Protein Metabolism I (Lecture 3 - Exam 3) Flashcards
AAs are the source of XXXXXX consumed in the diet. What is it used for?
NITROGEN
Used for protein synthesis and synthesis of nitrogen containing non-protein compounds
How are AAs classified?
Several ways:
Essential & Non-essential (and conditional), or
Glucogenic & Ketogenic
Explain catabolism of AAs.
(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
Glucogenic AAs
Catabolism yields pyruvate or an intermediate of the Krebs Cycle
Ketogenic AAs
ONLY LEUCINE & LYSINE (which are also essential)
Catabolism yields acetoacetate, acetyl CoA, acetoacetyl CoA
Is alanine glucogenic or ketogenic?
GLUCOGENIC
Is asparagine glucogenic or ketogenic?
GLUCOGENIC
Explain the catabolism of asparagine.
ASPARAGINE is a non-essential AA. This is an example of a transamination reaction.
ASPARAGINE ———–> ASPARTATE ————> OAA
Asparaginase Aminotransferase (PLP/B6 dependent)
Asparaginase
Enzyme that converts ASPARAGINE to ASPARTATE by removing the NH3 (Nitrogen) group from asparagine
Aminotransferase
Enzyme that converts ASPARTATE to OAA, requires PLP/B6.
Explain the role of alpha-ketoglutarate in asparagine catabolism.
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.
What is another example of a transamination reaction?
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.
How are AAs catabolized?
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).
What are the 4 potential products of the carbon skeleton from AA catabolism?
(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
BCAAs
LEUCINE, ISOLEUCINE, VALINE
–The only essential AAs that undergo transamination
–Amino group has branch chain
–Primarily catabolized in the muscle versus the liver
Where are BCAAs mainly catabolized?
MUSCLE
Explain BCAA catabolism.
(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.
BCKD complex
BRANCHED CHAIN ALPHA KETO ACID DEHYDROGENASE complex
What are the end products of BCAA catabolism?
ACETYL COA
SUCCINYL COA
ACETOACETATE
GLUTAMINE
ALANINE
Maple Syrup Urine Disease
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.
Aromatic AAs
PHENYLALANINE, TYROSINE, TRYTOPHAN
Contain aromatic ring
Play a role in stabilizing the folded structure of many proteins.
Phenylalanine
Essential, aromatic AAA
75% of phenylalanine is converted to TYROSINE in the LIVER by PHENYLALANINE HYDROXYLASE
Tyrosine is a precursor for which 5 compounds?
1) Fumarate
2) Acetyl CoA
3) Dopamine —> Norepinephrine –> Epinephrine (all catecholeamines)
4) Thyroid hormones
5) Melanin (the protective pigment in the skin)
PKU
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.
What is aspartame made up of?
Aspartate
Phenylalanine
With a methanol group
What is Tryptophan a precursor for? (4)
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)
What is LYSINE catabolized to?
Lysine is a essential, ketogenic AA.
2 acetyl CoA & CARNITINE
What is ARGININE catabolized to?
Alpha-ketoglutarate (Kreb’s Cycle intermediate)
ORNITHINE (very important intermediate of the UREA cycle)
Creatine
Nitric Oxide (important for vasodilation and potentially controlling BP).
What is HISTADINE catabolized to?
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).
Why is CARNITINE important?
It is important for FA transport in the MITOCHONDRIA, in order to get the FA over into the beta-oxidation pathway
Methionine
Sulfer-containing AA
Why is methionine important? (2 reason)
It serves as precursor for SAM (s-adenosylmethionine)
