Nitrogen Elimination and Carbon Chain Metabolism I

Question 1

The free amino acids that are generated in the gut are mobilized by peptide transporters in intestinal epithelial cells, and delivered via the portal system to the

Answer 1

Liver

Question 2

In the liver, a family of related enzymes removes α-NH3 groups from amino acids and transfers them to an acceptor molecule, typically

Answer 2

α-ketoglutarate

Question 3

Transfer of α-NH3 to α-ketoglutarate results in the formation of

Answer 3

Glutamate

Question 4

While this first step does not alter the overall amount of nitrogen, it does reposition the nitrogen for more efficient elimination during the

Answer 4

Second stage

Question 5

In this second step, glutamate dehydrogenase can release nitrogen (as ammonia), which is then assimilated into

Answer 5

Urea

Question 6

After the removal of the alpha-amino group, carbon chains can be modified and channeled into the

-generates energy

Answer 6

TCA cycle

Question 7

The remnant carbon skeleton can also be stored, following their assimilation into

Answer 7

Fat and carbohydrates

Question 8

The carbon chain of amino acids can be used for generating energy, or stored as fat and carbohydrate after removal of the

Answer 8

Alpha-amino group

Question 9

Rarely coded in gene sequences, and this amino acid is underrepresented in proteins

Answer 9

Methionine

Question 10

Methionine is encoded by the single codon

Answer 10

ATG

Question 11

Degraded to yield amino acids, primarily in the gut, and absorbed by epithelial cells that line the intestine

Answer 11

Dietary Proteins

Question 12

Because the stability of cellular proteins can vary from seconds to years, their degradation is

Answer 12

Highly regulated

Question 13

Required for the uptake of amino acids in the gut, and their transfer to the portal system

-In the intestinal wall

Answer 13

Trans-membrane protein channels

Question 14

Help recover amino acids which are inadvertently released into the urine.

-Mutations in these pumps result in loss of amino acids which can cause amino acid deficiencies

Answer 14

Membrane channels in the kidney

Question 15

There are three primary sites where proteins are synthesized. These locations are termed

Answer 15

Gastric, pancreatic, and intestinal

Question 16

The function of the mouth/saliva is to masticate food so that it is easily transferred to the stomach. This initiates the first of three stages of

Answer 16

Proteolysis

Question 17

Generally named after critical residues in their active site

Answer 17

Proteases

Question 18

Proteases can also be named after a

Answer 18

Cofactor, substrate, or location

Question 19

The extreme acidity of the stomach begins protein unfolding and

Answer 19

Denaturation

Question 20

Digestive proteases are synthesized as inactive precursors, called

Answer 20

Zymogens

Question 21

The zymogen is catalytically inactivated by an inhibitory

-when removed, enzyme is activated

Answer 21

Prodomain

Question 22

Synthesized in intestinal mucosal cells, and its key function is to convert trypsinogen to active trypsin

Answer 22

Enteropeptidase

Question 23

Trypsin then activates the rest of the enzymes. This mechanism of autocatalytic protease activation is activated by hormonal signaling, and occurs primarily in the

Answer 23

Intestinal tract

Question 24

Secrete dipeptidases that can generate free amino acids

Answer 24

Intestinal cells

Question 25

Amino acid and dipeptide transporters take up amino acids/peptides into the intestinal cells, where we see complete

Answer 25

Peptide hydrolysis

Question 26

Free amino acids are transferred to the liver by the

Answer 26

Portal vein

Question 27

Proteases in the gut. These non-specific and potent enzymes are classified as

Answer 27

Endo- and exopeptidases

Question 28

These proteases are indiscriminate, because they degrade all, and not specific proteins

Answer 28

Endo- and exopeptidases

Question 29

May be either amino- or carboxypeptidases

Answer 29

Exopeptidases

Question 30

A serineprotease that cleaves after basic residues (lysine and arginine). -The hydroxyl group in serine contributes to the catalytic properties of this endopeptidase.

