation, death

deterioration, causes pellagra

after large dose



B6 (pyridoxine)



In coenzyme for amino

acid and lipid metabolism



Meat, legumes



1.3 mg



Retarded growth, anemia,

convulsions, epithelial changes



Central nervous system

alterations, perhaps fatal



Folic acid



In coenzyme for amino

acid and nucleic acid

metabolism



Vegetables,

cereal, bread



0.4 mg



Retarded growth, anemia,

gastrointestinal disorders, neural

tube defects



Few noted except at

massive doses



B12 (cobalamin)



In coenzyme for nucleic

acid metabolism



Milk, meat



2.4 mg



Pernicious anemia



Excess red blood cells



Biotin



Coenzyme for

carboxylation reactions



Eggs, meat,

vegetables



0.3 mg



Fatigue, muscular pain, nausea,

dermatitis



None reported



In coenzyme A



Milk, meat



5 mg



Retarded growth, central nervous

system disturbances



None reported



Coenzyme; delivers

hydride ions; antioxidant



Citrus fruits,

broccoli, greens



90 mg



Epithelial and mucosal

deterioration, causing scurvy



Kidney stones



Thiamine 1B1 2

Vitamin



Riboflavin 1B2 2



Pantothenic acid 1B5 2



C (ascorbic acid)



Significance



Sources



In coenzyme for

decarboxylation

reactions



*Adapted in part from Frederic H. Martini, Fundamentals of Anatomy and Physiology, 4th edition (Prentice Hall, 1998).

**RDI values are the basis for information on the Nutrition Facts Label included on most packaged foods. The values are based on the Recommended

Dietary Intake Reports (2006–2011). See www.nap.edu.



Worked Example 19.6 Identifying Coenzymes

Identify the substrate, product, and coenzyme in the reaction shown. The reaction is catalyzed by the enzyme

alcohol dehydrogenase.

Ethanol + NAD+ ¡ Acetaldehyde + NADH + H +

AnAlySiS Identify which molecules have been changed and how, starting from the left side of the arrow (the



beginning of the reaction) to the right side of the arrow (the end of the reaction). In this case, ethanol is oxidized to acetaldehyde and NAD+ is reduced to NADH/H + . Recognize that nicotinamide adenine dinucleotide

1NAD+ 2 is a coenzyme involved in oxidation/reduction reactions.



Solution

Since NAD+ is a coenzyme involved in oxidation/reduction reactions, ethanol (the other molecule on the left

side of the equation) is the substrate and acetaldehyde (on the right side of the arrow) is the product of the

reaction. NADH + H + is the reduced form of NAD+ and is considered to be reduced coenzyme only—not a

product of the reaction.

ProBlEM 19.17 Does the enzyme described in each of the following statements

require a cofactor to be active?

(a) Ni2+ is present in the active site.

(b) Addition of FAD allows the reaction to occur.

(c) The presence of K+ does not affect the reaction.



ProBlEM 19.18 Which vitamin provides us with each of the following?

(b) Coenzyme A

(a) NAD +



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650



CHAPTER 19



Enzymes and Vitamins



Fat-Soluble Vitamins

Fat-soluble vitamins A, D, E, and K are stored in the body’s fat deposits. Although the

clinical effects of deficiencies of these vitamins are well documented, the molecular

mechanisms by which they act are not nearly as well understood as those of the watersoluble vitamins. None have been identified as a coenzyme. Table 19.6 summarizes the

functions, sources, and deficiency symptoms of fat-soluble vitamins. The hazards of

overdosing on fat-soluble vitamins are greater than the hazards of overdosing on watersoluble vitamins because the fat-soluble vitamins accumulate in body fats. Excesses of

the water-soluble vitamins are more likely to be excreted in the urine.



ProBlEM 19.19

Compare the structures of vitamin A and vitamin C. Which one is water-soluble and

which is fat-soluble? What structural features does each have that make one watersoluble and the other fat-soluble?

H3C



CH3



Deeply pigmented vegetables and

fruits contain vitamins.



CH3



CH3



CH2OH

CH2OH



O



HOCH



O







CH3



OH

Vitamin A

(Retinol)



OH



Vitamin C

(Ascorbic acid)



table 19.6 The Fat-Soluble Vitamins*

Vitamin



Significance



Sources



A



Essential for night vision, healthy

eyes, and normal development of

epithelial tissue; antioxidant



Leafy green and

yellow vegetables



D



Required for normal bone

growth, calcium and phosphorus

absorption at gut, and retention in

kidneys



E

K



Reference

Daily Intake**



Effects of Deficiency



Effects of Excess



900 mg



Retarded growth, night

blindness, deterioration of

epithelial membranes



Liver damage, skin peeling,

central nervous system effects

(nausea, anorexia)



Synthesized in

skin exposed to

sunlight



15 mg



Rickets, skeletal

deterioration



Calcium deposits in many

tissues, disrupting functions



Prevents breakdown of vitamin A

and fatty acids; antioxidant



Meat, milk,

vegetables



15 mg



Anemia, other problems

suspected



None reported



Essential for liver synthesis of

prothrombin and other clotting

factors



Vegetables;

production by

intestinal bacteria



120 mg



Bleeding disorders



Liver dysfunction, jaundice



*Adapted in part from Frederic H. Martini, Fundamentals of Anatomy and Physiology, 4th edition (Prentice Hall, 1998).

