Chapter 21

Question 1

Excess dietary amino acids are not simply excreted but are converted to… that are precursors of glucose, fatty acids, and ketone bodies and are therefore metabolic fuels.

Answer 1

common metabolites

Question 2

…: amino group removal

Answer 2

deamination

Question 3

cells continuously synthesize proteins from and degrade them to …

Answer 3

amino acids

Question 4

. Controlling a protein’s rate of ..is therefore as important to the cellular and organismal economy as is controlling its rate of ….

Answer 4

degradation ; synthesis

Question 5

the most rapidly degraded enzymes all occupy…, whereas the relatively stable enzymes have nearly constant catalytic activities under..

Answer 5

important metabolic control points; all physiological conditions.

Question 6

Lysosomes contain ∼50 hydrolytic enzymes, including a variety of proteases known as …

Answer 6

cathepsins

Question 7

Lysosomes degrade substances that the cell takes up via endocytosis. They also recycle intracellular constituents that are enclosed within vesicles that fuse with lysosomes, a process called … In well-nourished cells, lysosomal protein degradation is …

Answer 7

autophagy; nonselective

Question 8

Protein breakdown in eukaryotic cells also occurs in an ATP-requiring process that is independent of lysosomes. This process involves .., a 76-residue monomeric protein named for its ubiquity and abundance

Answer 8

ubiquitin

Question 9

Proteins are marked for degradation by covalently …

Answer 9

linking them to ubiquitin.

Question 10

linking a protein to ubiquitin:

1. In an ATP-requiring reaction, ubiquitin’s terminal carboxyl group is conjugated, via a thioester bond, to… (E1).
2. The ubiquitin is then transferred to a specific Cys sulfhydryl group on one of numerous homologous proteins named … (E2s

Answer 10

ubiquitin-activating enzyme

ubiquitin-conjugating enzymes

Question 11

linking a protein to ubiquitin contd:
3. …(E3) transfers the activated ubiquitin from E2 to a Lys ε-amino group of a previously bound protein, thereby forming an isopeptide bond.

Answer 11

Ubiquitin-protein ligase

Question 12

the half-lives of many cytoplasmic proteins vary with the identities of their … via the so-called …: Proteins with the “destabilizing” N-terminal residues Asp, Arg, Leu, Lys, and Phe have half-lives of only 2 to 3 minutes, whereas those with the “stabilizing” N -terminal residues Ala, Gly, Met, Ser, Thr, and Val have half-lives of >10 hours in prokaryotes and >20 hours in eukaryotes.

Answer 12

N-terminal residues; N-end rule

Question 13

, it has long been known that proteins with segments rich in Pro (P), Glu (E), Ser (S), and Thr (T), the so-called … are rapidly degraded. It is now realized that this is because these PEST elements often contain phosphorylation sites that target their proteins for ubiquitination.

Answer 13

PEST proteins,

Question 14

proteins known as …that control the progression of the cell cycle are selectively degraded through their ubiquitination at specific stages of the cell cycle

Answer 14

cyclins

Question 15

reversible …controls the activities of certain proteins rather than their degradation, in much the same way that phosphorylation and dephosphorylation alter protein activity

Answer 15

monoubiquitination

Question 16

all cells appear to contain proteases whose active sites are only available from the …to which access is controlled–> …

Answer 16

inner cavity of a hollow particle; self-compartmentalized proteases

Question 17

Most amino acids are deaminated by …, the transfer of their amino group to an α-keto acid to yield the α-keto acid of the original amino acid and a new amino acid.The predominant amino group acceptor is…, producing glutamate and the new α-keto acid

Answer 17

transamination; α-ketoglutarate

Question 18

the aminotransferase reaction occurs via a …

Answer 18

Ping Pong mechanism

Question 19

(aminotransferase rxn) Stage I Converts an Amino Acid to an 𝛂-Keto Acid
The amino acid’s nucleophilic amino group attacks the enzyme–PLP Schiff base carbon atom in a …reaction to form an amino acid–PLP Schiff base (an aldimine), with concomitant release of the enzyme’s Lys amino group. This Lys is then free to act as a general …at the active site.

