Chapter 23: Protein Turnover and Amino Acid Catabolism
Organisms derive their energy from fuels other than stored fuels.
In previous chapters, the catabolism of carbohydrates and fats have been discussed.
The authors explain in Chapter 23 the role of proteins in energy metabolism.
The supplies of proteins in excess of what is needed to provide biosynthetic precursors are degraded for energy or converted into fats orCarbohydrates, even though they are not stored as fuels per se.
The carbon skeletons of the surplus amino acids are transformed into acetyl CoA, pyruvate, or one of the citric acid cycle intermediates.
The chapter begins with a discussion of the process of ubiquination.
Half-life is determined by the N-terminal amino acid.
When tagged by ubiquitin, the proteosome carries out the degradation.
The ubiquitin can be recycled after the proteosome cleaves it off.
Once aProtein is cleaved into individual amino acids, the amino acids are incorporated into newly synthesized proteins or degraded to specific compounds for entry into an energy transduction pathway.
Nitrogen must be removed before entry into an energy transduction pathway can be considered a fate.
The a-amino groups of most acids are transferred to a-ketoglutarate and then converted to ammonia.
The authors talk about the reaction mechanism and role of the coenzyme pyridoxalphosphate.
The production of the citric acid cycle intermediate fumarate is linked to the urea cycle.
The catabolic pathways of the carbon skeletons are many and varied.
The authors describe how the carbon atoms of each amino acid are funneled into different products.
Two of these, acetyl CoA and acetoacetyl CoA, can be converted to ketone bodies, and the remaining five can be converted into glucose in energy-generating pathways.
There are two groups of products that lead to the classification of the amino acids.
The chapter ends emphasizing the importance of carrying out catabolism by looking at the pathological consequences of defects or deficiencies in some of the enzymes involved in catabolism.
You should be able to complete the objectives once you have mastered this chapter.
State the fate of the exogenously supplied amino acids that are not used for synthesis.
Nitrogen metabolism and energy generation are linked by the participation of NAD+ in the reaction.
List the other reactions catalyzed by PLP and describe their features.
The urea cycle and the citric acid cycle have the same components.
The strategy for catabolizing the carbon atom skeletons of amino acids was used by humans.
The limitations of this classification are appreciated.
Garrod had a hypothesis about this disorder.
Surplus food may be converted into food products.
Transamination may result in the removal of a-amino groups for conversion to urea in animals.
The catabolic products in the right column can be derived from the left col umn.
The following are classified as glycogenic, ketogenic, or both.
The synthesis of the amino acids is done directly for those purposes.
The carbon skeletons of any in excess can be converted into acetyl CoA or glucose, depending on the particular amino acid, and thus into products that are derivable from these two basic molecules.
The correct order is e, b, d, f, a, and c.
Correct answers are (a) and (d).
A-ketoglutarate forms a-keto acids that can be catabolized.
Serine and threonine are deaminated by dehydratases that take advantage of the b-hydroxyl of these amino acids to carry out a dehydration followed by a rehydration to release NH + 4
In this case, e-ketoglutarate can be found in a five-carbon e-keto acid and a five-carbon e-keto acid can be found in a five-carbon e-keto acid and a five-carbon e-keto acid.
The other partner in the reaction, pyruvate, will make a product.
In transamination reactions, Pyridoxalphosphate acts as an amino carrier.
A carbon-nitrogen double bond between the a-amino group of the lysine and a carbon of PLP is what it is bound to.
The aldimine bond is formed by the displacement of the e-amino group of the lysine of the enzyme.
The carbon-nitrogen bond isomerized to a ketimine through a deprotonation and a reprotonation.
The addition of H2O to the ketimine releases the carbon skeleton of the a-keto acid and leaves the coenzyme in the pyridoxamine form.
After the dissociation of the a-keto acid, a different a-keto acid binding to the a-keto acid causes it to form a new ketimine.
Uracil is not a nitrogen excretory component.
Uric acid is produced by uricotelic organisms.
There are three moles involved in the synthesis of urea.
One is converted to PPi by argininosuccinate synthesizer and two are converted to Pi by the same synthesizer.
A total of four high-energy bonds are used to convertAMP back intoATP.
Only one molecule of nitrogen enters as NH + 4 and the other enters in the a-amino group of aspartate, which can be formed by a transamination between oxaloacetate and glutamate.
One of the two direct donors of nitrogen would appear to be the a-amino group of alanine.
The a-amino groups can be collected on aspartate and fed into the cycle.
The urea molecule is constructed by Ornithine.
