Amino Acid Degradation

Question 1

In the fed state, what are amino acids primarily used for?

Answer 1

synthetic processes

Question 2

In the fasting state, what are amino acids primarily used for?

Answer 2

proteins are degraded so the amino acids can be used as fuel for energy, for gluconeogenesis and modified to maintain the levels of each amino acid.

Question 3

During the fasting state, what stimulates skeletal muscle to mobilize amino acids by breaking down proteins?

Answer 3

cortisol. Remember that skeletal muscle does not have glucagon receptors.

Question 4

What amino acids can be used to make propionyl CoA (which can be converted to succinyl CoA)

Answer 4

isoleucine (can also be converted to acetyl-CoA and enter the TCA that way), valine, and methionine

Question 5

Which amino acids can be used to make a-ketogluterate?

Answer 5

primarily glutamate

Question 6

What other AAs can make glutamate? (which can then be converted to a-ketogluterate to enter the TCA)

Answer 6

1) arginine and proline can make it through a glutamate-semialdehyde intermediate
2) histidine
3) glutamine (reversible)

Question 7

Which AAs can be used to make OAA?

Answer 7

aspartate and asparagine

NOTE: These two are used for the urea cycle and synthesis of purines

Question 8

How can phenylalanine, tyrosine, and leucine enter the TCA cycle?

Answer 8

1) phenylalanine can be converted to tyrosine
2) tyrosine and leucine can be converted to acetoacetate, which can then be converted to acetyl-CoA through acetoacetyl-CoA
3) tyrosine can also be converted directly to fumarate

Question 9

How can lysine and tryptophan enter the TCA cycle?

Answer 9

they can both be converted to a-ketoadipate, which can be converted to acetoacetyl-CoA, which can then be converted to acetyl-CoA

Question 10

What are the main carriers of nitrogen in the blood

Answer 10

alanine and glutamine

Question 11

What are the branched-chain amino acids?

Answer 11

Leu, Ile, Val; they are used for ENERGY in peripheral tissue- aka they are not going to be high in the blood

Question 12

Which of the following AAs will typically be in high concentration in the blood?

1) glutamine
2) valine
3) isoleucine
4) alanine
5) leucine

Answer 12

only glutamine and alpine; remember that they are the main nitrogen transporters in the body, whereas the other three are branched AAs which will not be found in the blood often but instead are used primarily for energy consumption in peripheral tissue

Question 13

T or F. All 20 amino acids can be broken down into pyruvate, acetyl-CoA or a citric acid cycle intermediate

Answer 13

T

Question 14

What happens to AAs before they are used for energy?

Answer 14

The a-amino group (nitrogen) is separated from its carbon skeleton before the amino acid is used to generate energy or converted to fatty acids for storage and discarded via the urea cycle

Question 15

What are the two ways to remove an amino group from an amino acid?

Answer 15

1. Transamination moves amino group between keto acids (In general, funnels amino groups into glutamate)
2. Deamination removes amino group as free ammonia.

Question 16

What enzyme family facilitates transamination?

Answer 16

aminotransferases or transaminases

Question 17

What cofactor is required for transamination reactions?

Answer 17

Pyridoxal phosphate (PLP) is a cofactor in transamination reactions.

NOTE: PLP is also a cofactor for some decarboxylation reactions

Question 18

What is PLP derived from?

Answer 18

PLP is derived from vitamin B6.

Question 19

T or F. Transamination reactions are readily reversible and are used in both amino acid synthesis and amino acid degradation.

Answer 19

T.

NOTE: Glutamic acid and a-ketogluturate are involved in many transamination reactions

Question 20

What AAs cannot perform transamination?

Answer 20

Lysine and Threonine

Question 21

Deamination of amino acids requires what?

Answer 21

input of water and NADP+. (generates an oxidized AA, NADPH, and a free ammonia group)

Question 22

Aminotransferases as diagnostic markers of liver disease or dysfunction

Answer 22

ALT = Alanine aminotransferase (old name -SGPT)
AST = Aspartate aminotransferase (old name -SGOT)

These enzymes are part of a standard serum panel

When ALT levels in the serum are above the standard range, it means that damage to the liver has released abnormal levels into the bloodstream. (ALT is predominantly in liver but low levels are elsewhere)

When AST levels in the serum are above the standard range, it means that damage to the liver or cardiac or skeletal muscle has released abnormal levels into the bloodstream.
AST is high in liver, cardiac muscle and skeletal muscle

Question 23

How do the branched-chain AAs enter the TCA cycle?