Answer 19

transamination; base

Question 20

(aminotransferase rxn) Stage I Converts an Amino Acid to an 𝛂-Keto Acid
The amino acid–PLP Schiff base tautomerizes to an α-keto acid–PMP Schiff base (a ketimine) by the active site Lys–catalyzed removal of the amino acid …and protonation of PLP atom C4′ via a resonance stabilized ….intermediate. This resonance stabilization facilitates the cleavage of the Cα—H bond

Answer 20

α-hydrogen; carbanion

Question 21

(aminotransferase rxn) Stage I Converts an Amino Acid to an 𝛂-Keto Acid
3. The α-keto acid–PMP Schiff base is ….to PMP and an α-keto acid.

Answer 21

hydrolyzed

Question 22

(aminotransferase rxn) Stage II Converts an 𝛂-Keto Acid to an Amino Acid.
3′. PMP reacts with an α-keto acid to form a …

Answer 22

Schiff base.

Question 23

(aminotransferase rxn) Stage II Converts an 𝛂-Keto Acid to an Amino Acid.
2′. The α-keto acid–PMP Schiff base …to form an amino acid– PLP Schiff base

Answer 23

tautomerizes

Question 24

(aminotransferase rxn) Stage II Converts an 𝛂-Keto Acid to an Amino Acid.
1′. The ε-amino group of the active site Lys residue attacks the amino acid– PLP Schiff base in a …reaction to regenerate the active enzyme–PLP Schiff base and release the newly formed…

Answer 24

transamination; amino acid

Question 25

Note that removal of the substrate amino acid’s α-proton produces a resonance-stabilized Cα carbanion whose electrons are delocalized all the way to the coenzyme’s protonated pyridinium nitrogen atom; that is, PLP functions as an ...

Answer 25

electron sink

Question 26

The amino groups from most amino acids are consequently funneled into the formation of ...and ....

Answer 26

glutamate; aspartate

Question 27

...is the only amino acid that is not transaminated.

Answer 27

Lysine

Question 28

Transamination, of course, does not result in any net ... Glutamate, however, can be oxidatively deaminated by ... (GDH), yielding ammonia and regenerating α-ketoglutarate for use in additional transamination reactions.

Answer 28

.deamination; glutamate dehydrogenase

Question 29

the glutamate dehydrogenase reaction functions to eliminate amino groups from amino acids that undergo ...reactions with ...

Answer 29

transamination; α -ketoglutarate.

Question 30

Urea is synthesized in the liver by the enzymes of the ... It is then secreted into the bloodstream and sequestered by the kidneys for excretion in the urine.

Answer 30

urea cycle.

Question 31

urea’s two nitrogen atoms are contributed by ...and ..., whereas its carbon atom comes from ...

Answer 31

ammonia; aspartate; HCO3-

Question 32

(five rxns of urea cycle) … acquires the first urea nitrogen atom

Answer 32

carbamoyl phosphate synthetase

Question 33

(five rxns of urea cycle) carbamoyl phosphate synthetase catalyzes the condensation and activation of ammonia and HCO3- to form …, the first of the cycle's two nitrogen-containing substrates, with the concomitant cleavage of 2 ATP

Answer 33

carbamoyl phosphate

Question 34

(five rxns of urea cycle) Mitochondrial... uses ammonia as its nitrogen donor and participates in urea biosynthesis, whereas cytosolic ...uses glutamine as its nitrogen donor and is involved in pyrimidine biosynthesis

Answer 34

CPS I; CPS II

Question 35

(five rxns of urea cycle) CPS I catalyzes irreversible rate limiting step of cycle: 1. ATP activates HCO3- to form … and ADP 2. Ammonia attacks carboxyphosphate, displacing phosphate to form … and Pi 3. A second ATP phosphorylates carbamate to form … and ADP

Answer 35

carboxyphosphate carbamate carbamoyl phosphate

Question 36

(five rxns of urea cycle) This phenomenon, in which the intermediate of two reactions is directly transferred from one enzyme active site to another, is called .... It increases the rate of a metabolic pathway by preventing the loss of its … as well as protecting them from degradation

Answer 36

channeling; intermediates

Question 37

(five rxns of urea cycle) . Ornithine transcarbamoylase transfers the carbamoyl group of carbamoyl phosphate to ..., yielding ...