The ornithine group has a group added to it by ornithine transcarbamoylase.
The second nitrogen atom and ornithine can be regenerated when arginase cleaves arginine to form urea.
The NH + 4 concentrations would be increased if there was a defect in the synthesis of carbamoyl phosphate.
If a pathway is blocked at any of its steps, it may lead to increased concentrations of members of the pathway.
Both of them give rise to methylmalonyl CoA, which can be converted into succinyl CoA.
Monoxygenases and dioxygenases are involved in the conversion of phenylalanine to tyrosine and the opening of the aromatic ring during tyrosine catabolism.
The answers are correct.
There is an absence or deficiency in the cofactor of the phenylalanine hydroxylase.
It results in a build-up of phenylalanine in the body and is treated with a diet low in phenylalanine.
The attachment of ubiquitin to E1, E2, and E3 requires three enzymes.
Give a description of the role of the enzyme in ubiquitin attachment.
Birds need arginine in their diet.
A male infant six weeks of age exhibited symptoms of hyperammone mia, which included vomiting, fever, and screaming episodes, as well as periods of lethargy.
The infant had low levels of blood urea.
The levels of citrulline, argininosuccinic acid, and arginine were low in both urine and blood.
The urea cycle enzyme levels were normal.
The infant was treated with a supplement containing some of the essential acids that can't be synthesised in humans.
As part of the therapy, it was restricted.
During the process of glomerular filtration in the kidneys, amino acids and other substances enter the tubule.
Normally, a large portion of these amino acids are reabsorbed into the blood through the action of carrier systems that are specific for different classes of amino acids.
The symptoms of cystinuria include high concentrations of cystine as well as excess amounts of ornithine, lysine, and arginine.
There are two cysteine molecules and a disulfide linkage in cystine.
Patients with this disorder often have stones in their urinary tract.
The appearance of ornithine, lysine, and arginine in the urine is a symptom of a related disorder found in other people.
There is an increase in the concentrations of the amino acid in the blood and in the glomerular filtrate.
In this case, the capacity of the reabsorption system is not enough to absorb all of the urine.
Brain cells take up tryptophan, which is converted to 5-Hydroxytryptophan by tryp tophan hydroxylase, an activity that is similar to that of phenylalanine hydroxylase.
About 10% of the blood's tryptophan is free to be diffused.
Concentration of free tryptophan is a factor that affects the rate of tryptophan being taken by brain cells.
Aspirin and other drugs increase the concentration of free tryptophan.
The catabo lism of glutamate is caused by generating ammonia and a-ketoglutarate, which oxidize in the citric acid cycle.
In order for the cell to grow in glutamate, aspartase is needed to remove ammonia from aspartate to form fumarate.
There is a pathway for the catabolism of glutamate.
The blood contains a number of the amino acids alanine, glutamate, and glutamine.
The removal of pyridoxal phos phate from the enzyme can be accomplished with the use of a purification method, but the dissociation of the cofactor is very slow.
In some experiments, free pyridoxal was heated with amino acids like glutamate.
The pyridoxal was generated by the transfer of the (-amino group of glutamate.
A small number of infants with phenylketonuria have normal levels of phenylala nine hydroxylase activity, but on normal diet they accumulate phenylalanine and other metabolites.
They have high levels of quinonoid dihydrobiopterin.
Rationalize the deficiency with the symptoms.
Adenylates ubiquitin on its terminal carboxylate with the release of PPi.
A thioester bond is formed when ubiquitin is transferred to a sulfhydryl.
E2 gets ubiquitin from E1.
Ubiquitin is bound to E2 via a thioester bond.
The ubiquitin-protein ligase transfers ubiquitin from E2 to the e-amino group.
In the urea cycle, arginine is cleaved to yield urea and ornithine.
The fact that birds need arginine in their diet shows that they can't synthesise it.
They can't make urea to dispose of ammonia because they can't make uric acid.
The formation of pyrimidine is accomplished by using the activity of the bird's carbamoylphosphate synthesizer, which is located in the cytosol.
The urea cycle is affected by fumarase activity because it is needed for the regeneration of oxaloacetate, which undergoes transamination to form aspartate.
One of the nitrogen atoms is used to synthesise urea.
One of the ways that a-ketoglutarate can be used to generate glutamate is through the transfer of amino groups from one group to another.
Ammonia is needed for the urea cycle.
If all the other aminotransferases are active, then alanine would not be needed.
The rate of urea synthesis would be affected by a defect in fumarase activity.