**RDI values are the basis for information on the Nutrition Facts Label included on most packaged foods. The values are based on the Recommended Dietary Intake Reports

(2006–2011). See www.nap.edu. RDIs for fat-soluble vitamins are often reported in International Units (IU), which are defined differently for each vitamin. The values given

here are approximate equivalents in mass units.



ProBlEM 19.20

Based on the structure shown for retinol (vitamin A) and the names of the two related

forms of vitamin A, retinal and retinoic acid, what do you expect to be the structural

differences among these three compounds?



Antioxidants

Antioxidant A substance that prevents

oxidation by reacting with an oxidizing

agent.



Free radical An atom or molecule

with an unpaired electron.



An antioxidant is a substance that prevents oxidation. The food industry uses antioxidants to combat oxidation of unsaturated fats by air, which causes deterioration of

baked goods. In the body, we need similar protection against active oxidizing agents

that are byproducts of normal metabolism.

Our principal dietary antioxidants are vitamin C, vitamin E, b@carotene, and the

mineral selenium. They work together to defuse the potentially harmful action of free

radicals, highly reactive molecular fragments with unpaired electrons (e.g., superoxide

ion, # O2- ). Free radicals quickly gain stability by picking up electrons from nearby molecules, which are left damaged.



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SECTION 19.9



Vitamins, Antioxidants, and Minerals



Vitamin E is unique in having antioxidant activity as its principal biochemical role.

It acts by giving up the hydrogen from its ¬ OH group to oxygen-containing free radicals. The hydrogen is then restored by reaction with vitamin C. Selenium joins the list

of important antioxidants because it is a cofactor in an enzyme that converts hydrogen

peroxide 1H2O2 2 to water before the peroxide can go on to produce free radicals.



651



looKing AHEAD

The role of vitamins as antioxidants is explored further

in the discussion of elimination of cellular damaging reactive oxygen species

in the Chemistry in Action “Harmful

Oxygen Species and Antioxidant Vitamins,” page 703.



KEy ConCEPt ProBlEM 19.21



Vitamins are a diverse group of compounds that must be present in the diet. List four

functions of vitamins in the body.



ProBlEM 19.22

See the Chemistry in Action “Vitamins, Minerals, and Food Labels” below. Which vitamin listed on the label functions as an antioxidant in the body? Why is this important?



CHEMiStry in ACtion

Vitamins, Minerals, and Food Labels

It is not uncommon to encounter incomplete or incorrect information about vitamins and minerals. We have been frightened

by the possibility that aluminum causes Alzheimer’s disease

and tantalized by the possibility that vitamin C defeats the

common cold. Sorting out fact from fiction or distinguishing

preliminary research results from scientifically proven relationships is especially difficult in this area of nutrition.

One consistent source of information on nutrition is the

Food and Nutrition Board of the National Academy of SciencesNational Research Council. They periodically survey the latest

nutritional information and publish Recommended Dietary Allowances (RDAs) that are “designed for the maintenance of

good nutrition of the majority of healthy persons in the United

States.” Another source is the U.S. Food and Drug Administration (FDA), which sets the guidelines for food labeling.

Since 1994, as mandated by the FDA, most packaged food

products carry standardized Nutrition Facts labels. The nutritional value of a food serving

Nutrition Facts

of a specified size is reported

Serving Size 55 pieces (30g)

Servings Per Container About 6

as % Daily Value. For vitamins

and minerals, these percentAmount Per Serving

Joules from Fat 188

Joules 585

ages are calculated from RDI

% Daily Value*

values published in 1968. RDIs

8%

Total Fat 5g

5%

Saturated Fat 1g

are averages for adults and

Trans Fat 0g

children over 4 years of age.

Polyunsaturated Fat 1.5g

The values for vitamins are inMonounsaturated Fat 2.5g

Cholesterol Less than 5mg 1%

cluded in Tables 19.5 and 19.6.

Sodium 250mg

10%

For minerals, they are listed in

Total Carbohydrate 19g 6%

the accompanying table.