Answer 37

ornithine; citrulline

Question 38

(five rxns of urea cycle) Urea’s second nitrogen atom is introduced by the condensation of citrulline’s ureido group with an aspartate amino group by … The PPi formed in the reaction is hydrolyzed to 2 Pi, so the reaction consumes ...ATP equivalents

Answer 38

argininosuccinate synthetase; two

Question 39

(five rxns of urea cycle) With the formation of argininosuccinate, all of the urea molecule components have been assembled. However, the amino group donated by aspartate is still attached to the aspartate carbon skeleton. This situation is remedied by the ...catalyzed elimination of fumarate, leaving arginine

Answer 39

argininosuccinase

Question 40

(five rxns of urea cycle) ...is urea’s immediate precursor

Answer 40

Arginine

Question 41

(five rxns of urea cycle) The urea cycle’s final reaction is the ...catalyzed hydrolysis of arginine to yield urea and regenerate …, which is then returned to the mitochondrion for another round of the cycle.

Answer 41

arginase; ornithine

Question 42

(five rxns of urea cycle) The urea cycle thus converts two amino groups, one from ammonia and one from aspartate, and a carbon atom from HCO− 3 to the relatively nontoxic product, urea, at the cost of four … The energy spent is more than recovered, however, by the oxidation of the carbon skeletons of the amino acids that have donated their amino groups, via transamination, to glutamate and aspartate

Answer 42

“high-energy” phosphate bonds.

Question 43

Carbamoyl phosphate synthetase I, which catalyzes the first committed step of the urea cycle, is allosterically activated by ...

Answer 43

N-acetylglutamate

Question 44

…:, which are degraded to pyruvate, α-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate and are therefore glucose precursors

Answer 44

Glucogenic amino acids

Question 45

..., which are broken down to acetyl-CoA or acetoacetate and can thus be converted to fatty acids or ketone bodies

Answer 45

Ketogenic amino acids

Question 46

Since animals lack any metabolic pathways for the net conversion of acetyl-CoA or acetoacetate to gluconeogenic precursors, no net synthesis of carbohydrates is possible from the purely ketogenic amino acids … and ...

Answer 46

Lys and Leu.

