Chapter 18 Amino Acid Acid Oxidation and and the Production of Urea &1*
Chapter 18 Amino Acid Oxidation and the Production of Urea
Multiple Choice Questions 1. Metabo Metabolic lic fates fates of amino amino groups groups Page Pages: s: !"# !"#! ! $iff ifficul icult% t%:: & Ans: ns: $ Which of these is not a a protease that acts in the small intestine?
A) B) C) D) E)
Chym Chymot otry ryps psin in Elas lastase tase Ente Entero rope pept ptid idas asee Secr Secret etin in Trypsin
&. Metabo Metabolic lic fates fates of amino amino groups groups Page: Page: ! $iffic $ifficult ult%: %: & Ans: Ans: A In the digestion of protein that occurs in the small intestine, hich en!yme is critical in the acti"ation of !ymogens?
A) B) C) D) E)
Entero Enteropep peptid tidase ase #e$o #e$o%i %ina nase se &apain &epsin Secretin
'. Metabo Metabolic lic fates fates of amino amino groups groups Page: Page: ! $iffic $ifficult ult%: %: & Ans: Ans: ( Which of the folloing is a !ymogen ! ymogen that can 'e con"erted to an endopeptidase that hydroly!es peptide 'onds ad(acent ad(acent to ys ys and Arg residues?
A) B) C) D) E)
Chymot Chymotry rypsin psinoge ogen n &epsin &eps &epsin inog ogen en Trypsin sin Try Trypsin psinog ogen en
). Metabo Metabolic lic fates fates of amino amino groups groups Page: Page: !! $iffic $ifficult ult%: %: & Ans: Ans: ( In amino acid cata'olism, the first reaction for many amino acids is a*n)+
A) B) C) D) E)
decar'o$y decar'o$ylatio lation n reuiring reuiring thiamine thiamine pyrophos pyrophosphate phate *T&&)hydro$y hydro$ylation lation reuiring reuiring .AD&# .AD&# and and / 0o$idati"e o$idati"e deaminati deamination on reuir reuiring ing .AD 1reduction reduction reuiri reuiring ng pyrido$a pyrido$all phosphate phosphate *&&)*&&)transamin transamination ation reuir reuiring ing pyrido$ pyrido$al al phosphate phosphate *&&)*&&)-
Chapter 18 Amino Acid Oxidation and the Production of Urea
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". Metabolic fates of amino groups Page: !! $ifficult%: & Ans: + The coen!yme reuired for all transaminations is deri"ed from+
A) B) C) D) E)
niacinpyrido$ine *"itamin B 2)ri'ofla"inthiamin"itamin B30-
. Metabolic fates of amino groups Page: !! $ifficult%: 1 Ans: $ The coen!yme in"ol"ed in a transaminase reaction is+
A) B) C) D) E)
'iotin phosphatelipoic acidnicotinamide adenine dinucleotide phosphate *.AD& 1)pyrido$al phosphate *&&)thiamine pyrophosphate *T&&)-
!. Metabolic fates of amino groups Page: !! $ifficult%: 1 Ans: $ Transamination from alanine to α4%etoglutarate reuires the coen!yme+
A) B) C) D) E)
'iotin.AD#.o coen!yme is in"ol"edpyrido$al phosphate *&&)thiamine pyrophosphate *T&&)-
8. Metabolic fates of amino groups Page: !! $ifficult%: 1 Ans: ( &yrido$al phosphate is a cofactor in this class of reactions+
A) B) C) D) E)
acetylationdesulfurationmethylationreductiontransamination-
,. Metabolic fates of amino groups Pages: !!#!8- 8* $ifficult%: & Ans: A Which of the folloing is not true of the reaction cataly!ed 'y glutamate dehydrogenase?
A) B) C) D) E)
It is similar to transamination in that it in"ol"es the coen!yme pyrido$al phosphate *&&).#51 is producedThe en!yme can use either .AD 1 or .AD& 1 as a cofactorThe en!yme is glutamate4specific, 'ut the reaction is in"ol"ed in o$idi!ing other amino acidsα 46etoglutarate is produced from an amino acid-
Chapter 18 Amino Acid Oxidation and the Production of Urea
1*. Metabolic fates of amino groups Pages: !#!8 $ifficult%: & Ans: C 7lutamate is meta'olically con"erted to α 4%etoglutarate and .# 51 'y a process descri'ed as+
A) B) C) D) E)
deaminationhydrolysiso$idati"e deaminationreducti"e deaminationtransamination-
11. Metabolic fates of amino groups Page: 8* $ifficult%: 1 Ans: $ The con"ersion of glutamate to an α 4%etoacid and .# 51+
A) B) C) D) E)
does not reuire any cofactorsis a reducti"e deaminationis accompanied 'y AT& hydrolysis cataly!ed 'y the same en!ymeis cataly!ed 'y glutamate dehydrogenasereuires AT&-
1&. Metabolic fates of amino groups Pages: 81- 8'- ,- ,8 $ifficult%: & Ans: ( Which of the folloing con"ersions reuire more than one step?