Dietary Fiber 2g

7%

Sugars Less than 1g

All vitamins and minerals

Protein 4g

are important and essential,

but in choosing which vitaVitamin C 0%

Vitamin A 0%

Iron

6%

Calcium 4%

mins and minerals must be

Percent Daily Values are based on a 8350

joules diet. Your daily values may be higher

listed on the new labels, the

or lower depending on your caloric needs:

Energy (J): 8350

10,500

government has focused on

Total Fat

Less than

65g

80g

Sat. Fat

Less than

20g

25g

those currently of greatest imCholesterol Less than

300mg

300mg

Sodium

Less than

2,400mg 2,400mg

portance in maintaining good

Total Carbohydrate

300g

375g

Dietary Fiber

25g

30g

health. The choices reflect a

*



new emphasis on preventing disease rather than preventing

deficiencies. The mandatory listings are for vitamin A, vitamin C,

calcium, and iron. These recommendations are based on evidence for the benefits of high dietary levels of the antioxidants

vitamin A (or the related compound, b@carotene) and vitamin C.

Calcium deficiencies are related to osteoporosis, and iron deficiencies are a special concern for women because of their menstrual blood loss.

Reference Daily Intake Values* for Minerals

Mineral



RDI



Mineral



RDI



Calcium



1.0 g



Selenium



70 mg



Iron



18 mg



Manganese



2 mg



Phosphorus



1.0 g



Fluoride



2.5 mg



Iodine



150 mg



Chromium



120 mg



Magnesium



400 mg



Molybdenum



75 mg



Zinc



15 mg



Chloride



3.4 g



Copper



2 mg



*On Nutrition Facts labels, calcium and iron must be listed; phosphorus, iodine,

magnesium, zinc, and copper listings are optional; by law, the others cannot be

listed.



CiA Problem 19.4 Which vitamins and minerals are listed on

the food label and in what amount? Is this a good nutritional

choice for consuming these vitamins and minerals?

CiA Problem 19.5 Read the labels on foods that you eat for a

day, or look up the foods in a nutrition table and determine

what percent of your daily dosage of vitamins and minerals you get from each. Are you getting the recommended

amounts from the food you eat, or should you be taking a

vitamin or mineral supplement?

CiA Problem 19.6 For what reasons are listings for vitamin A,

vitamin C, iron, and calcium mandatory on food labels?

CiA Problem 19.7 In addition to the four nutrients named in

CIA Problem 19.6, what other nutrients may be listed on

food labels? (Hint: Look at all the ingredients that have

amounts listed on the label shown.)



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CHAPTER 19



Enzymes and Vitamins



Minerals

The other important group of micronutrients is minerals, some of which are transition group

elements. Table 19.7 lists the essential minerals, their sources and functions. A balanced diet

supplies sufficient amounts of each of these micronutrients. Many of the transition elements

are necessary for proper functioning of enzymes, since these elements are used as cofactors.

Other minerals are used as building blocks for the body and some exist as ions, called electrolytes, in our body fluids. The RDI for most of these minerals is listed in the Chemistry in

Action “Vitamins, Minerals, and Food Labels.”

Dietary minerals are divided into macrominerals, those with required daily amounts

greater than 100 mg per day, and microminerals, those needed in lesser quantities. The

macrominerals listed in Table 19.7 do not include sulfur because it is an integral part

of the amino acids cysteine and methionine, which are taken in sufficient amounts in

the diet. Adequate, regular intake of calcium and phosphorus is necessary for formation and maintenance of bone. Magnesium is also necessary for bone metabolism and

is stored in bone tissue; it is also a cofactor in many different enzymes ranging from

glucose and lipid metabolism to protein synthesis.

We generally do not think of the other three macrominerals as essential, since deficiencies are rare. Rather, we often consume too much sodium, chloride, and potassium

by eating processed food. These macronutrients function as electrolytes, maintaining



table 19.7 Macro and Trace Minerals

Mineral



Effects of

Deficiency



Significance



Sources



Effects of Excess



Calcium



Bone formation, muscle contraction



Dairy, eggs, beans



Osteoporosis,

muscle cramps



Kidney stones, heart arrhythmias



Phosphorus



Bone formation, component of DNA

and energy molecules



Any protein



Muscle weakness



Impaired calcium metabolism



Potassium



Osmotic balance inside cells



Fruit, vegetables, meat



Loss of appetite,

muscle cramps



Inhibited heart function



Chloride



Primary negative ion in extracellular

fluid



All foods, especially

processed



Convulsions (rare)



Hypertension



Sodium



Nerve impulse conduction,

electrolyte (osmotic balance)



