Amino Acid Nitrogen And Urea Cycle

Question 1

Amino acid functions

Answer 1

. Protein synthesis

. Precursors for synthesis of specialized N-containing compounds

Question 2

T/F there is long-term amino acid storage in body

Answer 2

F

Question 3

Sources of amino acids

Answer 3

. Synthesis of nonessential amino acids
. Digestion and absorption of dietary protein
. Degradation (turnover) of body proteins

Question 4

T/F most adults are in net nitrogen balance (N in = N out)

Answer 4

T

Question 5

How do amino acids enter body pool?

Answer 5

. Cellular synthesis of nonessential amino acids
. Directions and absorption of dietary amino acids
. Degradation of body proteins

Question 6

How are nonessential amino acids synthesized?

Answer 6

. Metabolism intermediates formed during glycolysis and TCA cycle

Question 7

Essential amino acids

Answer 7

. Phe
. Val
. Thr
. Trip
. Ile
. Met
. His
. Arg
. Leu
. Lys

Question 8

Nonessential amino acids

Answer 8

. Ser
. Gly
. Cys
. Ala
. Asp
. Asn
. Glu
. Gln
. Pro
. Tyr

Question 9

Synthesis of Tyr from Phe

Answer 9

. Hydroxylation of Phe from diet via phenylalanine hydroxylase (PAH)
. Dependent on tetrahydrobiopterin (BH4)
. Rxn first step in catabolism of phe that forms fumarate and acetoacetate

Question 10

What metabolic intermediate makes Ser

Answer 10

3-phosphoglycerate from glycolysis

. Gly and Cys made from Ser

Question 11

What metabolic intermediate can form Ala

Answer 11

Pyruvate

Question 12

What metabolic intermediate can form Aspartate?

Answer 12

Oxaloacetate

. Aspartate then can form asparagine

Question 13

Aminotransferase enzymes

Answer 13

. Catalyze trans am inaction of alpha-Ketoacid intermediates to form Ala, Glu, and Asp
. Depends on vit. B6 (pyridoxal phosphate) for transfer of amino group

Question 14

Amidation fo Aspartate

Answer 14

. Glutamine is nitrogen donor
. Done via Asparagine synthetase
. Needs ATP
. Forms asparagine

Question 15

Amidation of glutamate

Answer 15

.done via glutamine synthetase
. Needs ATP
. Forms glutamine
. Ammonia is nitrogen donor

Question 16

Synthesis of Pro and Arg from Glu

Answer 16

. Deamidation of Gln to Glu via glutaminase
. Glu then turns into Pro and Ornithine
. Ornithine turns into citrulline which then undergoes steps to form Arg

Question 17

Synthesis of Ser, Gly, and Cys from 3-phosphoglycerate

Answer 17

. 3-PG turns into Ser
. Ser dependent on THF and Vit. B6 forms Gly
. Ser dependent on Vit. B6 and homocysteine form cystathionine that forms Cys dependent on vit. B6 again

Question 18

Mechanism for transport of toxins ammonia w/in body

Answer 18

. Glu Gln conversation by glutamine synthetase/glutaminase

Question 19

Formation of homocysteine

Answer 19

. Formed during catabolism of Met

Question 20

Absorption of dietary protein in stomach

Answer 20

. HCL denatures proteins
. Pepsinogen is secreted, undergoes conformational change from low pH autoactivation via limited proteolytic to form active pepsin
. Pepsin further activates other pepsinogen
. Initiates breakdown of dietary protein to shorter polypeptides

Question 21

Digestion of dietary protein in small intestine

Answer 21

. Pancreatic enzymes activated via limited proteolysis initiated by enteropeptidase
. Each activated enzyme hydrolyzes specific peptide bonds of chains making oligopeptides
. Oligopeptides degraded to free amino acids via aminopeptidases in brush border

Question 22

Enteropeptidase

Answer 22

. Extracellular enzyme on luminal surface of intestinal epithelial cells
. Activates trypsinogen to trypsin
. Trypsin activates more trypsinogen and other zymogens

Question 23

Trypsin action

Answer 23

. Hydrolyzes internal peptide bonds where carboxylase group is provided by Arg or Lys

Question 24

Absorption of amino acids from small intestine

Answer 24

. Free amino acids and some di and tri-peptides absorbed
. Specific transporters on intestinal epithelial cell surface
. Di and tri-peptides absorbed and then hydrolyzed to free amino acids w/in cell
. Only free amino acids released into portal circulation

Question 25

Lab evaluation of exocrine pancreatic function

Answer 25

. Pancreatic elastase measured through fecal elastase | . Presence of this means exocrine dysfunction

Question 26

Degradation of body proteins

Answer 26

. Daily turnover of 300-400g protein . Degraded via proteases in lysosome (ATP-independent) or via ubiquitin-proteasome system in cytosol (ATP-dependent) . Amino acids enter body pool for utilization

Question 27

Removal of amino acid N from Glu

Answer 27

. Glu undergoes oxidative deamination to make Ketoglutarate and ammonia . Done via glutamate dehydrogenase (GDH) . Needs NADPH . Reaction can go both ways

Question 28

Other than Glu, what are other sources of ammonia

Answer 28

. Bacterial breakdown of urea in intestine

Question 29

Role of Ala and Glu in transporting amino acid N to liver

Answer 29

. N removed during aminoa acid catabolism in peripheral tissues is brought to liver for detoxification . Ala and Glu transport N from skeletal muscle

Question 30

What is major extrahepatic site for amino acid catabolism?

Answer 30

Skeletal muscle

Question 31

Besides transporting N, what else does Ala deliver to liver?

Answer 31

Carbon atoms for hepatic gluconeogenesis

Question 32

Detoxification of amino acid N in liver

Answer 32

. Done via urea cycle or Glu synthesis in perivenous hepatocytes

Question 33

Percentage of N detoxified through urea synthesis?

Answer 33

90%

Question 34

Number of reactions in urea cycle

Answer 34

5

Question 35

Urea cycle

Answer 35

. Low-affinity high capacity mechanism . Found in periportal hepatocytes . N from ammonia or Asp and carbon from bicarbonate are incorporated into urea . ATP-dependent . Irreversible . Complete cycle only completed in liver (some reactions w/in cycle can be done in other tissues) . Net rxn: NH4 + Asp + 3ATP + H2O -> Urea + Fumarate = 2ADP + AMP + 2Pi + 2 PPi . Overall NH4 + Asp + 3ATP -> urea

Question 36

Where is glutamine transported to release ammonia?

Answer 36

From liver to kidney

Question 37

PH regulation w/ urea cycle during acidosis

Answer 37

. Drop in pH inhibits periportal urea synthesis via dec. transport of Glu into hepatocytes and inhibition of glutaminase . Inc. in perivenous synthesis of Glu to prevent hyperammonemia . Inhibition of urea cycle preserve bicarbonate

Question 38

PH regulation during alkalosis by urea cycle

Answer 38

. Urea synthesis inc. and Glu synthesis dec. causing inc. consumption of bicarbonate