Amino Acid Metabolism, Transaminases, Urea Cycle

Question 1

What happens to the amine groups from AA?

Answer 1

Removed and packed into urea

Question 2

Where is urea formed?

Answer 2

In the liver

Question 3

What is major form of getting rid of nitrogen?

Answer 3

Through urea

Question 4

Even though NH4+ is toxic to us, why is it still a nitrogenous excretory products?

Answer 4

because it is made in the kidney and is excreted right there. It doesnt have to travel through the blood

Question 5

How are proteolytic enzymes first produced?

Answer 5

as zymogens (inactive enzyme precursors)

Question 6

Why are proteolytic enzymes inactive when first generated?

Answer 6

They would break down the proteins in our cells

Question 7

What is the earliest point in the GI tract that protein digestion can begin?

Answer 7

In the stomach with HCL - hydrolysis of peptide bonds

Question 8

Where do most protein digestion occurs?

Answer 8

In the small intestine with the help of activated zymogens

Question 9

Where does the trypsin protease cleaves?

What kind of protease is it?

Answer 9

at AA with positive charges (Arg, Lys)

Endo protease

Question 10

Where does the pepsin protease cleaves?

What kind of protease is it?

Answer 10

Phe, Tyr, Glu, Asp

Endo protease

Question 11

Where does the amino peptidases cleave?

What kind of protease is it?

Answer 11

At the amino terminus (N terminus)

Exo protease

Question 12

Where does the carboxy protease cleave?

What kind of protease is it?

Answer 12

At the carboxy terminus (C - terminus)

Exo protease

Question 13

How do AA enter cells?

Answer 13

Via Na-coupled transporters

Question 14

How do Na-AA coupled transporters work?

Do they require energy?

Answer 14

They work via the Na+ gradient
There is more Na+ outside the cell so it travels into the cell and carries along AAs
It doesn’t require energy/ATP

Question 15

How does peptide absorption work?

Does it require energy?

Answer 15

Peptides are carried from the lumen of the small intestine to the enterocyte via peptide carriers in the brush border membrane
Energy is required
Peptides are metabolized into free AA in the enterocyte
Only free AA are absorbed into the blood

Question 16

What is kwashiorkor disease

Answer 16

Protein deficiency in the diet

symptoms: swollen belly, delayed growth, frequent infections

Question 17

What is Hartnup disease?

Answer 17

hereditary defect in transport of nonpolar AA (especially Trp)
Symptoms: dermatitis, failure to thrive, photosensitivity, intermittent ataxia, nystagmus, tremor

Question 18

In the following peptide: Met - Cys - Pro - Met - Leu - Glu -/- Gln - Pro - Leu
The “/” represents a cleavage site for which enzyme?
A. Trypsin
B. Pepsin
C. Carboxypeptidase A
D. Aminopeptidase

Answer 18

B.

AA on the amino terminus end is the important one ie Glu. Since Glu is negative then it is recognized by pepsin

Question 19

What are 3 pathways that produce ammonia?

Answer 19

1. Deamination of AAs
2. Purine nucleotide cycle
3. Bacteria in the gut

Question 20

Which system is very sensitive to high ammonia levels?

Answer 20

CNS

Question 21

Where is nitrogen transported from and in what form?

Where is it transported to?

Answer 21

From peripheral tissues
as amino acid
Liver

Question 22

How is Nitrogen excreted?

Answer 22

as urea

Question 23

What enzymes or pathways are involved in the processing of nitrogen?

Answer 23

transaminases
glutamate dehydrogenases
glutamine synthases
glutaminase
urea cycle (critical)

Question 24

What is transamination?

Answer 24

Transfer of amino group to an a-keto acceptor

Question 25

Which AAs do not undergo transamination

Answer 25

Lysine and threonine

Question 26

What is the cofactor needed in transamination?

Answer 26

pyridoxal phosphate (pyridoxine, vit B6)

Question 27

What are two enzymes involved in transamination and where are they?