All foods, especially

processed



Muscle cramps,

nausea



Hypertension



Magnesium



Protein synthesis, glucose

metabolism



Dairy, whole grains, plants



Muscle weakness



Nausea



Iron



Hemoglobin and cytochrome

component



Meat, whole grains, legumes



Fatigue, anemia



Hemochromatosis



Fluoride



Part of vitamin B12



Milk, eggs, seafood



Dental cavities



Discolored teeth



Zinc



Enzyme cofactor, smell and taste

functions



Meat, dairy, whole grains



Poor immune

function, slow

wound healing



Poor immune system, increased

low-density lipoprotein (LDL)

cholesterol



Copper



Enzymes for oxidations and

connective tissue formation



Meat, nuts, eggs, bran cereal



Anemia



Nausea



Selenium



Cofactor for glutathione peroxidase



Meat, whole grains



Cardiac muscle

damage



Nausea, hair loss



Manganese



Coenzyme for many enzymes in

energy metabolism



Whole grains, legumes



Poor growth



Weakness, mental confusion



Macrominerals



Microminerals



Iodine



Production of thyroid hormones



Iodized salt, seafood



Goiter



Depressed thyroid activity



Molybdenum



Coenzyme



Meat, whole grains, legumes



Not found



Not found



Chromium



Enhances insulin function



Meat, whole grains



Glucose

intolerance



Rare from diet



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Vitamins, Antioxidants, and Minerals



SECTION 19.9



653



CHEMiStry in ACtion

Enzymes in Medical Diagnosis



Enzyme



Diagnosis



Aspartate transaminase (AST)



Damage to heart or liver



Alanine transaminase (ALT)



Damage to heart or liver



Lactate dehydrogenase (LDH)



Damage to heart, liver, or red blood

cells



Alkaline phosphatase (ALP)



Damage to bone and liver cells



g@Glutamyl transferase (GGT)



Damage to liver cells; alcoholism



Creatine phosphokinase (CPK-2)



Damage to heart



Acid phosphatase



Prostate cancer



Enzyme analysis measures the activity of an enzyme

rather than its concentration. Because activity is influenced

by pH, temperature, and substrate concentration, it is measured in IU at standard conditions. One IU is defined as the

amount of an enzyme that converts 1 mmol of its substrate to

product per minute under defined standard conditions of pH,

temperature, and substrate concentration. The analytical results are reported in units per liter (U/L).

Enzyme assays are done to diagnose heart attacks (myocardial infarctions, MI), like in Mr. Smith’s case at the beginning

of the chapter, and differentiate them from other conditions

like liver disease. CPK has three isomeric forms: CPK-1 is found

in brain tissue, CPK-2 is found in heart tissue, and CPK-3 is

found in skeletal muscle. After an MI, CPK-2 values rise rapidly within 6 hours and peak around 12 hours after the event,

then decrease. AST and ALT blood levels are also measured to

help in diagnosis but are also indicators of liver disease. LDH,

which has five isomeric forms, one of which is found only in

heart muscle, formerly was used as an MI indicator. Currently



Troponin

Relative level above normal



In a healthy person, certain enzymes, such as those responsible for forming and dissolving blood clots, are normally

present in high concentrations in blood serum. Enzymes that

function within cells are found normally in low concentrations in blood serum due to normal degeneration of healthy

cells. However, when tissue is injured, large quantities of

cellular enzymes are released into the blood from dying

cells, with the distribution of enzymes and other proteins

dependent on the identity of the injured cells. Measurement

of blood levels of specific molecules is therefore a valuable

diagnostic tool. For example, higher-than-normal activities of

the enzymes included in a routine blood analysis indicate the

following conditions:



CPK



AST

LDH



0



1



2



3



4

Days



5



6



7



Blood levels of troponins, CPK-2, AST, and LDH in the days

following a heart attack.





the levels of troponin proteins are measured in blood samples

over 18 hours. There are several troponin isomers; cardiac troponin is specific to heart muscle cells and is associated with

actin and myosin in cells; troponins are not enzymes but are

a reliable marker for an MI. Troponin levels rise rapidly immediately and dramatically after an MI, decreasing over several

days post event rise.

What happened to Mr. Smith and Ms. Givens from the beginning of the chapter? Physicians determined from elevated CPK

and AST levels (both enzymes), the characteristic rise in troponin levels (determined in an assay involving enzymes), and

other tests that Mr. Smith had a heart attack. His blood lipids

were also elevated, and he was placed on a heart-healthy diet

along with appropriate medications. Ms. Givens, indeed, had

suffered an ischemic stroke, blocking blood circulation in part

of her brain. She was promptly treated with an intravenous infusion of tPA, an enzyme obtained from recombinant DNA technology. Early treatment with tPA results in clot dissolution and

better recovery from a stroke. Ms. Givens was also given diet

recommendations and medications before discharge from the

hospital.

CiA Problem 19.8 Enzyme levels in blood are often elevated

in various disease states. Which enzyme or other blood

marker gives the earliest indication of a heart attack?

Which test is used to confirm a heart attack, after several

tests over several days?

CiA Problem 19.9 Why must enzyme activity be monitored

under standard conditions?



