Week 3 Amino Acid Catabolism

Question 1

before an amino acid can be utilized for energy producition what must it be stripped of?

Answer 1

nitrogen content

Question 2

The first step of AA catbolism is what?

Answer 2

transfer of the amino group (transamination) to alpha-ketogluterate to form Glutamate

Question 3

what enzyme class facilitates the amino group transfer?

Answer 3

transaminases or aminotransferases

Question 4

after Glu is made via transamination, what is its fate (2)

Answer 4

recycled to support new amino acid synthesis

deaminated and ammonium is formed

Question 5

why is the released ammonia bad?

Answer 5

ammonia is a neurotoxin (can cross blood-brain barrier)

Question 6

what is hyperammonemia

Answer 6

abnormal elevation of blood ammonia levels (can cause coma or death)

Question 7

what is our bodies solution to limiting ammonia in our bodies?

Answer 7

ammonia is converted to non-toxic metabolites

Question 8

how is ammonia “carried” in peripheral tissue?

Answer 8

ammonia is wither incorporated into precursor molecules to form glutamine or alanine

Question 9

what enzyme is present in the liver and kidneys that converts glutamine (a carrier of ammonia) back to glutamate and ammonia?

Answer 9

glutaminase

Question 10

where is the ultimate site of ammonia detoxification?

Answer 10

the liver

Question 11

what is the detoxified form that ammonia is converted to in the liver? what is this biochemical pathway callled

Answer 11

urea. urea cycle

Question 12

why is urea a good product for excretion?

Answer 12

no net charge, highly water soluble (very polar)

Question 13

if there is little free AA, what happens to the urea cycle? why?

Answer 13

urea cycle decreases. AA allosterically regulate the urea cycle such that if there is not sufficient free AA, the cycle (and related protein degradation) does not occur

Question 14

how much ATP is consumed for every molecule of Ammonia in the urea cycle?

Answer 14

3 ATP/ammonia

Question 15

what is the strucutre of urea. where do the atoms come from?

Answer 15

NH2NH2CO (Carbon from CO2, N from ammonia, N from Asp)

Question 16

other than urea, what is produced during urea cycle?

Answer 16

fumerate, this can be used for intermediary metabolism (including gluconeogenesis)

Question 17

what is uremia?

Answer 17

an increase in Blood Urea Nitrogen (BUN) correlated with renal failure

Question 18

what organ is responsible for excretion of urea from the blood?

Answer 18

kidneys

Question 19

what causes hyperammonemia?

Answer 19

defect in liver fxn leading to failure to detoxify ammonia. can be congenital or acquired

Question 20

what are some symptoms of hyperammonemia?

Answer 20

ammonia crosses blood-brain barrier and results in tremors, slurred speech, vomiting, coma, death

Question 21

what is a congenital defect?

Answer 21

a defect present from birth

Question 22

what is a potential cause of congenital hyperamonemia?

Answer 22

a genetic defect in any of the FIVE urea cycle enzymes

Question 23

how many enzymes are used in the urea cycle

Answer 23

5

Question 24

Symptoms of Congenital Urea Cycle Disorders (UCDs) tend to be more severe when which enzymes are affected? when do symptoms arise?
why?

Answer 24

more severe when enzymes earlier in the urea cycle are impacted (CPSI), symptoms arise 24 to 48 hours after birth, urea cycle is not needed in utero

Question 25

how would you treat hyperammonemia? 2

Answer 25

restrict protein and supplement essential AA

create an alternative pathway for ammonia excretion

Question 26

what is the alternate pathway for ammonium excretion?

Answer 26

oral Na benzoate or Na phenylbutyrate can complex with Gly or Glu (respecitvely) to form readily excretable water soluble adducts

Question 27

how can hyperammonemia be acquired?

Answer 27

liver damage: alcohol abuse, hepatitis, fatty liver disease

Question 28

what is hepatic encaphalopathy?

Answer 28

a condition caused by acquired hyperammonemia. neurolopsychiatric alterations and coma. seen in half of liver damage cases.

Question 29

what is urease?

Answer 29

a protein produced by certain bacteria that converts urea to ammonia. this is problematic because it can result in kidney stones due to UTI

Question 30

carbon skeletons of degraded AA (AA-Amino group) are classified as what?

Answer 30

ketogenic or glucogenic

Question 31

what can glucogenic AA feed into?

Answer 31

feed into TCA, gluconeogenesis, non-essential AA synthesis

Question 32

what can ketogenic AA feed into?

Answer 32

form Ac-CoA which can only feed into TCA, FA or ketone body synthesis (starvation)

Question 33

every acetyl-CoA that feeds into the TCA cycle produces how much ATP

Answer 33

12 (this compensates for the 3 ATP needed to produce urea in urea cycle

Question 34

Most non-essential AA are…why might this be?

Answer 34

glucogenic. probably an evoluiton advantage becuase all these AA can be readily enter intermidiary metabolis in a single step

Question 35

what are the 6 wholly or partly ketogenic AA?

Answer 35

Leu, Lys (wholly)

Ile, Phe, Trp, Tyr

Question 36

the ketogenic AA typically are broken down to…

Answer 36

Acetyl-CoA (cant be converted to pyruvated, enters TCA)

Question 37

what are some metabolites that glucogenic AA are converted to?

Answer 37

pyruvate, oxaloacetate (NOT Acetyl-CoA)