Chapter 21 Flashcards
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.
common metabolites
…: amino group removal
deamination
cells continuously synthesize proteins from and degrade them to …
amino acids
. Controlling a protein’s rate of ..is therefore as important to the cellular and organismal economy as is controlling its rate of ….
degradation ; synthesis
the most rapidly degraded enzymes all occupy…, whereas the relatively stable enzymes have nearly constant catalytic activities under..
important metabolic control points; all physiological conditions.
Lysosomes contain ∼50 hydrolytic enzymes, including a variety of proteases known as …
cathepsins
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 …
autophagy; nonselective
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
ubiquitin
Proteins are marked for degradation by covalently …
linking them to ubiquitin.
linking a protein to ubiquitin:
- In an ATP-requiring reaction, ubiquitin’s terminal carboxyl group is conjugated, via a thioester bond, to… (E1).
- The ubiquitin is then transferred to a specific Cys sulfhydryl group on one of numerous homologous proteins named … (E2s
ubiquitin-activating enzyme
ubiquitin-conjugating enzymes
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.
Ubiquitin-protein ligase
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.
N-terminal residues; N-end rule
, 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.
PEST proteins,
proteins known as …that control the progression of the cell cycle are selectively degraded through their ubiquitination at specific stages of the cell cycle
cyclins
reversible …controls the activities of certain proteins rather than their degradation, in much the same way that phosphorylation and dephosphorylation alter protein activity
monoubiquitination
all cells appear to contain proteases whose active sites are only available from the …to which access is controlled–> …
inner cavity of a hollow particle; self-compartmentalized proteases
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
transamination; α-ketoglutarate
the aminotransferase reaction occurs via a …
Ping Pong mechanism
(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.
transamination; base
(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
α-hydrogen; carbanion
(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.
hydrolyzed
(aminotransferase rxn) Stage II Converts an 𝛂-Keto Acid to an Amino Acid.
3′. PMP reacts with an α-keto acid to form a …
Schiff base.
(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
tautomerizes
(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…
transamination; amino acid
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 …
electron sink
The amino groups from most amino acids are consequently funneled into the formation of …and ….
glutamate; aspartate
…is the only amino acid that is not transaminated.
Lysine
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.
.deamination; glutamate dehydrogenase
the glutamate dehydrogenase reaction functions to eliminate amino groups from amino acids that undergo …reactions with …
transamination; α -ketoglutarate.
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.
urea cycle.
urea’s two nitrogen atoms are contributed by …and …, whereas its carbon atom comes from …
ammonia; aspartate; HCO3-
(five rxns of urea cycle) … acquires the first urea nitrogen atom
carbamoyl phosphate synthetase
(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
carbamoyl phosphate
(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
CPS I; CPS II
(five rxns of urea cycle) CPS I catalyzes irreversible rate limiting step of cycle:
- ATP activates HCO3- to form … and ADP
- Ammonia attacks carboxyphosphate, displacing phosphate to form … and Pi
- A second ATP phosphorylates carbamate to form … and ADP
carboxyphosphate
carbamate
carbamoyl phosphate
(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
channeling; intermediates
(five rxns of urea cycle) . Ornithine transcarbamoylase transfers the carbamoyl group of carbamoyl phosphate to …, yielding …
ornithine; citrulline
(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
argininosuccinate synthetase; two
(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
argininosuccinase
(five rxns of urea cycle) …is urea’s immediate precursor
Arginine
(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.
arginase; ornithine
(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
“high-energy” phosphate bonds.
Carbamoyl phosphate synthetase I, which catalyzes the first committed step of the urea cycle, is allosterically activated by …
N-acetylglutamate
…:, which are degraded to pyruvate, α-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate and are therefore glucose precursors
Glucogenic amino acids
…, which are broken down to acetyl-CoA or acetoacetate and can thus be converted to fatty acids or ketone bodies
Ketogenic amino acids
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 …
Lys and Leu.
Five amino acids—…, …, …, …, and …—are broken down to yield pyruvate
alanine cysteine glycine serine threonine
…is both glucogenic and ketogenic.
threonine
each enzyme binds its amino acid– PLP Schiff base adduct with the appropriate geometry for …
bond cleavage
Transamination of aspartate leads directly to …. Asparagine is also converted to oxaloacetate in this manner after its hydrolysis to aspartate by …
oxaloacetate; L-asparaginase
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
glutamate
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
propionyl-CoA
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 …
methylating agent
Degradation of the branched-chain amino acids isoleucine, leucine, and valine begins with three reactions that employ common enzymes (Fig. 21-21):
- Transamination to the corresponding ..
- Oxidative decarboxylation to the corresponding …
- Dehydrogenation by FAD to form a …
α-keto acid.
acyl-CoA.
double bond.
….(BCKDH), is a multienzyme complex that closely resembles the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes
Branched-chain 𝛂-keto acid dehydrogenase
tryptophan is degraded to … and …
alanine; acetoacetate
phenyalanine and tyrosine are degraded to … and …
fumarate; acetoacetate
…are compounds that contain the pteridine ring Like flavins, they participate in biological oxidation
Pterins
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 ….
plants; microorganisms; essential amino acids
The other amino acids, which can be synthesized by mammals from common intermediates, are termed …
nonessential amino acids
… should also be considered to be an essential nutrient.
preformed
α -amino nitrogen
Essential Amino acids: … --> in children …. … … … … … … … ...
arginine histidine isoleucine leucine lysine methionine phenylalanine threonine tryptophan valine
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.
species; carbohydrate ; lipid
All the nonessential amino acids except tyrosine are synthesized by simple pathways leading from one of four common metabolic intermediates:…, …, …., and …
pyruvate, oxaloacetate, α-ketoglutarate, and 3-phosphoglycerate.