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654



CHAPTER 19



Enzymes and Vitamins



osmotic balance in both intracellular and extracellular spaces. They also help in the

production of electrical signals throughout the nervous system; potassium ions are important in regulating heartbeat.

Magnesium and selenium, along with the transition elements chromium, copper,

manganese, molybdenum, and zinc, are classed as micronutrients. Our bodies need only

tiny amounts of these elements to supply enough cations to function as cofactors for

enzymes. Some of these elements, such as copper and selenium, are highly toxic if

ingested in high amounts. Each of these transition elements exists as a cation that can

form covalent-coordinated bonds with specific, charged residues in the protein structure of their respective enzymes. Because these are transition element cations, with

variable oxidation states, they can also serve as transient holders of electrons during

enzymatic reactions.

Vitamins and micronutrient minerals serve complementary functions. Both serve

as cofactors for enzymatic reactions. Minerals serve directly, whereas vitamins may be

modified into other organic molecules in order to participate in a reaction. The other

essential minerals are used as building material or to maintain electrolyte balance.



ProBlEM 19.23

Which micronutrient mineral do you think is the most toxic in excess? Why is it necessary if it is toxic?



SuMMAry



rEViSiting tHE CHAPtEr lEArning oBJECtiVES



• Describe the function of enzymes in biochemical reactions.

Enzymes are the catalysts for biochemical reactions, acting by lowering the activation energy needed for the reaction. They are mostly

water-soluble, globular proteins (see Problems 84 and 85).

• Explain the role of cofactors in some enzymatic reactions. Some

enzymes require cofactors, which are either metal ions or the nonprotein organic molecules known as coenzymes, for activity. These

cofactors facilitate electron transfer and chemical group movement

during the reaction (see Problems 25, 27, and 32–35).

• give an enzyme the appropriate name given the substrate.

Enzymes are named for the substrate (first part of the name) and

type of reaction involved (second part of the name) with the suffix

-ase attached. Some enzymes retain classical names and do not

follow these rules (see Problems 25, 36, and 37).

• Assign an enzyme to the correct class based on its reaction.

There are six major classes of reactions that are catalyzed by

enzymes. Each major class encompasses subclasses of similar

reactions (Table 19.2) (see Problems 25, 36, 37, and 41–46).

• Explain the two models of enzyme catalysis. In the lock-and-key

model of catalysis, the substrate fits the active site of the enzyme

like a key fits a lock. It is a rigid model. In the induced-fit model,

substrate is drawn into the active site by noncovalent interactions.

As the substrate enters the active site, the enzyme shape adjusts

to best accommodate the substrate and catalyze the reaction (see

Problems 40, 41, 48, and 49).

• Describe how an enzyme and substrate combine to facilitate a

reaction. Within the enzyme–substrate complex, the substrate is held

in the best orientation for reaction and in a strained condition that

allows the activation energy to be lowered. When the reaction is complete, the product is released and the enzyme returns to its original

condition. The specificity of each enzyme is determined by the presence within the active site of catalytically active groups, hydrophobic

pockets, and ionic or polar groups that exactly fit the chemical makeup

of the substrate (see Problems 24, 30, 50–53, 81, and 82).



• Describe the changes in enzyme activity that result when substrate concentration, enzyme concentration, temperature, or pH

change. With fixed enzyme concentration, reaction rate first increases

with increasing substrate concentration and then approaches a fixed

maximum at which all active sites are occupied. In the presence of

excess substrate, reaction rate is directly proportional to enzyme

concentration. With increasing temperature, reaction rate increases

to a maximum and then decreases as the enzyme protein denatures.

Reaction rate is maximal at a pH that reflects the pH of the enzyme’s

site of action in the body (see Problems 54–57 and 82).

• Define and identify reversible and irreversible inhibition. The

effectiveness of enzymes is controlled by a variety of activation and

inhibition strategies. Competitive inhibitors are reversible inhibitors that

typically resemble the substrate and reversibly block the active site;

they slow the reaction rate but do not change the maximum rate. Irreversible inhibitors form covalent bonds to an enzyme that permanently

inactivate it; most are poisons (see Problems 30, 62, 64, and 65).

• Define and identify uncompetitive and competitive inhibition.

Uncompetitive inhibitors act on the enzyme–substrate complex,

blocking a second substrate from entering the active site; they lower

the maximum reaction rate. Competitive inhibitors are molecules

similar to the substrate that fit the active site and slow the reaction

rate (see Problems 28 and 58–61).

• Define and identify allosteric control. Allosteric control is

achieved by an enzyme regulator molecule that can exercise control

over an enzyme by binding to a site different from the active site.

Binding a regulator induces a change of shape in the active site,

increasing or decreasing the efficiency of the enzyme. The regulator molecule does not need to resemble the reaction substrate (see

Problems 29, 30, 66, and 67).