Question 47

Five amino acids—..., ..., ..., ..., and ...—are broken down to yield pyruvate

Answer 47

``` alanine cysteine glycine serine threonine ```

Question 48

...is both glucogenic and ketogenic.

Answer 48

threonine

Question 49

each enzyme binds its amino acid– PLP Schiff base adduct with the appropriate geometry for ...

Answer 49

bond cleavage

Question 50

Transamination of aspartate leads directly to .... Asparagine is also converted to oxaloacetate in this manner after its hydrolysis to aspartate by ...

Answer 50

oxaloacetate; L-asparaginase

Question 51

Arginine, glutamine, histidine, and proline are all degraded by conversion to ...(Fig. 21-17), which in turn is oxidized to α-ketoglutarate by glutamate dehydrogenase

Answer 51

glutamate

Question 52

Methionine, threonine, isoleucine, and valine have degradative pathways that all yield ..., which is also a product of odd-chain fatty acid degradation. Propionyl-CoA is converted to succinyl-CoA by a series of reactions requiring biotin and coenzyme B12

Answer 52

propionyl-CoA

Question 53

Methionine degradation begins with its reaction with ATP to form S-adenosylmethionine (SAM; alternatively AdoMet). This sulfonium ion’s highly reactive methyl group makes it an important biological ...

Answer 53

methylating agent

Question 54

Degradation of the branched-chain amino acids isoleucine, leucine, and valine begins with three reactions that employ common enzymes (Fig. 21-21): 1. Transamination to the corresponding .. 2. Oxidative decarboxylation to the corresponding … 3. Dehydrogenation by FAD to form a ...

Answer 54

α-keto acid. acyl-CoA. double bond.

Question 55

….(BCKDH), is a multienzyme complex that closely resembles the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes

Answer 55

Branched-chain 𝛂-keto acid dehydrogenase

Question 56

tryptophan is degraded to … and ...

Answer 56

alanine; acetoacetate

Question 57

phenyalanine and tyrosine are degraded to … and ...

Answer 57

fumarate; acetoacetate

Question 58

...are compounds that contain the pteridine ring Like flavins, they participate in biological oxidation

Answer 58

Pterins

Question 59

Many amino acids are synthesized by pathways that are present only in ...and .... Since mammals must obtain these amino acids in their diets, these substances are known as ....

Answer 59

plants; microorganisms; essential amino acids

Question 60

The other amino acids, which can be synthesized by mammals from common intermediates, are termed ...

Answer 60

nonessential amino acids

Question 61

... should also be considered to be an essential nutrient.

Answer 61

preformed | α -amino nitrogen

Question 62

``` Essential Amino acids: … --> in children …. … … … … … … … ... ```

Answer 62

``` arginine histidine isoleucine leucine lysine methionine phenylalanine threonine tryptophan valine ```

Question 63

pathways for the essential amino acids as they occur in plants and microorganisms. Keep in mind that there is considerable variation in these pathways among different .... In contrast, the basic pathways of ...and ...metabolism are all but universal.

Answer 63

species; carbohydrate ; lipid

Question 64

All the nonessential amino acids except tyrosine are synthesized by simple pathways leading from one of four common metabolic intermediates:..., …, …., and ...

Answer 64

pyruvate, oxaloacetate, α-ketoglutarate, and 3-phosphoglycerate.

Question 65

Pyruvate, oxaloacetate, and α-ketoglutarate are the α-keto acids (the so-called carbon skeletons) that correspond to ..., ..., and ..., respectively

Answer 65

alanine; aspartate; glutamate

Question 66

Glutamine is the amino group donor in the formation of many biosynthetic products as well as being a storage form of ammonia. The control of ... is therefore vital for regulating nitrogen metabolism.

Answer 66

glutamine synthetase

Question 67

..., each with its own binding site, control the activity of bacterial glutamine synthetase in a cumulative manner.

Answer 67

Nine allosteric feedback inhibitors

Question 68

E. coli glutamine synthetase is covalently modified by ...(addition of an AMP group) of a specifi c Tyr residue

Answer 68

adenylylation

Question 69

Both adenylylation and deadenylylation of glutamine synthetase are catalyzed by adenylyltransferase in complex with a tetrameric regulatory protein, PII. This complex deadenylylates glutamine synthetase when PII is ...(also at a Tyr residue) and adenylylates glutamine synthetase when PII lacks UMP residues

Answer 69

uridylylated `

Question 70

glutamate is the precursor of .., …, and ...

Answer 70

proline; ornithine; arginine

Question 71

Serine is formed from the glycolytic intermediate 3-phosphoglycerate in a three-reaction pathway (Fig. 21-31): 1. Conversion of 3-phosphoglycerate’s 2-OH group to a .., yielding 3-phosphohydroxypyruvate, serine’s phosphorylated keto acid analog. 2. Transamination of 3-phosphohydroxypyruvate to … . 3. Hydrolysis of phosphoserine to ....

Answer 71

ketone; phosphoserine | serine

Question 72

Serine participates in glycine synthesis in two ways: 1. Direct conversion of serine to glycine by ...in a reaction that also yields N5,N10-methylene-THF 2. Condensation of the N5,N10-methylene-THF with CO2 and NH+ 4 by ...

Answer 72

serine hydroxymethyltransferase | glycine synthase

Question 73

tryptophan synthase active sites are joined by a … that is wide enough to permit the passage of the intermediate substrate, ...

Answer 73

solvent-filled tunnel; indole

Question 74

The indole intermediate presumably diff uses between the two...via the tunnel and hence does not escape to the solvent.

Answer 74

active sites

Question 75

histidine biosynthesis includes an intermediate in … biosynthesis, 5-aminoimidazole-4-carboxamide ribonucleotide

Answer 75

purine

Question 76

all of heme’s C and N atoms can be derived from ...and ...

Answer 76

acetate ; glycine

Question 77

the … and … cells regulate heme biosynthesis

Answer 77

liver; erythroid cells

Question 78

In liver, the main control target in heme biosynthesis is ...the enzyme catalyzing the pathway’s first committed step. Heme, or its Fe(III) oxidation product ..., controls this enzyme’s activity through feedback inhibition

Answer 78

ALA synthase; hemin

Question 79

In erythroid cells, heme exerts quite a diff erent eff ect on its biosynthesis. Heme induces, rather than represses, protein synthesis in ...(immature erythrocytes

Answer 79

reticulocytes

Question 80

heme degradation products are .. These result from conversing of bilirubin to … and ...

Answer 80

excreted; urobilinogen; stercobilin

Question 81

...(adrenaline), ..., ..., ...(5-hydroxytryptamine), ... (GABA), and ...(at left) are hormones and/or neurotransmitters derived from amino acids

Answer 81