Answer 23

ALL three are trans-aminated to a-keto acids initially, and then:

Isoleucine- can become succinyl CoA (though propionyl CoA intermediate) OR acetyl CoA (both through addition of NAD+ and FAD+)

Leucine- can be become HMG-CoA through addition of NAD+ and FAD+, which can then become acetyl CoA (either directly or through acetoacetate) to enter the TCA

Valine- can become succinyl CoA through addition of NAD+ and FAD+ (though propionyl CoA intermediate)

The reduced NADH and FADH2 that are generated from these reactions are used for energy generation

Question 24

In high energy states, what can a-keotgluterate be converted to?

Answer 24

glutamate (which can be converted to glutamine for nitrogen transport)

Question 25

What is Maple syrup urine disease (MSUD) (aka Branched-chain ketoaciduria) caused by?

Consequences? Clinical Manifestation?

Answer 25

caused by a deficiency of the Branched-chain a-keto acid dehydrogenase complex responsible for converting the a-keto intermediates of the branched-chain AAs (isoleucine, leucine, and valine) during their integration into the TCA in fasting states.

Since the branched AAs are not being broken down, they are high level in the blood and compete for transporters in the blood brain barrier, leading to neurologic symptoms

Name comes from sweet odor of urine, similar to maple syrup

Question 26

What is the mode of inheritance of MSUD?

Answer 26

autosomal recessive (~1:180,000)

Question 27

What five AAs can yield alanine when degraded?

Answer 27

Cysteine, Glycine, Serine and Threonine (all via Pyruvate) and Tryptophan directly

Alanine itself is also a source of Alanine

Question 28

What four AAs can yield glutamine when degraded?

Answer 28

Arginine, Proline and Histidine (via Glutumate) and Glutamate directly

Glutamine itself is also a source of Glutamine

Question 29

What is methionine used for?

Answer 29

Used for synthesis of Cysteine, SAM

Question 30

What are Tyrosine and Phenylalanine

used for?

Answer 30

Used for synthesis of melanin (pigment), dopamine and epineprhrine (catacholamine), tyroxine (hormones)

Question 31

What is the fate of alanine deposited from skeletal muscle into the bloodstream?

Answer 31

transported from Muscle to Liver, converted to Pyruvate and used for Gluconeogenesis (Glucose-Alanine Cycle).

during the conversion of alanine to pyruvate (and subsequently glucose) in this cycle, ammonia/urea is given off as a byproduct

Question 32

What are the steps of the Glucose-Alanine cycle?

Answer 32

in muscle, glucose is broken down to pyruvate, which can then form alanine (with addition of NH3 from branched-chain AAs). Alanine enters the bloodstream and goes to the liver where it re-forms pyruvate (and gives off NH3), which is then converted to glucose via gluconeogenesis. Circulating glucose can go to many peripheral tissues

Question 33

What are glucogenic AAs?

Answer 33

Amino acids carbon skeletons that form pyruvate or a citric acid cycle intermediate and can be used in gluconeogenesis

Question 34

What are ketogenic AAs?

Answer 34

Amino acids carbon skeletons that form acetyl-CoA and can be used to form fatty acids or ketone bodies

Question 35

What AAs are ketogenic only?

Answer 35

Leucine and Lysine

Question 36

What AAs are Ketogenic AND Glucogenic?

Answer 36

Isoleucine, Threonine, Phenylalanine, Tryrosine, and Tryptophan (last three are aromatic side-chains)

all 13 others are glycogenic only

Question 37

What is the fate of glutamine in the bloodstream?

Answer 37

glutamine is formed from glutamate (which is formed from a-keotgluterate and other AAs) through the addition of ATP and NADPH and enters the bloodstream to travel to the liver or the kidney where it is deaminated and reconverted to a-ketogluterate for energy use (or other things).

Glutamine is the major carrier of nitrogen in the blood and can be transported via blood from skeletal muscle and peripheral tissue to the liver where the nitrogen enters the Urea Cycle, and a-ketoglutarate used for energy or other processes

Glutamine can be transported via blood from skeletal muscle and peripheral tissue to the kidney where the nitrogen is eliminated as ammonium which maintains pH in urine, and a-ketoglutarate used for energy or other

Question 38

What are the fates of a-ketogluterate in the kidney?

Answer 38

1) TCA cycle
2) convert to glucose
3) convert to serine or alanine