Chapter 18: Amino Acid Oxidation and the Production of Urea

Question 1

In animals, amino acids undergo oxidative degradation in three different metabolic circumstances

Answer 1

1. During normal synthesis and degradation of cellular proteins (protein turnover), some amino acids are released from protein breakdown and are not needed for new protein synthesis undergo oxidative degradation
2. Diet rich in protein and the ingested amino acids exceed the body’s needs for protein synthesis, the surplus is catabolized; amino acids cannot be stored
3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either unavailable or not properly utilized, cellular proteins are used as fuel

Question 2

• amino acids lose their amino groups to form _____ _____, the “carbon skeletons” of amino acids.
• The α-keto acids undergo oxidation to _____ and ______ provide three- and four-carbon units that can be converted by gluconeogenesis into _____
• the carbon skeletons of most amino acids find their way to the _____ _____ _____

Answer 2

• α-keto acids
• CO₂, H₂O, glucose
• citric acid cycle

Question 3

• Amino acids derived from dietary protein are the source of most _____ _____
• Most amino acids are metabolized in the _____.
• Some of the ammonia generated in this process is _____ and the excess is either _____ or converted to _____ or _____ _____ for excretion
• Excess ______ travels to the liver in the form of _____ _____ for conversion to the excretory form

Answer 3

• amino groups
• liver
• recycled, excreted, urea, uric acid
• ammonia, amino groups

Question 4

• Four amino acids play central roles in nitrogen metabolism:
• These particular amino acids are the ones most easily converted into citric acid cycle intermediates:

Answer 4

• glutamate → α-ketoglutarate
• glutamine → α-ketoglutarate
• alanine → pyruvate
• aspartate → oxaloacetate

Question 5

Glutamate and glutamine are especially important because

Answer 5

• they act as a kind of general collection point for amino groups
• hepatocytes (liver cells)
  
  • amino groups in the cytosl from most amino acids are transferred to α-ketoglutarate to form glutamate
  • glutamate enters mitochondria and gives up its amino group to form NH₄⁺
• extrahepatic (situated or originating outside the liver)
  
  • Excess ammonia is converted to the amide nitrogen of glutamine
  • Glutamine passes to the liver and into mitochondria
• present in higher concentrations than other amino acids

Question 6

• In skeletal muscle, excess amino groups are generally transferred to pyruvate to form _____, important in the transport of amino groups to the liver
• _____ comes into play in the metabolic processes that occur once the amino groups are delivered to the liver

Answer 6

• alanine
• aspartate

Question 7

Dietary Protein Degradation to Amino Acids

Answer 7

• Entry of dietary protein into the stomach stimulates gastric mucosa to secrete the hormone gastrin
• Gastrin stimulates secretion of
  
  • hydrochloric acid by parietal cells
    
    • acidic gastric juice is an antiseptic and a denaturing agent
    • renders internal peptide bonds more accessible to enzymatic hydrolysis
  • pepsinogen by chief cells of gastric glands
    
    • inactive precursor (zymogen) for pepsin
    • gets converted to pepsin by an autocatalytic cleavage (mediated by pepsinogen itself)
      
      • hydrolyzes proteins at peptide bonds on the amino-terminal side of the aromatic amino acid residues Phe, Trp, and Tyr
      • cleaves long polypeptide chains
• acidic stomach contents pass into the small intestine
• low pH triggers secretion of hormone secretin into blood
• Secretin stimulates pancreas to secrete bicarbonate into the small intestine
• bicarbonate neutralizes the gastric HCl, increasing the pH ≈ 7
• Arrival of amino acids in duodenum (upper part of intestine) causes release of hormone cholecystokinin into blood
• cholecystokinin stimulates secretion of several pancreatic enzymes/zymogens by exocrine cells of the pancreas
  
  • trypsinogen
    
    • converted to active form trypsin, by enteropeptidase
    • trypsin converts additional trypsinogen to trypsin
    • activates chymotrypsinogen, the procarboxypeptidases, and proelastase
  • chymotrypsinogen
    
    • converted to active form chymotrypsin
  • procarboxypeptidases A and B
    
    • converted to active form carboxypeptidases A and B
  • Pancreas protects itself/exocrine cells by
    
    • synthesis of inactive precursors to avoid destructive proteolytic attack
    • synthesis of pancreatic trypsin inhibitor to prevent premature production of active proteolytic enzymes
• Trypsin and chymotrypsin further hydrolyze the peptides produced by pepsin
  
