Biochem Exam 5: Aa Metabolism 2 (Urea Cycle)

Front 1

Where does the C and N come from to produce urea?

Back 1

One N from aspartate, one from NH4, and C from CO2.

Front 2

Obj
In what 3 ways is N removed from AAs? What AAs are usually involved?

Back 2

Deamination (glutamate via glutamate dehydrogenase using NADH).
Deamidation (glutamine and aspargine via glutaminase).
Transaminases (transfer from alpha AA to glutamate).

Front 3

Obj.
What enzyme, coenzyme, and vitamin is required for transamination?

Back 3

enzyme- transaminase (aminotransferase)
coenzyme- pyridoxal phosphate (PLP)
vitamin- B6 - pyridoxine

*gets nitrogen from glutamate

Front 4

What is the main way ammonia is detox. in the brain?

Back 4

Glutamate + NH4 via glutamine synthetase using ATP resulting in glutamine

Front 5

Obj.
What are the 3 fxns of glutamate in the urea cycle?

Back 5

1. Picks up nitrogen from other AAs via transaminase rxns
2. Can donate nitrogen (NH4+) via glutamate dehydrogenase, deamination rxn
3. Can transaminate OAA to aspartate which can then provide amino group to urea

Front 6

Obj
Where does urea synthesis take place (tissue & intracellularly?

Back 6

Liver ONLY! (alanine and glutamine carry the N to the liver from other cells)

begins in mitochondria (steps 1 & 2) & ends in cytosol (steps 3-5)

Front 7

Obj.
What steps of urea cycle use ATP?

Back 7

step 1 (2)
step 3 (1)

Front 8

What is the rate limiting step in the urea cycle? How is it allosterically regulated?

Back 8

step 1 via CPSI.
N-Acetyl-glutamate is a positive regulator.

Front 9

When is N-acetyl-glutamate formed?

Back 9

High levels of arginine.

Front 10

Obj
What links the TCA to the urea cycle?

Back 10

Fumurate from urea cycle can be fed into TCA to yield energy. OAA can form aspartate through transamination and can be fed into urea cycle.

Front 11

What is the difference btw. urea synthesis during short term and long term fasting?

Back 11

Short term: Muscle breakdown. AAs transport to liver for gluconeo. and urea excretion thus increases. L/T: Ketone body synthesis is primary energy from FAs so urea excretion decreases.

Front 12

What causes Type I hyperammonemia?

Back 12

Def in CPS-1 or N-acetylglutamate synthase

Front 13

What causes Type II hyperammonemia?

Back 13

Def in ornithine transcarbamoylase. X-linked recessive.

Front 14

Will urine orotate be low/normal/high in Type II hyperammonemia? Why?

Back 14

HIGH. Shifts CP to alt. pathway when OTC is shut-down.

Front 15

obj.
list major forms of nitrogen excretion in the urine

Back 15

urea (urea cycle) *90% of excreted nitrogen
NH4+ (glutamine (kidney))
creatinine (creatine phosphate)
uric acide (purines)

Front 16

obj.
major sources of ammonia in the human body

Back 16

*main source is degradation, transamination
-also through deamination

Front 17

obj.
what is the central role of alanine & glutamine in nitrogen removal in human body?

Back 17

alanine- removes nitrogen through urea cycle via liver transport

glutamine- important in kidney, removes ammonia to urine

Front 18

How is NH4+ (ammonia) cleared?

Back 18

urea cycle

*ammonia is toxic

Front 19

How is the carbon backbone from AA degradation used during the fed and fasting state?

Back 19

fed- synthesis of glycogen & TGs
fasting- energy production

Front 20

What do the following blood metabolites indicate:
Blood Urea Nitrogen (BUN)
Creatinine
BUN/Creatinine ratio
Uric Acid
Ammonia

Back 20

Blood Urea Nitrogen (BUN): increases w/ kidney damage, decreases w/ liver damage or pregnancy
Creatinine: increases w/ kidney damage
BUN/Creatinine ratio: increases w/ dehydration
Uric Acid: increases w/ gout
Ammonia: increase in Urea cycle disorders or liver damage

Front 21

________ and _________ are present at high levels in liver.

High levels in plasma indicates what?

Which one can be used to diagnose MI?