30859A) B) C) D) E)
Alanine → pyru"ate Aspartate → o$aloacetate 7lutamate → α −%etoglutarate &henylalanine → hydro$yphenylpyru"ate &roline → glutamate
3 and 5 3, 0, and 5 3, 8, and 9 0, 5, and 9 5 and 9
1'. itrogen excretion and the urea c%cle Page: 8& $ifficult%: 1 Ans: C :rea synthesis in mammals ta%es place primarily in tissues of the+
A) B) C) D) E)
'rain%idneyli"ers%eletal musclesmall intestine-
&1&
Chapter 18 Amino Acid Oxidation and the Production of Urea
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1). itrogen excretion and the urea c%cle Page: 8' $ifficult%: 1 Ans: $ Which su'stance is not in"ol"ed in the production of urea from .# 51 "ia the urea cycle?
A) B) C) D) E)
Aspartate AT& Car'amoyl phosphate ;alate /rnithine
1". itrogen excretion and the urea c%cle Page: 8' $ifficult%: 1 Ans: + Which of these directly donates a nitrogen atom for the formation of urea during the urea c ycle?
A) B) C) D) E)
Adenine Aspartate Creatine 7lutamate /rnithine
1. itrogen excretion and the urea c%cle Pages: 8'#8" $ifficult%: 1 Ans: ( Con"ersion of ornithine to citrulline is a step in the synthesis of+
A) B) C) D) E)
aspartatecarnitinepyru"atetyrosineurea-
1!. itrogen excretion and the urea c%cle Pages: 8'#8) $ifficult%: 1 Ans: + In the urea cycle, ornithine transcar'amoylase cataly!es+
A) B) C) D) E)
clea"age of urea to ammoniaformation of citrulline from ornithine and another reactantformation of ornithine from citrulline and another reactantformation of urea from argininetransamination of arginine-
18. itrogen excretion and the urea c%cle Pages: 8)#8 $ifficult%: 1 Ans: ( Which of the folloing statements is false in reference to the mammalian synthesis of urea?
A) B) C) D) E)
6re's as a ma(or contri'utor to the elucidation of the pathay in"ol"edThe amino acid arginine is the immediate precursor to ureaThe car'on atom of urea is deri"ed from mitochondrial #C/ 8 < The precursor to one of the nitrogens of urea is aspartateThe process of urea production is an energy4yielding series of reactions-
Chapter 18 Amino Acid Oxidation and the Production of Urea
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1,. itrogen excretion and the urea c%cle Pages: 8 $ifficult%: & Ans: ( Which of the folloing amino acids are essential for humans?
A) B) C) D) E)
alanine aspartic acid asparagine serine threonine
&*. itrogen excretion and the urea c%cle Page: 8 $ifficult%: & Ans: ( If a person=s urine contains unusually high concentrations of urea, hich one of the folloing diets has he or she pro'a'ly 'een eating recently?
A) B) C) D) E)
#igh car'ohydrate, "ery lo protein >ery high car'ohydrate, no protein, no fat >ery "ery high fat, high car'ohydrate, no protein >ery high fat, "ery lo protein >ery lo car'ohydrate, "ery high protein
&1. Path/a%s of amino acid degradation Page: 88 $ifficult%: & Ans: A Which of these amino acids can 'e directly con"erted into a citric acid cycle intermediate 'y transamination?
A) B) C) D) E)
glutamic acid serine threonine tyrosine proline
&&. Path/a%s of amino acid degradation Page: 88 $ifficult%: & Ans: A Which of these amino acids are both %etogenic and glucogenic?