  • all 3 have different amino acid specificities
• Degradation of short peptides in the small intestine is completed by other intestinal peptidases
• aminopeptidase
  
  • hydrolyzes successive amino-terminal residues from short peptides
• products of aminopeptidase are transported into epithelial cells lining the small intestine
• amino acids enter blood capillaries in the villi and travel to the liver
• In humans
  
  • animal source globular proteins are almost completely hydrolyzed to amino acids in the gastrointestinal tract
  • fibrous proteins are only partly digested
  • protein content of some plant foods is protected against breakdown by indigestible cellulose husks

Question 8

• first step in the catabolism of most L-amino acids is removal of the ______ _____ and transferred to the α-carbon atom of _____, leaving behind the _____ _____ analog of the amino acid
• catalized by _____ in transamination reactions where there is no no net deamination (loss of amino groups)
• transamination reactions collect the amino groups from different amino acids in the form of _____.
• glutamate functions as an amino group _____ for biosynthetic or excretion pathways eliminating nitrogenous waste products

Answer 8

• α-amino groups, α-ketoglutarate, α-keto acid
• aminotransferases (transaminases)
• L-glutamate
• donor

Question 9

aminotransferases

Answer 9

• different types
• specific for α-ketoglutarate (amino group acceptor) but differ in their specificity for the L-amino acid
• same reaction mechanism, that are freely reversible
• has an equilibrium constant of about 1.0 (ΔG’ ≈ 0 kJ/mol)
• have the same prosthetic group, pyridoxal phosphate (PLP)
  
  • coenzyme form of pyridoxine, or vitamin B₆
  • primary role is in the metabolism of molecules with amino groups
  • intermediate carrier of amino groups at the active site
  • undergoes reversible transformations
    
    • pyridoxal phosphate
      
      • aldehyde form
      • accepts amino group
    • pyridoxamine phosphate
      
      • aminated form
      • donates its amino group to an α-keto acid
      • covalently bound to the enzyme’s active site through an aldimine (Schiff base) linkage to the ε-amino group of a Lys residue
  • participates in a variety of reactions at the α, β, and γ carbons of amino acids
    
    • reactions at the α carbon
      
      • racemizations (converting L- and D-amino acids)
      • decarboxylations
      • transaminations
    • in all reactions
      
      • a bond to the α carbon of the substrate is broken
      • a proton or a carboxyl group is removed forming a highly unstable carbanion, but pyridoxal phosphate provides resonance stabilization

The process

• incoming amino acid binds to the active site
  
  • donates amino group to pyridoxal phosphate
  • departs as α-keto acid
• incoming a-keto acid then binds to the active site
  
  • accepts amino group from pyridoxamine phosphate
  • departs as an amino acid.

Question 10

• Glutamate Releases Its Amino Group As _____ in the Liver
• amino groups from many of the α-amino acids are collected in the liver in the form of _____
• In hepatocytes, glutamate is transported from the cytosol into mitochondria and undergoes ______ ______ catalyzed by L-glutamate dehydrogenase, present in the mitochondrial matrix
• L-glutamate dehydrogenase is the only enzyme that can use either _____ or _____ as the acceptor of reducing equivalents
• Glutamate dehydrogenase is _____ enzyme with six identical subunits, influenced by a complicated array of allosteric modulators such as:

Answer 10

• Ammonia
• L-glutamate
• oxidative deamination
• NAD+, NADP+
• allosteric, positive modulator ADP and the negative modulator GTP

Question 11

• The combined action of an aminotransferase and glutamate dehydrogenase is referred to as ______
• A few amino acids bypass the transdeamination pathway and undergo _____ _____ _____
• ______ formed from glutamate deamination can be used in the citric acid cycle and for glucose synthesis

Answer 11

• transdeamination
• direct oxidative deamination
• α-ketoglutarate

Question 12

• Ammonia is quite toxic to animal tissues thus it’s converted to a nontoxic compound before export from the ______ tissues into the blood and transport to the liver or kidneys.
• free ammonia produced in tissues is combined with _____ to yield _____ by glutamine synthetase

Answer 12

• extrahepatic
• glutamate, glutamine

Question 13

Ammonia transport in the form of glutamine

Answer 13

• catalized by glutamine synthetase
  
  • found in all organisms
  • In microorganisms, serves as an essential portal for the entry of fixed nitrogen into biological systems
• requires ATP
• occurs in two steps
• First, glutamate and ATP react to form ADP and a γ-glutamyl phosphate intermediate
• γ-glutamyl phosphate reacts with ammonia to produce glutamine and inorganic phosphate
• Glutamine
  