The bacilli must carry out transamination reactions to dispose of ammonia as well as to generate a-keto if they want to use amino acids as sources of oxidative energy.
Inbacteria that can't be synthesised, Pyridoxalphosphate must be derived from the growth medium.
Amino acids can't be turned into something else.
If the only source of carbon and nitrogen is an amino acid, the bacilli will not be able to introduce it into any catabolic pathway.
Pyridoxalphosphate is a cofactor for a large number of other enzymes.
A large number of other pathways would be adversely affected by deficiencies in pyridoxalphosphate.
A deficiency in the activity of this enzyme causes ammonia to accumulate in blood and urine.
The rate of synthesis of other urea cycle components will be decreased when its synthesis is depressed.
In the urea cycle, arginine serves as an acceptor of the relatively small number of groups that enter the urea cycle.
In an attempt to drive the reaction catalyzed by the partially active CPS enzyme toward the net formation of carbamoyl phosphate, supplemental arginine synthesis could be accelerated.
acetyl glutamate is activated by CPS.
The rate of ammonia utilization is increased by supplying arginine.
Transamination takes place with glutamate as the donor.
More ammonia is used to remove some of it from the blood as a result of the increase in the synthesis of glutamate.
The transamination of the a-keto acids creates essential amino acids.
Chapter 23 contains information on the restriction of the diet with regard to the intake of food with regard to the amount of food with regard to the amount of food with regard to the amount of food with regard to the amount of food with regard to the amount of food with regard to the amount of Addingpyridoxine to the diet will ensure sufficient quantities to process the added a-keto analogs into essential amino acids.
The production of ammonia is affected by the breakdown of amino acids.
The therapy for this infant is to reduce the blood ammonia level.
The equilibria for most transamination reactions would be shifted to the net formation of other amino acids if the concentrations of glutamate were high.
Concentrations of these and other acids would be increased in the urine.
The action of transaminases as well as the action of GDH causes the deamination of amino acids.
GDH is the only one that can deamination an L acid.
A-ketoglutarate is the ultimate acceptor of most of the amino acids.
The GDH reaction is a logical activity to control because large changes in its velocity can be achieved with small changes in the concentrations of allosteric effectors.
The control of ammonia synthesis can be done with GDH.
The carrier systems are likely to recognize and bind these groups.
All four dibasic acids can spill over into the urine if the reabsorption of all four species fails.
The appearance of cystine in the urine is due to the failure of another system to function.
A defect in the carrier system means that all the amino acids in it will be lost to the urine.
Their concentration in blood and urine will be different.
It is said that Acetyl CoA can be utilized for the net synthesis of fat, but it cannot be used for the net synthesis of sugar.
In contrast to acetyl CoA, propionyl CoA can be used to give the net formation of glucose through the gluconeogenic pathway.
The difference between the two types is not obvious.
Succinyl CoA can be converted via pyruvate and acetyl CoA to citrate, which serves as the source of carbons for the synthesis of fatty acids.
Under certain conditions, glucogenic substrates can be ketogenic, but they cannot be glucogenic unless a cell has a functional glyoxylate pathway.
The cofactor is involved in the decarboxylation of 5-hydroxytryptophan by the aromatic acid decarboxylase.
A reduction in the rate of synthesis of serotonin is caused by a deficiency of vitamins B6 and B6.
The cells have more M tryptophan in them.
The level of 5-hydroxytryptophan production is expected to increase.
oxaloacetate is used to transamination to generate a-ketoglutarate and aspartate.
In the citric acid cycle, aspartate is cleaved to yield ammonia and fumarate.
Fumarate is converted to malate in the citric acid cycle so that it can be regenerated to serve as an acceptor of the glutamate group.
It should be noted that glutamate will be used as a source of amino groups by the enzymes involved in biosynthesis.
In cells grown in ammonia, GDH uses a-ketoglutarate to yield glutamate, which is a source of amino groups for other biosynthetic reactions.
The carbon from alanine, glutamate, and glutamine is utilized in the liver.
Glutamine is used to make ammonia and glutamate.
ammonia and a-ketoglutarate are formed by the oxidation of glutamate.
oxaloacetate is a source of carbon for gluconeogenesis and is produced from the transamination of alanine and a-keto acid.
The synthesis of urea is accomplished by the conversion of the a-keto acids to ammonia.
A source of energy can be found in the blood of the muscle, where it can be returned through the blood.
The synthesis of urea can be done with the use of the amino acids as a means of contributing to the generation of glucose in the liver.
acetylglutamate is generated from acetyl CoA and glutamate.