Answer 30

Trypsin

Question 31

The first step in amino acid breakdown involves the removal of the

Answer 31

Alpha amino group

Question 32

A family of aminotransferase enzymes transfers α-NH3 from most amino acids to

Answer 32

α-ketoglutarate

Question 33

Although this mechanism does not alter the balance in nitrogen (because net nitrogen level is unchanged), it provides an efficient way to concentrate all the

Answer 33

α-NH3 molecules on one or a few molecules

Question 34

The primary acceptor for NH3 in the liver, and most other tissues

Answer 34

α-ketoglutarate

Question 35

However, is generated and is to the liver in muscle cells (which produce abundant pyruvate)

Answer 35

Alanine (alanine = pyruvate + NH3)

Question 36

Are detected in the blood following a high protein meal because they provide a safe way to transfer excess NH3 to the liver for the synthesis of urea, and excretion in the urine

Answer 36

Alanine, Glutamine, and Asparagine

Question 37

Not transported in its free form because it is highly toxic to the central nervous system

Answer 37

Ammonia

Question 38

Can be released from glutamate via oxidative deamination to produce ammonia

Answer 38

NH3

Question 39

Oxidative deamination is mediated by -present in all tissues

Answer 39

Glutamate dehydrogenase

Question 40

Alternatively, α-ketoglutarate can enter the

Answer 40

TCA cycle

Question 41

The amino group can be transferred from glutamate to oxaloacetate by

Answer 41

Aspartate aminotransferase

Question 42

Both ammonia and aspartate provide a nitrogen in the assimilation of

Answer 42

Urea in the liver

Question 43

Can add NH3 to glutamate to increase the capture and transport of nitrogen (ammonia) from peripheral tissues to the liver

Answer 43

Glutamine Synthase

Question 44

Can add NH3 to aspartate (asparagine)

Answer 44

Asparagine synthesis

Question 45

Under conditions of ammonia toxicity, these reactions can rapidly sequester excess

Answer 45

NH3

Question 46

The transamination of pyruvate yields -can be safely transported to the liver

Answer 46

Alanine

Question 47

Alanine is converted back to pyruvate by transamination, and can then enter the pathway of

Answer 47

Gluconeogenesis

Question 48

The critical enzyme that initiates the net removal of nitrogen from amino acids (specifically glutamate)

Answer 48

Glutamate dehydrogenase

Question 49

Glutamate dehydrogenase is regulated by allosteric mechanisms. It is inhibited by

Answer 49

ATP/GTP

Question 50

Glutamate dehydrogenase is regulated by allosteric mechanisms. It is activated by

Answer 50

ADP/GDP

Question 51

Stimulation of glutamate dehydrogenase when energy levels are low increases the deamination of glutamate, to yield higher amounts of

Answer 51

α-ketoglutarate

Question 52

This reaction occurs primarily in the mitochondrion, and requires the cofactor

Answer 52

NAD

Question 53

NH3 that is released from glutamate is condensed with carbon dioxide (in the mitochondrion) to form

Answer 53

Citrulline

Question 54

Glutamate transfers NH3 (transamination) to -forms aspartate

Answer 54

Oxaloacetate

Question 55

Glutamate transfers NH3 (transamination) to oxaloacetate (forming aspartate), which donates the nitrogen to citrulline, yielding the

Answer 55

2nd nitrogen in urea

Question 56

This reaction occurs in the

Answer 56

Cytosol of liver cells

Question 57

In addition to α-ketoglutarate, there are other intermediates in the formation of urea that are linked to the TCA cycle. one example is

Answer 57

Oxaloacetate

Question 58

Transaminated to aspartate by aspartate aminotransferase

Answer 58

Oxaloacetate

Question 59

Arginino-succinate is cleaved to yield

Answer 59

Arginine and fumarate

Question 60

The conversion of arginine to ornithine requires the enzyme -expressed only in the liver

Answer 60

Arginase

Question 61

Transamination and oxidative deamination reactions are

Answer 61

Reversible

Question 62

The incorporation of ammonia into CO2 by carbamoyl phosphate synthase I requires

Answer 62

2 ATPs

Question 63

The conversion of aspartate to argininosuccinate requires

Answer 63

1 ATP

Question 64

The addition of NH3 to glutamate/aspartate by glutamine/asparagine synthase requires

Answer 64

1 ATP

Question 65

Digestive proteases are synthesized in the stomach, pancreas and intestine, but are active only in an

Answer 65

Extracellular location

Question 66

The α-NH3 groups are generated in all tissues, but are assimilated into urea only in the

Answer 66

Liver

Question 67

Only the liver expresses which three enzymes?

Answer 67

Arginase, glutaminase, and asparaginase

Question 68

The two nitrogen’s in urea are obtained from

Answer 68

Ammonia and aspartate

Question 69

Both nitrogens were originally present in

Answer 69

Glutamate

Question 70

The addition of nitrogen occurs in which two distinct intracellular regions of the liver cell?