  • a nontoxic transport form of ammonia
  • normally present in blood in much higher concentrations than other amino acids
  • serves as a source of amino groups
  • transports ammonia in the bloodstream
• amide nitrogen is released as ammonium ion in the mitochondria by glutaminase which converts glutamine to glutamate and NH₄⁺

Question 14

• In the liver, the ammonia from all sources is disposed of by _____ _____
• Some of the glutamate produced in the glutaminase reaction may be further processed in the liver by ______ ______, releasing more ammonia and producing carbon skeletons for metabolic fuel. However, most glutamate enters the _______ reactions

Answer 14

• urea synthesis
• glutamate dehydrogenase, transamination

Question 15

Alanine plays a role in transporting amino groups to the liver in a nontoxic form, via a pathway called the ______ ______

Answer 15

• glucose-alanine cycle

Question 16

• alanine passes into the blood and travels to the liver. In the cytosol alanine aminotransferase transfers the amino group from alanine to α-ketoglutarate, forming _____ and _____
• Glutamate can then enter mitochondria, where the glutamate dehydrogenase reaction releases _____ or can undergo transamination with _____ to form _____, another nitrogen donor

Answer 16

• pyruvate, glutamate
• NH₄⁺, oxaloacetate, aspartate

Question 17

If not reused for the synthesis of new amino acids or other nitrogenous products, amino groups are channeled into a single ______ end product

Answer 17

excretory

Question 18

ammonotelic

Answer 18

• excreting amino nitrogen as ammon
• aquatic species

Question 19

ureotelic

Answer 19

• excreting amino nitrogen in the form of urea
• Most terrestrial animals

Question 20

uricotelic

Answer 20

• excreting amino nitrogen as uric acid
• birds and reptiles

Question 21

Plants recycle virtually all _____ _____—they excrete nitrogen only under very unusual circumstances

Answer 21

amino groups

Question 22

urea cycle

Answer 22

• biochemical reactions that produces urea (NH₂)₂CO from ammonia
• occurs in ureotelic organisms
• converts highly toxic ammonia to urea for excretion
• first metabolic cycle to be discovered, five years before the discovery of the TCA cycle.

Question 23

Urea production occurs almost exclusively in the ______ and is the fate of most of the ______ channeled there; it is then excreted into the _____

Answer 23

• liver
• ammonia
• urine

Question 24

Urea Cycle

Urea Is Produced from Ammonia in Five Enzymatic Steps

Answer 24

1. carbamoyl phosphate synthesis
   
   • amino group to enter the urea cycle is derived from ammonia in the mitochondrial matrix
   • NH₄⁺ together with CO₂ (as HCO₃^-) are used to form carbamoyl phosphate in matrix
     
     • functions as an activated carbamoyl group donor
   • catalyzed by carbamoyl phosphate synthetase I, a regulatory enzyme
   • requires ATP
2. Urea Cycle: First Stage
   
   • carbamoyl phosphate donates its carbamoyl group to ornithine to form citrulline, releasing P_i
   • catalyzed by ornithine transcarbamoylase
   • Ornithine
     
     • key intermediate in nitrogen metabolism
     • synthesized from glutamate in a five-step pathway
     • plays a role similar to oxaloacetate in citric acid cycle
     • accepts material at each turn of the urea cycle
   • citrulline passes from the mitochondrion to the cytosol
3. Urea Cycle: Second Stage
   
   • A condensation reaction between the amino group of aspartate and the ureido (carbonyl) group of citrulline forms argininosuccinate through a citrullyl-AMP intermediate
     
     • aspartate source was generated in mitochondria by transamination and transported into the cytosol
   • catalyzed by argininosuccinate synthetase
   • requires ATP
4. Urea Cycle: Third Stage
   
   • argininosuccinate is cleaved by argininosuccinase forming form free arginine and fumarate
   • fumarate is converted to malate before entering mitochondria to join the pool of citric acid cycle intermediates (only reversible step)
5. Urea Cycle: Fourth Stage
   
   • arginase cleaves arginine to yield urea and ornithine
   • Ornithine is transported into the mitochondrion to initiate another round of the urea cycle

PDF pg. 735-737

Question 25

Krebs bicycle

Answer 25

• Citric Acid and Urea Cycles are linked
• fumarate produced in the argininosuccinase reaction is also an intermediate of the citric acid cycle
• each cycle can operate independently
• Major transporters facilitate movement of malate and glutamate into the mitochondrial matrix and movement of aspartate and α-ketoglutarate out to the cytosol
  