``` Epinephrine norepinephrine dopamine serotonin 𝛄-aminobutyric acid histamine ```

Question 82

The various ...—dopamine, norepinephrine, and epinephrine—are related to catechol (at left) and are sequentially synthesized from tyrosine (

Answer 82

catecholamines

Question 83

...is even less common; N2 is converted to metabolically useful forms by only a few strains of bacteria, called diazotrophs.

Answer 83

Nitrogen fi xation

Question 84

Once N2 is fi xed, the nitrogen is ...(incorporated) into biological molecules as amino groups that can then be transferred to other molecules

Answer 84

assimilated

Question 85

Diazotrophs produce the enzyme ..., which catalyzes the reduction of N2 to NH3

Answer 85

nitrogenase

Question 86

Nitrogen fi xation by nitrogenase requires a source of electrons. These are generated either oxidatively or photosynthetically, depending on the organism. The electrons are transferred to ..., a [4Fe–4S]-containing electron carrier that transfers an electron to the Fe-protein of nitrogenase, beginning the nitrogen fixation process

Answer 86

ferredoxin

Question 87

the Fe-protein functions in the same way as a G protein, in which nucleotide hydrolysis triggers a ...

Answer 87

dissociation event

Question 88

An electron transfer must occur six times per N2 molecule fi xed, so a total of ... ATP are required to fi x one N2 molecule

Answer 88

12

Question 89

The total cost of N2 reduction is therefore ...electrons transferred and ... ATP hydrolyzed. Under cellular conditions, the cost is closer to ... ATP. Consequently, nitrogen fixation is an energetically expensive process.

Answer 89

8; 16; 20-30

Question 90

Although atmospheric N2 is the ultimate nitrogen source for all living things, most plants do not support the symbiotic growth of nitrogen-fi xing bacteria. They must therefore depend on a source of “prefi xed” nitrogen such as ...or ...

Answer 90

nitrate; ammonia

Question 91

Nitrogenase is rapidly inactivated by O2, so the enzyme must be protected from this reactive substance. Cyanobacteria provide the necessary protection by carrying out nitrogen fixation in specialized cells called …which have Photosystem I but lack the O2-generating Photosystem II. In the root nodules of legumes, however, protection is afforded by the hemoglobin homolog ....