Answer 70

Mitochondria and cytosol

Question 71

The carbon is obtained from CO2, which is transported as soluble

Answer 71

Bicarbonate

Question 72

Two key metabolites in the urea cycle are

Answer 72

Ornithine and citrulline

Question 73

Converts arginine to ornithine + urea, and is present only in the liver

Answer 73

Arginase

Question 74

What are the three key steps in nitrogen regulation?

Answer 74

Glutamine synthase, Alanine aminotransferase, and glutaminase

Question 75

When there is a sudden increase in the levels of amino acids, the cellular capacity to assimilate nitrogen into urea can become

Answer 75

Overwhelmed

Question 76

Since ammonia is highly toxic (due to CNS toxicity), a temporary mechanism functions to sequester excess nitrogen. I.e. NH3 is added to -serves as a temporary storehouse for excess nitrogen

Answer 76

Glutamate (generates glutamine)

Question 77

This process requires

Answer 77

ATP

Question 78

Urea is synthesized only in the liver, and several enzymes can release NH3 from compounds that are transported to this organ. What releaes NH3 from glutamine

Answer 78

Glutaminase

Question 79

Glutaminase specifically releases NH3 from glutamine, while oxidative deamination of glutamate also yields free

Answer 79

NH3 + α-ketoglutarate

Question 80

Glutaminase (unlike glutamate dehydrogenase), is only expressed in the

Answer 80

Liver

Question 81

Pyruvate that is released from alanine can be used for the synthesis of glucose, and returned to muscle (and other) tissues for energy production. This is termed the

Answer 81

Glucose-Alanine cycle

Question 82

Rapid increase in intracellular ammonia can be temporarily suppressed by the conversion of

Answer 82

Glutamate into glutamine

Question 83

Bacteria in the gut, and gastrointestinal bleeding can increase the blood levels of

Answer 83

Ammonia

Question 84

Activated to convert α-ketoglutarate to glutamate when ammonia levels rise rapidly

Answer 84

Glutamate dehydrogenase

Question 85

However, this results in a proportionate reduction in the level of a key TCA intermediate, which leads to reduced

Answer 85

Energy production

Question 86

Reduced function of the kidney can result in elevated levels of urea in the blood. An increased level of urea can then cross the intestinal cell wall and become cleaved by

Answer 86

Bacterial urease

Question 87

Bacterial urease releases

Answer 87

H2O and ammonia

Question 88

Ammonia can rapidly diffuse back into the blood and cause

Answer 88

Hyperammonemia

Question 89

The deamination of glutamine in the liver, by glutaminase, generates glutamate and NH3. NH3 is condensed with CO2 to form

Answer 89

Carbonoyl Phosphate

Question 90

NH3 is condensed with CO2 to form carbamoyl phosphate by carbamoyl phosphate synthase I in the

Answer 90

Mitochondrial matrix

Question 91

NH3 is condensed with CO2 to form carbamoyl phosphate by carbamoyl phosphate synthase I in the mitochondrial matrix. This represents the first assimilation of

Answer 91

Nitrogen into urea

Question 92

The addition of NH3 to oxaloacetate (via glutamate), provides a source for the -occurs in cytosol of liver cells

Answer 92

2nd nitrogen into urea

Question 93

The essential co-factor in all aminotransferases, and participates directly in the removal of alpha amino groups from amino acids

Answer 93

Pyridoxil Phosphate

Question 94

Derived from vitamin B6, and forms a Schiff base with an epsilon amino group in a lysine residue in the aminotransferases

Answer 94

Pyridoxil

Question 95

Pyridoxil is derived from vitamin B6, and forms a Schiff base with an epsilon amino group in a lysine residue in the

Answer 95

Aminotransferase

Question 96

However, when an aminotransferase binds an amino acid, the alpha-amino group in the amino acid forms a transient Schiff base with

Answer 96

Pyridoxal phosphate

Question 97

The key enzyme, and the rate-limiting step, in the Urea Cycle

Answer 97

Carbamoyl phosphate synthase I

Question 98

This rate-limiting step is positively regulated by

Answer 98

N-acetylglutamate

Question 99

The synthesis of N-acetylglutamate is stimulated by the presence of

Answer 99

Arginine

Question 100

The initial step in urea synthesis occurs in the mitochondria, and requires

Answer 100

2 ATP's per urea