  • malate–α-ketoglutarate transporter
  • glutamate-aspartate transporter
  • glutamate-OH– transporter
• Several enzymes of the citric acid cycle are also present as isozymes in the cytosol
• There’s no transporter to move fumarate generated in the cytosil back into the mitochondrial. However, fumarate can be converted to malate for transport into mitochondria
• aspartate-argininosuccinate shunt
  
  • Aspartate formed in mitochondria by transamination between oxaloacetate and glutamate can be transported to the cytosol, where it serves as nitrogen donor in the urea cycle reaction catalyzed by argininosuccinate synthetase.
• NADH produced by glycolysis, fatty acid oxidation, and other processes cannot be transported across the mitochondrial inner membrane
  
  • equivalents are brought in the mitochondrion by converting aspartate to oxaloacetate in the cytosol
  • oxaloacetate is reduced to malate with NADH
  • malate is transported into the mitochondria
  • Once inside malate is reconverted to oxaloacetate while generating NADH
  • oxaloacetate is converted to aspartate in the matrix and transported out of the mitochondrion
  • This malate-aspartate shuttle completes yet another cycle that functions to keep the mitochondrion supplied with NADH

PDF pg. 738

Question 26

Pathway Interconnections Reduce the Energetic Cost of Urea Synthesis

• considering the urea cycle in isolation, synthesis of one molecule of urea requires _____ high-energy phosphate groups
• ATP cost is ameliorated by the interconnections of the _____ _____ and _____ _____ ____
• During the Uric Cycle, malate is transported into the mitochondrion and _____ is generated in the malate dehydrogenase reaction
• Each NADH molecule can generate up to _____ ATP during mitochondrial respiration greatly reducing the overall energetic cost of urea synthesis.

Answer 26

• four
• Urea Cycle, Citric Acid Cycle
• NADH
• 2.5

Question 27

Pathways of Amino Acid Degradation

• pathways of amino acid catabolism are not nearly as _____ as glycolysis and fatty acid oxidation
• The 20 catabolic pathways converge to form only six major products, all of which enter the _____ ______ ______
• From the citric acid cycle​ the carbon skeletons are diverted to _____ or ______ or are completely oxidized to CO₂ and H₂O
• some amino acids have different fates for different parts of their ______ _____
• Only two amino acids, _____ and _____, are exclusively ketogenic

Answer 27

• active
• citric acid cycle
• gluconeogenesis, ketogenesis
• carbon skeletons
• leucine, lysine

Question 28

Some Amino Acids Are Converted to Glucose, Others to Ketone Bodies

ketogenic amino

• seven amino acids that are degraded to to acetoacetyl-CoA and/or acetyl-CoA:
• yield _____ _____
• Only two amino acids, _____ and _____, are exclusively ketogenic

glucogenic amino acids

• amino acids that are degraded to pyruvate, α-ketoglutarate, succinyl-CoA, fumarate, and/or oxaloacetate can be converted to _____ and _____
• they are:

both glucogenic and ketogenic

• division between ketogenic and glucogenic amino acids is not sharp; five amino acids are both:

Answer 28

ketogenic amino

• phenylalanine, tyrosine, isoleucine, leucine, tryptophan, threonine, and lysine
• ketone bodies
• leucine, lysine

glucogenic amino acids

• glucose, glycogen
• Alanine, Cysteine, Glycine, Serine, Threonine, Tryptophan, Asparagine, Aspartate, Glutamate, Arginine, Glutamine, Histidine, Proline, Isoleucine, Methionine, Valine, Phenylalanine, Tyrosine

both glucogenic and ketogenic

• tryptophan, phenylalanine, tyrosine, threonine, and isoleucine

Question 29

Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism

• common type of reaction in amino acid catabolism is _____ _____ transfers
• The one-carbon group undergoing transfer, in any of three oxidation states, is bonded to _____ or ____ or both
• this reaction involves one of three cofactors which transfer one-carbon groups in different oxidation states:
• Tetrahydrobiopterin is another cofactor that participates in

Answer 29

• one carbon
• N-5, N-10
• three cofactors
  
  • biotin
    
    • transfers carbon in its most oxidized state, CO₂
  • tetrahydrofolate
    
    • transfers groups in intermediate oxidation states and sometimes as methyl groups
    • synthesized in bacteria
    • converted in two steps to tetrahydrofolate by the enzyme dihydrofolate reductase
    • most reduced form carries a methyl group
    • more oxidized form carries a methylene group
    • most oxidized forms carry a methenyl, formyl, or formimino group
  • S-adenosylmethionine
    