Answer 27

``` Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) high in the liver ```

Question 28

Why does increases ALT and AST in the blood indicate liver damage?

Answer 28

Because these enzymes are in the liver. If they're found in the blood then some damaged happened to the liver and they leaked out

Question 29

Is transamination reversible

Answer 29

highly reversible

Question 30

Where does glutamate dehydrogenase reaction occurs?

Answer 30

Mitochondria of most cells

Question 31

Is glutamate dehydrogenase reaction reversible?

Answer 31

yes

Question 32

What is the main purpose of glutamate dehydrogenase?

Answer 32

major source of free ammonia for the urea cycle

Question 33

What is another source of N for the urea cycle?

Answer 33

Aspartate

Question 34

How is N transported to the liver via glutamine?

Answer 34

- Glutamine is produced in skeletal muscle from glutamate - It is converted back to glutamate in the liver and NH3 is produced - GluDH releases NH3 from Glu, leaving a-KG

Question 35

How is N transported to the liver via alanine?

Answer 35

Alanine is produced in skeletal muscle from pyruvate - it is converted back to pyruvate in the liver, NH3 produced - NH3 goes to urea cycle, pyruvate goes to gluconeogenesis etc

Question 36

What are the important AAs for the urea cycle?

Answer 36

1. Glutamate - directly gives N group 2. Glutamine/Aspartate 3, Alanine

Question 37

What is the importance of the urea cycle?

Answer 37

Produces urea .Major means of detoxifying/disposing of ammonia

Question 38

Where does the urea cycle occurs?

Answer 38

Liver (mitochondria/cytosol)

Question 39

What are the reactions of the urea cycle?

Answer 39

1. Synthesis of carbamoyl phosphate 2. Formation of citrulline 3. Formation of arginosuccinate 4. Formation of arginine 5. Formation of urea and ornithine

Question 40

Where does the first N comes from in the urea cycle? | Where does the second N comes from?

Answer 40

Free ammonia | Asp in the cytosol

Question 41

What is the rate limiting step in the urea cycle

Answer 41

NH4+ + HCO3- --> carbamoyl phosphate | catalyzed by CPSI

Question 42

How is the urea cycle regulated?

Answer 42

1. Substrate availability (ammonia and other substrates) 2. allosteric activation of CPSI by N-acetylglutamate 3. induction/repression of the synthesis of urea cycle enzymes

Question 43

How does N-acetylglutamate regulated by CPSI

Answer 43

It is an allosteric activator

Question 44

Which state, Fed or fasting, is urea highest?

Answer 44

fasting

Question 45

A poisoning victim with severe liver damage might present with elevated blood levels of which of the following metabolites? A. Carbamoyl phosphate B. Ammonium C. Urea D. ATP

Answer 45

B

Question 46

Elevated blood urea nitrogen (BUN) levels

Answer 46

kidney disease b/c high protein leads to increased AA metabolism, excess N produces elevated urea in blood In kidney failure, kidneys are unable to remove urea from blood

Question 47

Decreased BUN levels

Answer 47

low protein diet malnutrition liver failure B/c low protein/malnutrition leads to overall decreased AA metabolism, less N produces low urea in the blood In the liver, decreased urea cycle, liver does not package NH3 into urea

Question 48

Urea cycle disorders

Answer 48

hyperammonemia (elevated NH4 in blood) | symptoms include lethargy, slurred speech, seizures, coma

Question 49

Effects of high concentration of ammonia

Answer 49

would drive glutamine synthase glutamate + ATP + NH3 --> glutamine + ADP + Pi This would deplete glutamate - a neurotransmitter and precursor for synthesis of the neurotransmitter GABA

Question 50

What would affect glutamate dehydrogenase reaction to reverse?

Answer 50

depletion of glutamate and high ammonia level glutamate + NAD (P)

Question 51

What is the result of depleting a-ketoglutarate

Answer 51

impair energy metabolism in the brain