• Define feedback control and explain how it regulates enzyme catalysis. Feedback control acts through allosteric control of enzymes

that have regulatory sites separate from their active sites. When

enough product of a series of reactions is present, the excess inhibits



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Key Words

the activity of the first enzyme in the reaction series preventing more

product from accumulating (see Problems 29, 30, 68, and 69).

• Define and identify inhibition by covalent modification. Enzyme activity is also regulated by reversible phosphorylation and dephosphorylation and by synthesis of inactive zymogens that are later activated by

removal of part of the molecule (see Problems 29, 71, and 73).

• Define and identify inhibition by genetic control of enzymes.

Genetic control is exercised by regulation of the synthesis of

enzymes specific to the stage of life and need of the organism

(see Problems 29, 30, 70, and 72).

• Describe the two classes of vitamins, the reasons vitamins are

necessary in the diet, and the results of vitamin excesses or deficiencies. Vitamins are organic molecules required in small amounts

in the body that must be obtained from the diet. The water-soluble

vitamins (Table 19.5) are coenzymes or parts of coenzymes. The



655



fat-soluble vitamins (Table 19.6) have diverse and less well-understood functions. In general, excesses of water-soluble vitamins are

excreted and excesses of fat-soluble vitamins are stored in body fat,

making excesses of the fat-soluble vitamins potentially more harmful (see Problems 80, 81, and 88).

• identify antioxidants and explain their function. Vitamin C,

b@carotene (a precursor of vitamin A), vitamin E, and selenium work

together as antioxidants to protect biomolecules from damage by

free radicals.

• identify essential minerals, explain why minerals are necessary

in the diet, and explain the results of mineral deficiencies. Minerals

are chemical elements needed in small amounts in the diet. Minerals

function as macronutrients (calcium and phosphorus for bone), electrolytes, and micronutrients used primarily as enzyme cofactors.



CONCEPT MAP: ENZYMES

Enzymes

are



have



may need



Proteins



Activity



Cofactors



with



affected by



moderated by



pH



Allosteric effectors



Temperature



Feedback control



Concentrations



Zymogen production



Inhibitors



Genetic control



Metal ions



3° and 4° structure



Coenzymes



that contain

Derived from vitamins

Active site

binds

Substrate

connects to

Product

Reversible



Not reversible



Covalent modification



Competitive



Uncompetitive



Figure 19.11 Concept Map. Protein tertiary and quaternary structures provide active sites where biochemical reactions occur

in enzymes. Activity is affected by several physical factors and can be affected by inhibitory molecules. Several different forms of

control, depending on the enzyme, control activity. Some enzymes require cofactors, either metal ions or coenzymes, for activity.







KEY WORDS

Activation (of an enzyme),

p. 639

Active site, p. 626

Allosteric control, p. 642

Allosteric enzyme, p. 642

Antioxidant, p. 650

Coenzyme, p. 627

Cofactor, p. 627



Competitive (enzyme)

inhibition, p. 640

Enzyme, p. 625

Feedback control, p. 644

Free radical, p. 650

Genetic (enzyme) control,

p. 647

Induced-fit model, p. 633



Inhibition (of an enzyme),

p. 639

Irreversible (enzyme)

inhibition, p. 641

Lock-and-key model,

p. 633

Specificity (enzyme),

p. 626



Substrate, p. 626

Turnover number, p. 627

Uncompetitive (enzyme)

inhibition, p. 640

Vitamin, p. 647

Zymogen, p. 645



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656



Enzymes and Vitamins



CHAPTER 19



unDErStAnDing KEy ConCEPtS

19.24

On the following diagram, indicate with dotted lines the

bonding between the enzyme (a dipeptidase; several amino acid

residues in black) and the substrate (in blue) that might occur to

form the enzyme–substrate complex. What are the two types of

bonding likely to occur?



H

O

C

O



+

H3N



(a) Covalent modification



N



H



N



H



O



H



H



C



C



N



C



O–



R



+

O– H3N

C

O



R′



19.25

Answer questions (a)–(e) concerning the following

reaction:

–O

HO



–O



O

C



O



NAD+ NADH/H+ C



C

H



CH3

L-Lactate



19.28

Explain how the following changes affect the rate of an

enzyme-catalyzed reaction in the presence of an uncompetitive

inhibitor: (a) increasing the substrate concentration at a constant

inhibitor concentration, (b) decreasing the inhibitor concentration

at a constant substrate concentration.

19.29

Explain how the following mechanisms regulate enzyme

activity.



O



C

CH3



Pyruvate



(a) The enzyme involved in this reaction belongs to what

class of enzymes?



(b) Genetic control



(c) Allosteric regulation

(d) Feedback inhibition

19.30

What type of enzyme regulation occurs in the following

situations?

(a) Buildup of the product of the pathway that converts

glucose to pyruvate stops at the first enzyme in the

multistep process.