30859A) B) C) D) E)
Isoleucine >aline #istidine Arginine Tyrosine
3 and 9 3, 8, and 9 0 and 5 0, 8, and 5 0, 5, and 9
Chapter 18 Amino Acid Oxidation and the Production of Urea
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&'. Path/a%s of amino acid degradation Pages: ,* $ifficult%: & Ans: $ Tetrahydrofolate *T#) and its deri"ati"es shuttle
A) B) C) D) E)
'eteen different su'strates-
electrons #1 acyl groups one car'on units .#0 groups
&). Path/a%s of amino acid degradation Pages: ,1#,& $ifficult%: & Ans: + The amino acids serine, alanine, and c ysteine can 'e cata'oli!ed to yield+
A) B) C) D) E)
fumaratepyru"atesuccinateα 4%etoglutaratenone of the a'o"e-
&". Path/a%s of amino acid degradation Page: ,& $ifficult%: & Ans: C Serine or cysteine may enter the citric acid cycle as acetyl4CoA after con"ersion to+
A) B) C) D) E)
o$aloacetatepropionatepyru"atesuccinatesuccinyl4CoA-
&. Path/a%s of amino acid degradation Pages: ,#,! $ifficult%: 1 Ans: C The human genetic disease phenyl%etonuria *&6:) can result from+
A) B) C) D) E)
deficiency of protein in the dietina'ility to cata'oli!e %etone 'odiesina'ility to con"ert phenylalanine to tyrosineina'ility to synthesi!e phenylalanineproduction of en!ymes containing no phenylalanine-
&!. Path/a%s of amino acid degradation Page: !*1 $ifficult%: 1 Ans: + In the human genetic disease maple syrup urine disease, the meta'olic defect in"ol"es+
A) B) C) D) E)
a deficiency of the "itamin niacino$idati"e decar'o$ylationsynthesis of 'ranched chain amino acidstransamination of an amino acidupta%e of 'ranched chain amino acids into li"er-
Chapter 18 Amino Acid Oxidation and the Production of Urea
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0hort Ans/er Questions &8. Metabolic fates of amino groups Pages: !"#! $ifficult%: ' Descri'e *'riefly) the role of *a) gastrin, *') pepsinogen, *c) cholecysto%inin, and *d) enteropeptidase in protein digestionAns: *a) The hormone gastrin stimulates secretion of #Cl and pepsinogen into the stomach@ *') pepsinogen, after its con"ersion to pepsin, 'egins protein degradation in the stomach@ *c) the hormone cholecysto%inin stimulates the secretion of the pancreatic !ymogens chymotrypsinogen, trypsinogen, and procar'o$ypeptidase into the small intestine@ *d) enteropeptidase is a proteolytic en!yme that acti"ates trypsinogen in the small intestine- Trypsin in turn acti"ates chymotripsinogen, procar'o$ypeptidases, proelastase, and trypsinogen itself&,. Metabolic fates of amino groups Pages: !"#!! $ifficult%: & In the treatment of dia'etes, insulin is gi"en intra"enously- Why cant this hormone, a small protein, 'e ta%en orally? Ans: irst, the 'iological acti"ity of insulin ould 'e destroyed 'y the lo p# of the gastric (uice and the proteases that act in the small intestine- urthermore, e"en if insulin escaped degradation in the intestine, it ould not enter the 'loodstream from the intestine@ the transport systems in the cells that line the intestinal lumen transport free amino acids, not intact proteins'*. Metabolic fates of amino groups Page: ! $ifficult%: 1 Define !ymogen and descri'e the role of one !ymogen in protein digestionAns: A !ymogen is an inacti"e form of an en!yme that can 'e acti"ated 'y proteolytic clea"age- The pancreatic en!ymes pepsinogen, chymotrypsinogen, trypsinogen, and procar'o$ypeptidases A and B are all inacti"e forms of proteases, hich are acti"ated 'y proteolytic clea"age after their release into the small intestine'1. Metabolic fates of amino groups Pages: !!#!8 $ifficult%: 1 Transamination reactions are cataly!ed 'y a family of en!ymes, all of hich reuire as a coen!yme- In the first step of a transamination, the coen!yme in the aldehyde form condenses ith the group of an amino acid to form a*n) Ans: pyrido$al phosphate *&&)@
α4amino@
Schiff 'ase *or imine or aldimine)
'&. Metabolic fates of amino groups Page: !! $ifficult%: 1 Dra the structures of reactants and products in the transamination in hich glutamate and pyru"ate are the starting materials- What cofactor is reuired for this reaction? Ans: The correct anser is the re"erse of the reaction shon in ig- 345, p- 2, ith F C# 8&yrido$al phosphate *&&) is the cofactor-
&1!