A reduction in the availability of the molecule will lead to a decrease in the activity of the molecule.
This leads to an increase in ammonia levels in blood and urine.
More than two-thirds of patients with methylmalonic aciduria are hyperammonemic.
The dissociation of the cofactor from the native enzyme is very slow because PLP is bound to a lysine residue.
The cofactor is no longer attached to the molecule after the addition of glutamate, which leads to the formation of a Schiff base.
The rate of dissociation of the cofactor from the enzyme is increased when PLP is bound by noncovalent forces.
It was suggested that pyridoxal is involved in transamination reactions by Snell's observations.
The a-keto group of an a-keto acid could be transferred from an a-amino group to the a-keto group.
The formation of pyridoxaminephosphate during the catalytic cycle is now established as a result of the action of pyridoxalphosphate.
There is a new Schiff base link with serine formed by PLP in the accompanying figure.
A hydrogen atom is removed from the a-carbon and the hydroxyl group is removed from the b-carbanion.
tautomerization to the imino form is followed by hydrolysis of the Schiff base.
This compound hydrolyzes to form ammonia and pyruvate.
PLP is linked to the enzyme again.
The reductant in the conversion of phenylalanine to tyrosine is called quinonoid dihydrobiopterin.
The reductase enzyme can be used for further use in tyrosine formation.
Cells that are deficient in the reductase can't convert phenylalanine to tyrosine.
In a similar way to the conversion of pyruvate to acetyl CoA, phenylacetate can be created by decarboxylation of phenylpyruvate.
The glucogenic route for aspartate involves transamination to oxaloacetate, which is then converted to a form of sugar.
PLP and NADH are involved in the conversion of aspartate to sugar.
The equation shows the synthesis of urea, the conversion of fumarate to oxaloacetate, and the hydrolysis of PPi.
The overall architecture could be compared to the 20S proteasome.
It is possible that the six different atoms of the 19S regulatory complex associate into a hexamer with pseudo six-fold symmetry.
If they could be separated from the 19S complexes, they might be visulaized by electron microscopy or crystallography.
It is an electron sink.
The answer in the text is to convert fumarate to oxaloacetate.
There is a non-energy-requiring transamination reaction.
The number of P spent is four.
Since aspartate is resynthesized, it does not appear in this equation.
Aspartate is a nitrogen carrying cofactor in the synthesis of urea.
The compound seems to be a non hydrolyzable analogue of an intermediate that should be formed between ornithine and carbamoylphosphate.
Ammonia could increase the ratio of asparatate/oxaloacetate and decrease the availability of all citric acid cycle intermediates.
The mass spectrometric analysis shows that three enzymes are deficient.
Most likely, the common E3 component is missing.
The proposal could be tested by purifying the three enzymes and finding out their capacity to regeneration.
There would be a restriction on the amount of Benzoate, phenylacetate, and arginine in the diet.
Nitrogen would come from hippurate, phenylacetylglutamine, and citrulline.
In the absence of urea synthesis, this therapy is designed to facilitate nitrogen excretion.
The nitrogen would be removed as glycine, glutamine, and citrulline.
L-as partate and L-phenylalanine are part of aspartame.
It is harmful to have high levels of phenylalanine.
acetylglutamate is made from acetyl CoA and glutamate.
acetyl CoA is an activated acetyl donor.
The first serine has a pyridoxal-5'-phos phate.
The b-OH can be eliminated if the serine a-hydrogen is removed.
The dehydration of citrate by aconitase is similar to the dehydration of these enzymes.
The D-serine or L-serine base can be given if the a-hydrogen is reattached from one of the faces.
The reaction will have an equilibrium constant.
Biological function is often related to the interaction of aprotein andprotein.
If an interaction domain becomes damaged so that interaction with a partner is no longer feasible, then it would be appropriate to turn over the protein.
mammals can't get food from fatty acids when carbohydrates are low.
The short-term demands of the brain for glucose are met by the small source of Glycerol.
Many of the energy needs of the brain can be provided by fats.
Isoleucine can give its group to a-ketoglutarate in a transamination reaction and then be decarboxylated and dehydrogenated to form acyl-coA derivatives.
The carbon skeleton is split into acetylS-coA and propionyl-S-coA after further reactions.
The oxidation of odd-chain fatty acids has been discussed in the three subsequent steps for the conversion of propionyl-S-coA to succinyl-S-coA.
Both ADP and AMP-PNP are not effective in stimulating digestion.
The finding that the digestion is not stimulated by AMP-PNP suggests that it is required.