Pyruvate, oxaloacetate, and α-ketoglutarate are the α-keto acids (the so-called carbon skeletons) that correspond to …, …, and …, respectively
alanine; aspartate; glutamate
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.
glutamine synthetase
…, each with its own binding site, control the activity of bacterial glutamine synthetase in a cumulative manner.
Nine allosteric feedback inhibitors
E. coli glutamine synthetase is covalently modified by …(addition of an AMP group) of a specifi c Tyr residue
adenylylation
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
uridylylated `
glutamate is the precursor of .., …, and …
proline; ornithine; arginine
Serine is formed from the glycolytic intermediate 3-phosphoglycerate in a three-reaction pathway (Fig. 21-31):
- Conversion of 3-phosphoglycerate’s 2-OH group to a .., yielding 3-phosphohydroxypyruvate, serine’s phosphorylated keto acid analog.
- Transamination of 3-phosphohydroxypyruvate to … .
- Hydrolysis of phosphoserine to ….
ketone; phosphoserine
serine
Serine participates in glycine synthesis in two ways:
- Direct conversion of serine to glycine by …in a reaction that also yields N5,N10-methylene-THF
- Condensation of the N5,N10-methylene-THF with CO2 and NH+ 4 by …
serine hydroxymethyltransferase
glycine synthase
tryptophan synthase active sites are joined by a … that is wide enough to permit the passage of the intermediate substrate, …
solvent-filled tunnel; indole
The indole intermediate presumably diff uses between the two…via the tunnel and hence does not escape to the solvent.
active sites
histidine biosynthesis includes an intermediate in … biosynthesis, 5-aminoimidazole-4-carboxamide ribonucleotide
purine
all of heme’s C and N atoms can be derived from …and …
acetate ; glycine
the … and … cells regulate heme biosynthesis
liver; erythroid cells
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
ALA synthase; hemin
In erythroid cells, heme exerts quite a diff erent eff ect on its biosynthesis. Heme induces, rather than represses, protein synthesis in …(immature erythrocytes
reticulocytes
heme degradation products are .. These result from conversing of bilirubin to … and …
excreted; urobilinogen; stercobilin
…(adrenaline), …, …, …(5-hydroxytryptamine), … (GABA), and …(at left) are hormones and/or neurotransmitters derived from amino acids
Epinephrine norepinephrine dopamine serotonin 𝛄-aminobutyric acid histamine
The various
…—dopamine, norepinephrine, and epinephrine—are related to catechol (at left) and are sequentially synthesized from tyrosine (
catecholamines
…is even less common; N2 is converted to metabolically useful forms by only a few strains of bacteria, called diazotrophs.
Nitrogen fi xation
Once N2 is fi xed, the nitrogen is …(incorporated) into biological molecules as amino groups that can then be transferred to other molecules
assimilated
Diazotrophs produce the enzyme …, which catalyzes the reduction of N2 to NH3
nitrogenase
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
ferredoxin
the Fe-protein functions in the same way as a G protein, in which nucleotide hydrolysis triggers a …
dissociation event
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
12
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.
8; 16; 20-30
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 …
nitrate; ammonia
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 ….
heterocysts; leghemoglobin
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:
glutamate synthase
the combined action of these glutamine synthetase and glutamate synthase assimilates fixed nitrogen (NH+ 4 ) into an organic compound (α-ketoglutarate) to …
produce an amino acid (glutamate).
The ammonia produced by the nitrogenase reaction and incorporated into amino acids is eventually recycled in the biosphere, as described by the…
nitrogen cycle
other organisms convert nitrate back to N2, which is known as …
denitrification
, 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−
ammonification
Intracellular proteins and extracellular proteins taken up by endocytosis are degraded by ….
lysosomal proteases
Proteins tagged by the addition of multiple copies of ubiquitin enter the barrel-shaped …, where they are digested into ~…-residue fragments.
proteasome; 8
The degradation of an amino acid almost always begins with the removal of its amino group in a PLP-facilitated…
transamination reaction.
Glutamate undergoes oxidative deamination to …
α-ketoglutarate
A nitrogen atom from ammonia (a product of the oxidative deamination of glutamate) and bicarbonate are incorporated into … for entry into the urea cycle.
carbamoyl phosphate
A second nitrogen atom introduced from …enters the cycle to produce urea for excretion.
aspartate
The rate-limiting step of this process is catalyzed by …
carbamoyl phosphate synthetase.
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.
glucose; ketone bodies; fatty acids
The cofactors involved in amino acid degradation include …, …, and …
PLP; tetrahydrofolate; biopterin
The nonessential amino acids are synthesized in all organisms using simple pathways with the starting materials …, …, …, and …
pyruvate; oxaloacetate; α-ketoglutarate; 3-phosphoglycerate.
The essential amino acids, which are made only in …and …, require more complicated pathways that vary among organisms.
plants ; microorganisms
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 ….
glycine ; succinyl-CoA; mitochondria; cytosol
Heme degradation products include …and …
urobilin; stercobilin
Various hormones and neurotransmitters are synthesized by the decarboxylation and hydroxylation of …, …, .., and …
histidine, glutamate, tryptophan, and tyrosine.
The five-electron oxidation of arginine yields the bioactive stable radical …
nitric oxide
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.
nitrogenase
Fixed nitrogen is incorporated into amino acids via the … and … reactions.
glutamine synthetase; glutamate synthase