Chapter 18 Amino Acid Oxidation and the Production of Urea
''. Metabolic fates of amino groups Page: !! $ifficult%: 1 7i"e the name and dra the structure of the α 4%eto acid resulting hen the folloing amino acids undergo transamination ith α4%etoglutarate+ *a) aspartate@ *') alanineAns: *a) o$aloacetate@ *') pyru"ate@ see ig- 345, p- 2'). Metabolic fates of amino groups Page: !, $ifficult%: ' Descri'e, 'y shoing the chemical intermediates, the role of pyrido$al phosphate *&&) in the transamination of an amino acidAns: See the yello screened portion of ig- 342, p- 2G'". Metabolic fates of amino groups Pages: !,#8* $ifficult%: ' Descri'e the roles of glutamine synthetase and glutaminase in the meta'olism of amino groups in mammalsAns: In tissues that are meta'oli!ing the car'on s%eletons of a mino acids, the amino groups are transferred 'y transamination to glutamate, then released as ammonia- Ammonia, hich is to$ic, is then com'ined ith glutamate to form glutamine@ the reaction is cataly!ed 'y glutamine synthetase and reuires AT&- 7lutamine is mo"ed from the e$trahepatic tissues to the li"er and %idneys, here the amino group is released from glutamine 'y glutaminase@ the products are glutamate and ammoniaThe ammonia deli"ered in this ay to the li"er is con"erted to urea, then e$creted'. Metabolic fates of amino groups Page: 8* $ifficult%: 1 Sho the reaction in hich ammonia is f ormed from glutamate@ include any reuired cofactorsAns: This is the reaction cataly!ed 'y glutamate dehydrogenase@ see ig- 34, p- 2H'!. Metabolic fates of amino groups Pages: 81#8& $ifficult%: ' Descri'e the reactions and the role of the glucose4alanine cycleAns: To$ic ammonia formed 'y amino acid cata'olism in muscle is transported to the li"er as alanine, hich is nonto$ic- Alanine is formed in muscle 'y transamination of pyru"ate *formed 'y glycolysis)@ glutamate formed 'y glutamate dehydrogenase is the amino donor- In the li"er, alanine is recon"erted to pyru"ate 'y transamination- Its amino group is e"entually con"erted to urea, and the pyru"ate is con"erted to glucose 'y gluconeogenesis in the li"er, then e$ported to muscle'8. itrogen excretion and the urea c%cle Page: 8& $ifficult%: & Why does a mammal go to all of the trou'le of ma%ing urea from ammonia rather than simply e$creting ammonia as many 'acteria do? Ans: When 'acteria release ammonia into the surrounding medium, it is diluted enormously to nonto$ic le"els- The ammonia produced 'y amino acid cata'olism in mammals cannot 'e sufficiently diluted in the tissues and the 'lood to a"oid accumulating at to$ic le"els- :rea is much less to$ic than
Chapter 18 Amino Acid Oxidation and the Production of Urea
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ammonia',. itrogen excretion and the urea c%cle Page: 8& $ifficult%: 1 Descri'e the three general mechanisms for disposing of e$cess nitrogen o'tained in the diet- Which organisms use each mechanism? Ans: *3) Ammonotelic+ release into the surrounding medium as .# 51 *'acteria and many marine organisms)@ *0) :ricotelic+ production of uric acid *'irds and reptiles)@ *8) :reotelic+ production and e$cretion of urea *land4delling animals))*. itrogen excretion and the urea c%cle Page: 8' $ifficult%: ' Amino acid cata'olism in"ol"es the 'rea%don of 0H amino acids all of hich contain nitrogen 'ut ha"e different car'on s%eletons- What o"erall strategy is used to deal ith this pro'lem? Illustrate the strategy ith to e$amplesAns: .itrogen is remo"ed 'y transamination to glutamate- This con"erts the amino acid to an α 4%eto acid that either is an intermediate in car'ohydrate cata'olism or is con"erted to one- *See ig- 340, p- 29-) E$amples are shon in ig- 343H, p- 28)1. itrogen excretion and the urea c%cle Page: 8 $ifficult%: 1 During star"ation, more urea production occurs- E$plain this o'ser"ation *in 9H ords or less)Ans: During star"ation, cellular proteins are degraded and their car'on s%eletons are o$idi!ed for energy- The first step in amino acid cata'olism is remo"al of the amino groups, hich are ultimately e$creted as urea)&. itrogen excretion and the urea c%cle Pages: 8#8! $ifficult%: 1 Descri'e *a) the fundamental nutritional pro'lem faced 'y indi"iduals ith genetic defects in en!ymes in"ol"ed in urea formation and *') to approaches to treatment of these diseasesAns: *a) A defect in urea synthesis can result in the formation of to$ic 'lood le"els of ammonia from the 'rea%don of ingested proteins- Thus, it is desira'le to limit the inta%e of amino acids- #oe"er, some amino acids are essential for humans *i-e-, not 'iosynthesi!ed) and hence must 'e ingested in adeuate amounts- *') /ne approach is to administer compounds that deplete the supply of glycine and glutamine- The replenishment of these amino acids remo"es ammonia from the 'lood- Another approach is to administer compounds that allo the li"er to 'ypass the en! yme that is defecti"e in the indi"idual)'. Path/a%s of amino acid degradation Pages: 8!