Answer 91

heterocysts; leghemoglobin

Question 92

The glutamine synthetase reaction requires the nitrogen-containing compound glutamate as a substrate. So what is the source of the amino group in glutamate? In bacteria and plants, but not animals, the enzyme ...converts α-ketoglutarate and glutamine to two molecules of glutamate:

Answer 92

glutamate synthase

Question 93

the combined action of these glutamine synthetase and glutamate synthase assimilates fixed nitrogen (NH+ 4 ) into an organic compound (α-ketoglutarate) to ...

Answer 93

produce an amino acid (glutamate).

Question 94

The ammonia produced by the nitrogenase reaction and incorporated into amino acids is eventually recycled in the biosphere, as described by the...

Answer 94

nitrogen cycle

Question 95

other organisms convert nitrate back to N2, which is known as ...

Answer 95

denitrification

Question 96

, nitrate is reduced to NH3 by plants, fungi, and many bacteria, a process called ...in which nitrate reductase catalyzes the two-electron reduction of nitrate to nitrite (NO−

Answer 96

ammonification

Question 97

Intracellular proteins and extracellular proteins taken up by endocytosis are degraded by ....

Answer 97

lysosomal proteases

Question 98

Proteins tagged by the addition of multiple copies of ubiquitin enter the barrel-shaped ..., where they are digested into ~...-residue fragments.

Answer 98

proteasome; 8

Question 99

The degradation of an amino acid almost always begins with the removal of its amino group in a PLP-facilitated...

Answer 99

transamination reaction.

Question 100

Glutamate undergoes oxidative deamination to ...

Answer 100

α-ketoglutarate

Question 101

A nitrogen atom from ammonia (a product of the oxidative deamination of glutamate) and bicarbonate are incorporated into ... for entry into the urea cycle.

Answer 101

carbamoyl phosphate

Question 102

A second nitrogen atom introduced from ...enters the cycle to produce urea for excretion.

Answer 102

aspartate

Question 103

The rate-limiting step of this process is catalyzed by ...

Answer 103

carbamoyl phosphate synthetase.

Question 104

The 20 “standard” amino acids are degraded to compounds that give rise either to ….or to ... or ...: pyruvate, α-ketoglutarate, succinyl-CoA, fumarate, oxaloacetate, acetyl-CoA, or acetoacetate.

Answer 104

glucose; ketone bodies; fatty acids

Question 105

The cofactors involved in amino acid degradation include ..., ..., and ...

Answer 105

PLP; tetrahydrofolate; biopterin

Question 106

The nonessential amino acids are synthesized in all organisms using simple pathways with the starting materials ..., ..., ..., and ...

Answer 106

pyruvate; oxaloacetate; α-ketoglutarate; 3-phosphoglycerate.

Question 107

The essential amino acids, which are made only in ...and ..., require more complicated pathways that vary among organisms.

Answer 107

plants ; microorganisms

Question 108

Amino acids are the precursors of various biomolecules. Heme synthesis begins with ...and ...derived from acetylCoA, and the porphyrin ring is built in a series of reactions that occur in the ...and the ....

Answer 108

glycine ; succinyl-CoA; mitochondria; cytosol

Question 109

Heme degradation products include ...and ...

Answer 109

urobilin; stercobilin

Question 110

Various hormones and neurotransmitters are synthesized by the decarboxylation and hydroxylation of ..., ..., .., and ...

Answer 110

histidine, glutamate, tryptophan, and tyrosine.

Question 111

The five-electron oxidation of arginine yields the bioactive stable radical ...

Answer 111

nitric oxide

Question 112

Nitrogen fixation in bacteria, which requires 8 electrons and at least 16 ATP, is catalyzed by ..., a multisubunit protein with redox centers containing Fe, S, and Mo.

Answer 112

nitrogenase

Question 113

Fixed nitrogen is incorporated into amino acids via the ... and ... reactions.

Answer 113

glutamine synthetase; glutamate synthase