(b) Sarin, a nerve gas, covalently binds to acetylcholinesterase, stopping nerve signal transmission.

(c) Lactase is not produced in the adult.

(d) Conversion of isocitrate to a@ketoglutarate is inhibited by high levels of ATP. (Hint: ATP is neither a

product nor a substrate in this reaction.)

19.31

Acidic and basic groups are often found in the active

sites of enzymes. Identify the acidic and basic amino acids in the

active site in the following diagram. (Hint: Consult Table 18.3 and

Chapter 10 for the definition of acids and bases.)

(CH2)2



(b) Since hydrogens are removed, the enzyme belongs to

what subclass of the enzyme class from part (a)?



C



(c) What is the substrate for the reaction as written?



CH2OH



O



NH2



(d) What is the product for the reaction as written?



(CH2)3



(e) The enzyme name is derived from the substrate name

and the subclass of the enzyme and ends in the familyname ending for an enzyme. Name the enzyme.

19.26

In the reaction shown in Problem 19.25, will the enzyme

likely also use d-lactate as a substrate? Explain your answer. If

d-lactate binds to the enzyme, how is it likely to affect the enzyme?

19.27

In the reaction shown in Problem 19.25, identify the

coenzyme required for catalytic activity. Is the coenzyme an oxidizing agent or a reducing agent? What vitamin is a part of the

coenzyme for this reaction?



NH



CH2COO–

+



C



H2N



H



NH2

CH2



N

N



ADDitionAl ProBlEMS

ENZYME COFACTORS (SECTION 19.2)



19.34 Which of these vitamins can serve as a cofactor?



19.32 Name the vitamin to which each of these coenzymes is

related.

(a) FAD



(b) Coenzyme A



(c) NAD+

19.33 Which of the following is a cofactor and which is a

coenzyme?

(a) Cu2+

(c) NAD



(b) Tetrahydrofolate

+



(d) Mg 2+



(a) Vitamin A



(b) Vitamin C



(c) Vitamin D

19.35 Which of the following is a cofactor and which is a

coenzyme?

(a) Fe2+



(b) Pyridoxyl phosphate



(c) FAD



(d) Ni2+



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Additional Problems



STRUCTURE AND CLASSIFICATION OF ENZYMES (SECTION 19.3)



(a) Dehydrogenases



H



(b) O

C



19.36 What general kinds of reactions do the following types of

enzymes catalyze?



CH2



HCOH



(b) Decarboxylases



P



O



19.38 Name an enzyme that acts on each molecule.



C

–O



19.44 What kind of reaction does each of these enzymes

catalyze?

(a) A ligase

(b) A transmethylase



O



(c) A reductase

19.45 What kind of reaction does each of these enzymes

catalyze?



R′

O



O



(a) A dehydrase

(b) A carboxylase



H2NCHCOH + H2NCHCOH



(c) A protease



R′



19.46 The following reaction is catalyzed by the enzyme urease.

To what class of enzymes does urease belong?



O

CH2



C



COOH



O



O

CH3



H2N



C



COOH



O



+ CO2



O



(c) HOCCH2CH2COH



O



C



C

+

+ H3NCH



CH3



Vitamin B6



CH2



Pyruvate



O–



L-Aspartate



NH2 + 2 H2O



Urease



2 NH3 + H2CO3



19.47 Alcohol dehydrogenase (ADH) catalyzes the following

reaction. To what class of enzymes does ADH belong?



O



O



HOCCH



CHCOH



C

+

H3NCH



NAD+ NADH/H+



CH3



+ O



CH3



O



C

CH2

C



O



CH2

Ethanol



C



L-Alanine



C

O



C

Urea



19.43 What classes of enzymes would you expect to catalyze the

following reactions?

(a)

–O

–O

–O

–O

O

O

O

C



O



Oxaloacetate



(a) H2NCHCNHCHCOH + H2O



(b) HOOC



O



CH2



(c) RNA



19.42 What classes of enzymes would you expect to catalyze the

following reactions?



R



C

C



Pyruvate



19.41 Describe in general terms how enzymes act as catalysts.



R



ADP



O + CO2



19.40 What features of enzymes make them so specific in their

action?



O



O–



O



CH3



19.39 Name an enzyme that acts on each molecule.



P



O–



Oxaloacetate



O–



Dihydroxyacetone phosphate



ATP



C

(c) DNA



(b) Protein



O



O–



C



(a) Lactose



O



CH2



O–



(c) O



(c) Synthetases

(b) Peroxide



C



O–



3-Phosphoglyceraldehyde



(b) Isomerases



(a) Amylose



OH



O–



19.37 What general kinds of reactions do the following types of

enzymes catalyze?

(a) Kinases



O



O



CH2



(c) Lipases



657



OH



CH3



O

C

H



Acetaldehyde



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Enzymes and Vitamins

enzyme glycopeptide transpeptidase and does not

dissociate.