#88 $ifficult%: 1 .ame four amino acids that can 'e con"erted directly *in one step) into pyru"ate or a citric acid cycle intermediate, and name the intermediate formed from eachAns: *3) aspartate@ o$aloacetate@ *0) glutamate@ pyru"ate- */rder is not important-)
4%etoglutarate@ *8) alanine@ pyru"ate@ *5) serine@
α
Chapter 18 Amino Acid Oxidation and the Production of Urea
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)). Path/a%s of amino acid degradation Pages: 8!#88 $ifficult%: & .ame one amino acid hose o$idation proceeds "ia the intermediate shon+ *a) pyru"ate@ *') o$aloacetate@ *c) α 4%etoglutarate@ *d) succinyl4CoA@ *e) fumarateAns: &ossi'le ansers are+ *a) alanine, tryptophan, glycine, serine, cysteine@ *') aspartate, asparagine@ *c) glutamate, glutamine, arginine, histidine, proline@ *d) isoleucine, threonine, methionine, "aline@ *e) phenylalanine, tyrosine)". Path/a%s of amino acid degradation Pages: 8!#88 $ifficult%: & Degradation of amino acids yields compounds that are common intermediates in the ma(or meta'olic pathays- E$plain the distinction 'eteen glucogenic and %etogenic amino acids in terms of their meta'olic fatesAns: The glucogenic amino acids are those that are cata'oli!ed to intermediates that can ser"e as su'strates for gluconeogenesis+ pyru"ate and any of the four4 or fi"e4car'on intermediates of the citric acid cycle- 6etogenic amino acids are cata'oli!ed to yield acetyl4CoA or acetoacetyl4CoA, the precursors for %etone 'ody formation). Path/a%s of amino acid degradation Pages: ,1#,& $ifficult%: & There are 'acteria for hich alanine can ser"e as the chief energy source@ they o$idi!e the car'on s%eleton of this amino acid, there'y generating AT&- Descri'e the first step in alanine degradation@ sho any cofactors that participateAns: The first step is remo"al of the amino group 'y transamination, in hich pyrido$al phosphate *&&) ser"es as an essential cofactor and α4%etoglutarate is the usual amino group acceptor+ &&
Alanine 1 α 4%etoglutarate
pyru"ate 1 glutamate
)!. Path/a%s of amino acid degradation Pages: ,#,! $ifficult%: & If you recei"ed a la'oratory report shoing the presence of a high concentration of phenylalanine and its meta'olites in the urine of a patient, hat disease ould you suspect? What defect*s) in meta'olism account*s) for the accumulation of phenylalanine in such patients? Ans: &henyl%etonuria, the disease that results from a defect in either phenylalanine hydro$ylase or the en!yme that cataly!es regeneration of tetrahydro'iopterin-
Chapter 18 Amino Acid Oxidation and the Production of Urea
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)8. Path/a%s of amino acid degradation Pages: ,#,! $ifficult%: & Suppose you are responsi'le for formulating the diet for a 54year4old 'oy ith phenyl%etonuria- #o do you decide hat %ind and amount of protein to include in the diet? Ans: A groing child needs a certain amount of phenylalanine and tyrosine for the synthesis of ne proteins- Because an e$cess of phenylalanine and tyrosine is to$ic in phenyl%etonurics, the diet should include (ust enough of these amino acids in protein to supply these needs, 'ut not enough so that phenyl%etones 'egin to accumulate in the 'lood and urine- If the defect causing phenyl%etonuria lies in the en!yme that regenerates tetrahydro'iopterin, l48,54dihydro$yphenylalanine and 94 hydro$ytryptophan must also 'e supplied in the diet- Adding tetrahydro'iopterin to the diet ill not help 'ecause the compound is unsta'le and cannot cross the 'lood4'rain 'arrier),. Path/a%s of amino acid degradation Pages: ,8#,, $ifficult%: ' Diagram the degradati"e pathay from proline to an intermediate of either glycolysis or the citric acid cycle- Sho structures of intermediates and indicate here cofactors are in"ol"edAns: The shortest pathay is from proline to ∆34pyrroline494car'o$ylate, glutamate semialdehyde, glutamate, and α 4%etoglutarate- See ig- 3402, p- 2G-
