Protein Metabolism I (Lecture 3 - Exam 3)

Question 1

AAs are the source of XXXXXX consumed in the diet. What is it used for?

Answer 1

NITROGEN

Used for protein synthesis and synthesis of nitrogen containing non-protein compounds

Question 2

How are AAs classified?

Answer 2

Several ways:

Essential & Non-essential (and conditional), or

Glucogenic & Ketogenic

Question 3

Explain catabolism of AAs.

Answer 3

(1) Removal of the N. group, which will be excreted from the body. It will be converted to ammonia, then urea. It will be excreted through the urine.

(2) The carbon skeletons from those AAs can be utilized in several ways, including:
—Immediate energy source (via Kreb’s Cycle)
—Some can be converted to glucose, which can go through glycolysis
—Some can be converted to ketone bodies
—Excessive AA intake can also result in the biosynthesis of FAs and cholesterol

Question 4

Glucogenic AAs

Answer 4

Catabolism yields pyruvate or an intermediate of the Krebs Cycle

Question 5

Ketogenic AAs

Answer 5

ONLY LEUCINE & LYSINE (which are also essential)

Catabolism yields acetoacetate, acetyl CoA, acetoacetyl CoA

Question 6

Is alanine glucogenic or ketogenic?

Answer 6

GLUCOGENIC

Question 7

Is asparagine glucogenic or ketogenic?

Answer 7

GLUCOGENIC

Question 8

Explain the catabolism of asparagine.

Answer 8

ASPARAGINE is a non-essential AA. This is an example of a transamination reaction.

ASPARAGINE ———–> ASPARTATE ————> OAA
Asparaginase Aminotransferase (PLP/B6 dependent)

Question 9

Asparaginase

Answer 9

Enzyme that converts ASPARAGINE to ASPARTATE by removing the NH3 (Nitrogen) group from asparagine

Question 10

Aminotransferase

Answer 10

Enzyme that converts ASPARTATE to OAA, requires PLP/B6.

Question 11

Explain the role of alpha-ketoglutarate in asparagine catabolism.

Answer 11

We are going to have alpha-ketoglutarate from the Kreb’s Cycle, which will pick up that other NH3 group and be converted to GLUTAMATE.

Question 12

What is another example of a transamination reaction?

Answer 12

Alanine is a non-essential AA

ALANINE <————-> PYRUVATE
Alanine aminotransferase (PLP/B6)

Again, here alpha-ketoglutarate will pick-up the NH3 group and will be converted to GLUTAMATE.

Question 13

How are AAs catabolized?

Answer 13

AA degradation involves removal of the alpha-amino group, followed by catabolism of the resulting alpha-keto acids (carbon skeletons). These pathways converge to form 7 intermediate products (OAA, pyruvate, alpha-ketoglutarate, fumarate, succinyl CoA, acetyl CoA, acetoacetate).

Question 14

What are the 4 potential products of the carbon skeleton from AA catabolism?

Answer 14

(1) Immediate energy source (via Kreb’s Cycle)

(2) Some can be converted to Glucose (which will go through glycolysis)

(3) Some can be converted to Ketone bodies

(4) Excessive FA intake can result in FA/Cholesterol biosynthesis

Question 15

BCAAs

Answer 15

LEUCINE, ISOLEUCINE, VALINE

–The only essential AAs that undergo transamination

–Amino group has branch chain

–Primarily catabolized in the muscle versus the liver

Question 16

Where are BCAAs mainly catabolized?

Answer 16

MUSCLE

Question 17

Explain BCAA catabolism.

Answer 17

(1) Amino group is transferred to alpha-ketoglutarate by BRANCHED CHAIN AMINO ACID TRANSFERASE, expressed primarily in muscle.

(2) Oxidative Carboxylation: Carboxyl group is removed by BCKD complex, NADH is formed.

(3) DEHYDROGENASE enzyme, FADH is formed.

(4) End products of catabolism yield: acetyl CoA, succinyl CoA, acetoacetate, glutamine, and alanine. AKA we end up with a number of glucogenic and ketogenic intermediates that can go into gluconeogenesis or ketone formation, depending on the physiological state of the body.

Question 18

BCKD complex

Answer 18

BRANCHED CHAIN ALPHA KETO ACID DEHYDROGENASE complex

Question 19

What are the end products of BCAA catabolism?

Answer 19

ACETYL COA

SUCCINYL COA

ACETOACETATE

GLUTAMINE

ALANINE

Question 20

Maple Syrup Urine Disease

Answer 20

Autosomal recessive disorder resulting in partial or complete loss of BCKD

This results in BCAA and/or alpha-keto acid derivatives to accumulate in the blood (which is toxic).

It can result in neurological and mental disorders if not treated.

It requires early identification to avoid long-term issues

It requires life-long dietary treatment to avoid toxicity.

Question 21

Aromatic AAs

Answer 21

PHENYLALANINE, TYROSINE, TRYTOPHAN

Contain aromatic ring

Play a role in stabilizing the folded structure of many proteins.

Question 22

Phenylalanine

Answer 22

Essential, aromatic AAA

75% of phenylalanine is converted to TYROSINE in the LIVER by PHENYLALANINE HYDROXYLASE

Question 23

Tyrosine is a precursor for which 5 compounds?

Answer 23

1) Fumarate

2) Acetyl CoA

3) Dopamine —> Norepinephrine –> Epinephrine (all catecholeamines)

4) Thyroid hormones

5) Melanin (the protective pigment in the skin)

Question 24

PKU

Answer 24

Phenylketouria

Autosomal recessive disease resulting in dysfunctional PHENYLALANINE HYDROXYLASE enzyme, meaning that phenylalanine cannot be converted to tyrosine

Requires dietary restrictions on phenylalanine and products containing phenylalanine, such as aspartame.

Question 25

What is aspartame made up of?

Answer 25

Aspartate

Phenylalanine

With a methanol group

Question 26

What is Tryptophan a precursor for? (4)

Answer 26

An essential, aromatic AA

(1) SEROTONIN (important neurotransmitter in the brain, which can be further catabolized to melatonin).

(2) NICOTINAMIDE/NAPH (the conversion rate is ~67 mg of tryptophan to 1 mg nicotinamide).

(3) ACETYL COA (Kreb’s Cycle)

(4) PYRUVATE (Glucogenic)

Question 27

What is LYSINE catabolized to?

Answer 27

Lysine is a essential, ketogenic AA.

2 acetyl CoA & CARNITINE

Question 28

What is ARGININE catabolized to?

Answer 28

Alpha-ketoglutarate (Kreb’s Cycle intermediate)

ORNITHINE (very important intermediate of the UREA cycle)

Creatine

Nitric Oxide (important for vasodilation and potentially controlling BP).

Question 29

What is HISTADINE catabolized to?

Answer 29

Alpha-ketoglutarate

Histamine (protein found in the tissue and cells that are part of the allergic response)

CARNOSINE (Nitrogen containing non-protein that is found in muscle and brain tissue; it is believed to play a role in scavenging up ROS).

Question 30

Why is CARNITINE important?

Answer 30

It is important for FA transport in the MITOCHONDRIA, in order to get the FA over into the beta-oxidation pathway

Question 31

Methionine

Answer 31

Sulfer-containing AA

Question 32

Why is methionine important? (2 reason)

Answer 32

It serves as precursor for SAM (s-adenosylmethionine)