    • transfers methyl groups, the most reduced state
    • preferred cofactor for biological methyl group transfers
    • synthesized from ATP and methionine by the action of methionine adenosyl transferase
    • transfer process
      
      • Transfer of methyl group from S-adenosylmethionine to an acceptor yields S-adenosylhomocysteine
      • S-adenosylhomocysteine is brokent down to homocysteine and adenosine
      • Methionine is regenerated by transfer of a methyl group to homocysteine catalyzed by methionine synthase
      • methionine is reconverted to S-adenosylmethionine
    • potent alkylating agent
• oxidation reactions

Question 30

Six Amino Acids Are Degraded to Pyruvate

1. carbon skeletons of six amino acids are converted to pyruvate and then to ______ and eventually oxidized via the citric acid cycle, or to ______ and shunted into ______
2. Alanine yields pyruvate directly on ______ with α-ketoglutarate, and the side chain of tryptophan is cleaved to yield _____ and thus ______
3. Cysteine is converted to pyruvate in two steps; one removes the sulfur atom, the other is a ______
4. Serine is converted to pyruvate by serine dehydratase. Both the ______ and the ______ groups of serine are removed in this single pyridoxal phosphate–dependent reaction
5. Glycine is degraded via three pathways, only one of which leads to pyruvate:
6. At high levels, glycine is an _____ _____
7. two significant pathways for threonine degradation

Answer 30

1. acetyl-CoA, oxaloacetate, gluconeogenesis
2. transamination , alanine, pyruvate
3. transamination
4. β-hydroxyl, α-amino
5. 3 pathways
   
   • Glycine is converted to serine by addition of a hydroxymethyl group catalyzed by serine hydroxymethyltransferase, requires the coenzymes tetrahydrofolate and pyridoxal phosphate
   • second pathway
     
     • predominates in animals
     • glycine undergoes oxidative cleavage to CO₂, NH₄⁺ and a methylene group
     • feversible reaction
     • catalyzed by glycine cleavage enzyme (glycine synthase)
       
       • requires tetrahydrofolate
       • the two carbon atoms of glycine do not enter the citric acid cycle
         
         • One carbon is lost as CO₂ and the other becomes the methylene group of N5,N10-methylenetetrahydrofolate
   • third pathway
     
     • achiral glycine molecule is a substrate for the enzyme D-amino acid oxidase
     • glycine is converted to glyoxylate
     • Glyoxylate is oxidized in an NAD⁺-dependent reaction to oxalate
6. inhibitory neurotransmitter
7. pathways
   
   • One pathway leads to pyruvate via glycine
   • occurs in two steps
     
     • threonine first converted to 2-amino- 3-ketobutyrate by the action of threonine dehydrogenase
   • major pathway in humans leads to succinyl-CoA and is described later.

Question 31

Seven Amino Acids Are Degraded to Acetyl-CoA

• Portions of the carbon skeletons of seven amino acids yield acetyl-CoA and/or acetoacetyl-CoA, the latter being converted to acetyl-CoA:
• ______ breakdown is the most complex of all the pathways of amino acid catabolism in animal tissues; portions of tryptophan (four of its carbons) yield acetyl-CoA via acetoacetyl-CoA.
• Some of the intermediates in _____ catabolism are precursors for the synthesis of other biomolecules, including nicotinate, a precursor of NAD and NADP in
• The breakdown of _____ is noteworthy because genetic defects in the enzymes of this pathway lead to several inheritable human diseases.
• Phenylalanine, after its hydroxylation to tyrosine, is also the precursor of _____, a neurotransmitter, and of ______ and _____

Answer 31

• tryptophan, lysine, phenylalanine, tyrosine, leucine, isoleucine, and threonine
• Tryptophan
• tryptophan
• phenylalanine
• dopamine, norepinephrine, epinephrine

Question 32

Given that many amino acids are either _____ or ______ or ______ of neurotransmitters, it is not surprising that genetic defects of amino acid metabolism can cause defective ______ development and intellectual deficits. In most such diseases specific intermediates accumulate

Answer 32

• neurotransmitters
• precursors
• antagonists
• neural

Question 33

Five Amino Acids Are Converted to α-Ketoglutarate

• carbon skeletons of five amino acids enter the citric acid cycle as α-ketoglutarate:
• Proline, glutamate, and glutamine conversion to ketoglutarate:
• Arginine and histidine conversion to ketoglutarate:

Answer 33

• proline, glutamate, glutamine, arginine, and histidine
• Proline, glutamate, and glutamine conversion to ketoglutarate
  
  • have five-carbon skeletons
  • cyclic structure of proline is opened by oxidation of the carbon most distant from the carboxyl group to create a Schiff base
  • Schiff base is hydrolized to glutamate γ-semialdehyde, a linear semialdehyde
  • This intermediate is oxidized at the same carbon to produce glutamate
  • Transamination or deamination of glutamate produces γ-ketoglutarate
• Arginine and histidine conversion to ketoglutarate
  
  • contain five adjacent carbons and a sixth carbon attached through a nitrogen atom
  • Arginine is converted to the five-carbon skeleton of ornithine in the urea cycle
    
    • ornithine is transaminated to glutamate γ-semialdehyde
  • Conversion of histidine to the five-carbon glutamate occurs in a multistep pathway
    
    • the extra carbon is removed in a step that uses tetrahydrofolate as cofactor

Question 34

Four Amino Acids Are Converted to Succinyl-CoA

• carbon skeletons of _____, ______, ______ and _____ are degraded by pathways that yield succinyl-CoA, an intermediate of the citric acid cycle
• propionyl-CoA derived from these three amino acids is converted to ______
• describe the breakdown of each

Answer 34

• methionine, isoleucine, threonine, and valine
• succinyl-CoA
• Methionine
  
  • donates methyl group to one of several possible acceptors through S-adenosylmethionine,
  • three of its four remaining carbon atoms are converted to the propionate of propionyl-CoA, a precursor of succinyl-CoA.
• Isoleucine
  
  • undergoes transamination
  • followed by oxidative decarboxylation of the resulting α-keto acid
  • remaining five-carbon skeleton is further oxidized to acetyl-CoA and propionyl-CoA
  • Some parts of the valine and isoleucine degradative pathways closely parallel steps in fatty acid degradation
• Valine
  
  • undergoes transamination and decarboxylation
  • then a series of oxidation reactions that convert the remaining four carbons to propionyl-CoA
  • Some parts of the valine and isoleucine degradative pathways closely parallel steps in fatty acid degradation
• threonine
  
  • in human tissues is also converted in two steps to propionyl-CoA
  • This is the primary pathway
  • The mechanism of the first step is analogous to that catalyzed by serine dehydratase
  • serine and threonine dehydratases may actually be the same enzyme

Question 35

Branched-Chain Amino Acids Are Not Degraded in the Liver

• much of the catabolism of amino acids takes place in the liver, the three amino acids with branched side chains ______, _____ and _____ are oxidized as fuels primarily in muscle, adipose, kidney, and brain tissue.
• These extrahepatic tissues contain an _______, absent in liver to produce the corresponding ______ _____
• branchedchain α-keto acid dehydrogenase complex then catalyzes oxidative decarboxylation of all three α-keto acids, in each case releasing the carboxyl group as _____ and producing the ______.
• This reaction is formally analogous to
• all three enzyme complexes are similar in structure and share essentially the same reaction mechanism and 5 cofactors:
• This clearly a case in which enzymatic machinery that evolved to catalyze one reaction was “borrowed” by _____ _____ and further evolved to catalyze similar reactions in other pathways

Answer 35

• leucine, isoleucine, and valine
• aminotransferase
• α-keto acids
• CO₂, acyl-CoA derivative
• oxidation of pyruvate to acetyl-CoA by the pyruvate dehydrogenase complex and oxidation of α-ketoglutarate to succinyl-CoA by the α-ketoglutarate dehydrogenase complex
• thiamine pyrophosphate, FAD, NAD, lipoate, and coenzyme A
• gene duplication

Question 36

Asparagine and Aspartate Are Degraded to Oxaloacetate

• carbon skeletons of asparagine and aspartate ultimately enter the citric acid cycle as ______ in mammals or ______ in bacteria
• The enzyme asparaginase catalyzes the hydrolysis of asparagine to ______, which undergoes transamination with α-ketoglutarate to yield ______ and ______
• The oxaloacetate is converted to ______ in the cytosol and then transported into the mitochondrial matrix through the malate–α-ketoglutarate transporter
• In bacteria, the oxaloacetate produced in the transamination reaction can be used directly in the _____ _____ _____

Answer 36

• malate, oxaloacetate
• aspartate, glutamate, oxaloacetate
• malate
• citric acid cycle