Lecture 9 - Amino Acid Catabolism 2 Flashcards
What does high levels of glutamate cause?
Increased water in brain cells through osmosis, causing swelling of the brain leading to a coma
What is NH3 converted to and where does the conversion take place?
- Urea
- Liver
What do organisms need to have to produce urea from arginine?
Arginase
What are the 2 compartments of the urea cycle?
1) Carbamoyl phosphate acts as a carrier in the mitochondrial matrix
2) NH2 enters the urea cycle in the cytosol through the conversion of ornithine to citrulline
What is required to make urea?
2 NH3; one from glutamate and one from aspartate
Describe the asparate-argininosuccinate shunt
Argininosuccinate is split into arginine (which continues the urea cycle) and fumarate (which is converted to malate and then enters TCA cycle)
What can deficiencies in urea cycle enzymes lead to?
- Mental retardation (partial deficiency)
- Early death (mutation in both genes)
- NH3 build up
What can an NH3 buildup cause?
- Activation of glutamate dehydrogenase and glutamine synthetase
- Loss of ATP (decreases TCA cycle intermediates)
- Increase in glutamate
What is the treatment for a deficiency in urea cycle enzymes?
Low protein diet
What happens to alpha-keto acids?
They are ultimately converted in acetyl CoA that is used in TCA cycle
Generally describe the threonine/glycine/serine/alanine pathway
- Threonine is converted to acetyl CoA by 2 pathways
1) Threonine -> glycine -> serine -> pyruvate -> acetyl CoA
2) Threonine -> acetaldehyde -> acetate -> acetyl CoA
What can a deficiency in acetaldehyde dehydrogenase cause?
Alcohol intolerance
Which enzymes can convert alanine to pyruvate?
Alanine transaminase and alanine dehydrogenase
What is FH4?
- Tetrahydrofolate
- Can transfer one carbon in many oxidation states
What are the 3 oxidation states of tetrahydrofolate?
1) N5, N10-methenyl FH4
2) N5, N10-methylene FH4
3) N5-methy FH4
What enzyme converts N5, N10-methenyl FH4 and N5, N10-methylene FH4 between each other and what is the cofactor?
- Methenyl FH4 reductase
- NADH + H+ -> NAD+
What enzyme converts N5, N10-methylene FH4 and N5-methy FH4 between each other and what is the cofactor?
- Methylene FH4 reductase
- NADH + H+ -> NAD+
What is the function of N5, N10-methenyl FH4?
Purine biosynthesis
What can N5, N10-methylene FH4 act on?
Purines, pyrimidines, and amino acids
What can N5-methy FH4 act on?
Amino acids
Generally describe the phenylalanine/tyrosine pathway
Phenylalanine is converted to tyrosine, which is then converted to acetyl CoA by either acetoacetate or fumarate
How is fumarate converted to acetyl CoA?
Fumarate -> malate -> oxaloacetate -> pyruvate -> acetyl CoA
What is phenylketonuria?
A genetic disease in which phenylalanine hydroxylase enzyme is absent, therefore the body is unable to metabolize phenylalanine to tyrosine
What occurs in phenylketonuria instead of phenylalanine metabolism?
Phenylalanine is transaminated to phenylpyruvate, which accumulates in the blood and is excreted in the urine
Why are phenylalanine and phenylpyruvate harmful?
- They interfere with normal brain and nerve cell development
- Phenylalanine competes with other amino acids for uptake in the brain
What can elevated phenylalanine levels cause?
Lighter skin colour because the increased phenylalanine inhibits melanin synthesis from tyrosine
Which enzyme converts tyrosine to melanin?
Tyrosinase
What can phenylpyruvate be converted to?
Phenylacetate or phenyllactate