HOW ENZYMES WORK (SECTION 19.4)

19.48 What is the difference between the lock-and-key model of

enzyme action and the induced-fit model?



(b) Accidental methanol consumption is fairly common.

The treatment includes the ingestion of ethanol. Both

molecules can be converted to aldehydes by alcohol

dehydrogenase. Ethanol is the true substrate.



19.49 Why is the induced-fit model a more likely model than the

lock-and-key model?

19.50 Must the amino acid residues in the active site be near each

other along the polypeptide chain? Explain.



19.52 How do you explain the observation that pepsin, a digestive enzyme found in the stomach, has a high catalytic

activity at pH 1.5, while trypsin, an enzyme of the small

intestine, has no activity at pH 1.5?

19.53 Amino acid side chains in the active sites of enzymes can

act as acids or bases during catalysis. List the amino acid

side chains that can accept H + and those that can donate

H + during enzyme-catalyzed reactions.



FACTORS AFFECTING ENZYME ACTIVITY (SECTION 19.5)

19.54 If the rate of an enzymatic reaction doubles when the

amount of enzyme is doubled, what do you expect the rate

of reaction to be if the amount of enzyme is tripled? Why?



19.60 EcoRI, an enzyme that hydrolyzes DNA strands, requires

Mg 2+ as a cofactor for activity. EDTA chelates divalent

metal ions in solution. In the graphs shown here, the arrow

indicates the point at which EDTA is added to a reaction

mediated by EcoRI. Which graph represents the activity

curve you would expect to see? (Activity is shown as total

product from the reaction as time increases.)

Enzyme activity



19.51 The active site of an enzyme is a small portion of the enzyme molecule. What is the function of the rest of the huge

molecule?



(c) The antibiotic deoxycycline inhibits the bacterial enzyme collagenase, slowing bacterial growth. Deoxycycline does not fit into the active site of collagenase and

binds elsewhere on the enzyme.



A



Enzyme activity



CHAPTER 19



Enzyme activity



658



B



C



19.55 What happens to the rate of an enzymatic reaction if the

amount of substrate is doubled? Why?

19.56 What general effects would you expect the following

changes to have on the rate of an enzyme-catalyzed reaction for an enzyme that has its maximum activity at body

temperature (about 37 °C/310.15 K)?

(a) Raising the temperature from 310 K (37 °C) to 343 K

(70 °C)

(b) Lowering the pH from 7 to 3

(c) Adding an organic solvent, such as methanol

19.57 What general effects would you expect the following

changes to have on the rate of an enzyme-catalyzed reaction for an enzyme that has its maximum activity at body

temperature (about 37 °C/310.15 K)?

(a) Lowering the reaction temperature from 313 K (40 °C)

to 283 K (10 °C)

(b) Adding a drop of a dilute HgCl2 solution

(c) Adding an oxidizing agent, such as hydrogen peroxide



ENZYME REGULATION: INHIBITION (SECTION 19.6)

19.58 The text discusses three forms of enzyme inhibition: uncompetitive inhibition, competitive inhibition, and irreversible inhibition.

(a) Describe how an enzyme inhibitor of each type works.

(b) What kinds of bonds are formed between an enzyme

and each of these three kinds of inhibitors?

19.59 What kind of inhibition (uncompetitive, competitive, or

irreversible) is present in each of the following:

(a) Penicillin is used to treat certain bacterial infections. Penicillin is effective because it binds to the



19.61 The enzyme lactate dehydrogenase converts lactic acid

to pyruvate with the aid of the coenzyme NAD+. In the

graphs of Problem 19.60, the arrow indicates the point

at which EDTA is added to a reaction mixture of lactic

dehydrogenase and lactic acid. Which graph represents the

activity curve you would expect to see? (Activity is shown

as total product from the reaction as time increases.)

19.62 Lead exerts its poisonous effect on enzymes by two

mechanisms. Which mechanism is irreversible and why?

19.63 One mechanism by which lead exerts its poisonous effect

on enzymes can be stopped by chelation therapy with

EDTA. Describe this type of lead poisoning and explain

why it is reversible.

19.64 The meat tenderizer used in cooking is primarily papain, a

protease enzyme isolated from the fruit of the papaya tree.

Why do you suppose papain is so effective at tenderizing

meat?

19.65 Bumblebee venom contains several related heptadecapeptides from the bomditin family. Papain can be used to

help relieve the pain of bee stings. Why do you suppose it

works?



ENZYME REGULATION: ALLOSTERIC CONTROL AND FEEDBACK

(SECTION 19.7)

19.66 Why do allosteric enzymes have two types of binding

sites?

19.67 Discuss the purpose of positive and negative regulation.

19.68 What is feedback inhibition?

19.69 What are the cellular advantages to feedback inhibition?



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