Amino Acid Degradation Flashcards
In the fed state, what are amino acids primarily used for?
synthetic processes
In the fasting state, what are amino acids primarily used for?
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.
During the fasting state, what stimulates skeletal muscle to mobilize amino acids by breaking down proteins?
cortisol. Remember that skeletal muscle does not have glucagon receptors.
What amino acids can be used to make propionyl CoA (which can be converted to succinyl CoA)
isoleucine (can also be converted to acetyl-CoA and enter the TCA that way), valine, and methionine
Which amino acids can be used to make a-ketogluterate?
primarily glutamate
What other AAs can make glutamate? (which can then be converted to a-ketogluterate to enter the TCA)
1) arginine and proline can make it through a glutamate-semialdehyde intermediate
2) histidine
3) glutamine (reversible)
Which AAs can be used to make OAA?
aspartate and asparagine
NOTE: These two are used for the urea cycle and synthesis of purines
How can phenylalanine, tyrosine, and leucine enter the TCA cycle?
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
How can lysine and tryptophan enter the TCA cycle?
they can both be converted to a-ketoadipate, which can be converted to acetoacetyl-CoA, which can then be converted to acetyl-CoA
What are the main carriers of nitrogen in the blood
alanine and glutamine
What are the branched-chain amino acids?
Leu, Ile, Val; they are used for ENERGY in peripheral tissue- aka they are not going to be high in the blood
Which of the following AAs will typically be in high concentration in the blood?
1) glutamine
2) valine
3) isoleucine
4) alanine
5) leucine
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
T or F. All 20 amino acids can be broken down into pyruvate, acetyl-CoA or a citric acid cycle intermediate
T
What happens to AAs before they are used for energy?
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
What are the two ways to remove an amino group from an amino acid?
- Transamination moves amino group between keto acids (In general, funnels amino groups into glutamate)
- Deamination removes amino group as free ammonia.
What enzyme family facilitates transamination?
aminotransferases or transaminases
What cofactor is required for transamination reactions?
Pyridoxal phosphate (PLP) is a cofactor in transamination reactions.
NOTE: PLP is also a cofactor for some decarboxylation reactions
What is PLP derived from?
PLP is derived from vitamin B6.
T or F. Transamination reactions are readily reversible and are used in both amino acid synthesis and amino acid degradation.
T.
NOTE: Glutamic acid and a-ketogluturate are involved in many transamination reactions
What AAs cannot perform transamination?
Lysine and Threonine
Deamination of amino acids requires what?
input of water and NADP+. (generates an oxidized AA, NADPH, and a free ammonia group)
Aminotransferases as diagnostic markers of liver disease or dysfunction
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
How do the branched-chain AAs enter the TCA cycle?
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
In high energy states, what can a-keotgluterate be converted to?
glutamate (which can be converted to glutamine for nitrogen transport)
What is Maple syrup urine disease (MSUD) (aka Branched-chain ketoaciduria) caused by?
Consequences? Clinical Manifestation?
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
What is the mode of inheritance of MSUD?
autosomal recessive (~1:180,000)
What five AAs can yield alanine when degraded?
Cysteine, Glycine, Serine and Threonine (all via Pyruvate) and Tryptophan directly
Alanine itself is also a source of Alanine
What four AAs can yield glutamine when degraded?
Arginine, Proline and Histidine (via Glutumate) and Glutamate directly
Glutamine itself is also a source of Glutamine
What is methionine used for?
Used for synthesis of Cysteine, SAM
What are Tyrosine and Phenylalanine
used for?
Used for synthesis of melanin (pigment), dopamine and epineprhrine (catacholamine), tyroxine (hormones)
What is the fate of alanine deposited from skeletal muscle into the bloodstream?
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
What are the steps of the Glucose-Alanine cycle?
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
What are glucogenic AAs?
Amino acids carbon skeletons that form pyruvate or a citric acid cycle intermediate and can be used in gluconeogenesis
What are ketogenic AAs?
Amino acids carbon skeletons that form acetyl-CoA and can be used to form fatty acids or ketone bodies
What AAs are ketogenic only?
Leucine and Lysine
What AAs are Ketogenic AND Glucogenic?
Isoleucine, Threonine, Phenylalanine, Tryrosine, and Tryptophan (last three are aromatic side-chains)
all 13 others are glycogenic only
What is the fate of glutamine in the bloodstream?
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
What are the fates of a-ketogluterate in the kidney?
1) TCA cycle
2) convert to glucose
3) convert to serine or alanine