Back 21

Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST)

indicates liver damage

AST, although ALT is more specific

Front 22

Ammonia from AA degradation is toxic and its concentration must be controlled using 2 major mechanisms:

Back 22

1. transamination reactions collect nitrogen on glutamate
2. 3 enzymes fix free ammonia into organic molecules

Front 23

What 3 enzymes are used to "fix" free ammonia?

Back 23

1. glutamate dehydrogenase (requires NADH/NADPH)
alpha-ketoglutarate + NH4+ --> glutamate

2. glutamine synthetase (requires 1 ATP)
glutamate + NH4+ --> glutamine

3. carbamoyl phosphate synthetase I (CPSI, requires 2 ATP)
CO2 + NH4+ --> carbamoyl phosphate

Front 24

2 main purposes of alanine transport to liver:

3 main sources of alanine:

how is glutamine converted to alanine?

Back 24

purposes:
1. removes nitrogen through urea cycke
2. gluconeogenesis

sources:
1. muscle
2. kidney
2. intestine

glutamine --(glutaminase)--> glutamate--(ALT)--> alanine

Front 25

Glutamine is produced mostly by:


Glutamine is used mostly by:

Back 25

produced: muscle & brain


used: kidney, gut, immune cells, & liver

Front 26

Step 1 of Urea cycle:
location
enzyme
reaction
regulation

Back 26

location- mitochondria
enzyme- CPSI (carbamoyl phosphate synthase 1)
reaction- ammonia + bicarbonate-->carbamoyl phosphate
regulation- requires 2 ATP, activated by N-acetyl-glutamate (which is activated by high arginine levels)

Front 27

Step 2 of Urea cycle:
location
enzyme
reaction
regulation

Back 27

location- mitochondria
enzyme- ornithine transcarbamoylase
reaction- ornithine + carbamoyl phosphate--> citrulline
regulation

Front 28

Step 3 of Urea cycle:
location
enzyme
reaction
regulation

Back 28

location- cytosol
enzyme- argininosuccinate synthetase
reaction- citrulline-->argininosuccinate
regulation- requires 1 ATP

Front 29

Step 4 of Urea cycle:
location
enzyme
reaction
regulation

Back 29

location- cytosol
enzyme- argininosuccinate lyase
reaction- argininosuccinate-->arginine + fumarate
regulation- none

Front 30

Step 5 of Urea cycle:
location
enzyme
reaction
regulation

Back 30

location- cytosol
enzyme- argase
reaction- arginine-->urea + ornithine
regulation- n/a

Front 31

How is ornithine transported into the mitochondria from the cytosol?

What does a def in this enzyme cause?

Back 31

ornithine translocase


def causes hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome

Front 32

A deficiency in what enzyme causes Citrullinuria type 1?

Back 32

argininosuccinate synthetase

Front 33

A deficiency in what enzyme causes argininosuccinyl acidemia?

Back 33

argininosuccinate lyase

*only way arginine is produced in human body

Front 34

Deficiency in what enzyme causes argininemia?

What are some other uses for arginine?

Back 34

arginase

protein synthesis & nitric oxide synthesis

Front 35

In general, the urea cycle is regulated via:

Back 35

-increased by high protein diet & excessive degradation of body proteins
- by concentration of substrates & intermediates

Front 36

Deficient urea cycle leads to hyperammonemia. What are the symptoms, due to high toxicity of ammonia in NS?

Back 36

ecephalopathy, cerebral edema, seizures, nausea, vomiting, lethargy, coma, and death

Front 37

Differentiate btwn primary & secondary hyperammonemias

Back 37

primary- caused by deficient/defective urea cycle enzymes

secondary- may be caused by hepatic failure or genetic defects

Front 38

In order to diagnose a specific enzyme deficiency, blood/urine metabolites may be checked. Metabolites that occur (before/after) the deficiency in the cycle, should be accumulated

Back 38

before

metabolites after deficiency will be missing

Front 39

What are the 2 main ways to treat urea cycle disorders?

Back 39

1. reduce ammonia load in urea cycle
-low protein diet, avoid fasting
-scavenger drugs

2. provide urea cycle intermediates (intravenous)
-arginine
-citrulline

Front 40

How do the following scavenger drugs decrease AA load in urea cycle?
Benzoate
Phenylbutyrate

Back 40

Benzoate- conjugates Glycine--> hippuric acid

Phenylbutyrate- conjugates Glutamin--> phenylacetylglutamine

*for excretion