Amino Acid Catabolism Flashcards
is the catabolism of Amino Acids a preferred method of energy generation?
No. It is only done in extreme circumstances
Amino Acids …
- 20 different ones
- Act as precursors to other nitrogen-containing biologically important compounds like hormones and neurotransmitters
- Can be used as an energy source
What are the three major steps in Amino Acid Catabolism?
- Removal of the amino group. (deamination) done via:
- i) transamination (transfer of amino group to alpha-ketoglutarate, producing glutamate)
- ii) Oxidative deamination (Removal of amino group from glutamate to release ammonia)
- iii) Other Deamination Processes - Enter the Urea Cycle (Conversion of NH3 to Urea for secretion)
- Metabolic breakdown of Carbon skeleton to generate common intermediates that can be catabolized to CO2 or or used in anabolic pathways to be stored as glucose or fat .
What is transamination and how does it differ between different Amino Acids?
The transfer of an amino group to a-ketoglutarate to produce glutamate.
“Transaminases” or “Aminotransferases” are the enzymes that allow this to occur. They all require Pyridoxal-5-phosphate (PLP)
Each amino acid has its own aminotransferase that enables the amino group transfer
What is Oxidative deamination?
in the liver, the amino group of glutamate is released as ammonia. This regenerates a-ketoglutarate and is done via the enzyme Glutamate Dehydrogenase
This enzyme requires NADP+ or NAD+ as a cofactor. This is the only enzyme known to allow each as a cofactor
The enzyme is allosterically inhibited by GTP and activated by ADP
How is excess Ammonia transported?
Excess ammonia is toxic to animal tissues by itself.
Glutamine synthase catalyses the synthesis of Glutamine by adding ammonia to glutamate at the expense of ATP
Glutamine is a non-toxic carrier of ammonia and travels through to the liver or kidneys by blood
In liver or kidney mitochondria, glutamine is converted to glutamate and ammonia. The ammonia gets incorporated into the urea cycle.
What is the Glucose-Alanine Cycle?
Alanine is produced in muscle tissues by transferring excess glutamate to pyruvate.
Alanine is also able to safely transport ammonia through the blood.
What is the Carbamoyl-Phosphate Synthase-1 Reaction?
Ammonia released from oxidative deamination is incorporated into Carbamoyl phosphate by using ATP and bicarbonate
Carbamoyl phosphate enters the urea cycle in the mitochondria
What are the 5 enzymes in the Urea Cycle?
Carbamoyl Phosphate Synthase
Ornithine Transcarbamoylase Citruline
Argininosuccinate Synthase
Argininosuccinase
Arginase
What are 3 possible therapies for patients with defects in the Urea Cycle?
- A defined diet containing only the most minimal amount of essential amino acids
- Feed the patients Benzoate or phenylacetate. These compounds react with Glycine and Glutamine respectively and form non-toxic compounds which are secreted in urine.
- For patients with N-acetylglutamate synthase deficiency, Carbamoyl Glutamate can act as an activator of carbamoyl phosphate synthase
How is the Urea Cycle regulated?
- Enzymes involved in the Urea Cycle are synthesized in higher levels only when proteins begin to be utilized for energy production. (at the point of starvation)
- Carbamoyl Phosphate Synthase is allosterically activated by N-acetylglutamate
What are 4 diseases that affect Amino Acid Catabolism?
- PKU (Phenylketonurea)
- Maple Syrup Urine Disease
- MMA (Methylmalonic Acidemia)
- Alkaptonuria
What is PKU (Phenylketonurea)?
This disease is caused by a defect in the catabolism of phenylalanine.
Specifically, caused by defective phenylalanine hydroxylase.
Symptoms and effects include Neonatal vomiting and mental retardation.
What is Maple Syrup Urine Disease?
Specifically caused by defecting a-keto acid dehydrogenase complex.
If left untreated, the patient will not survive past 4. Causes buildup of branched chain keto-acid. Symptoms and effects include: Urine smelling like maple syrup, vomiting, convulsions, mental retardation, and early death.
Treatment includes removal of affected Amino Acids from diet. (Isoleucine, Leucine, Valine
What is MMA (Methylmalonic Acidemia)?
Caused by defect in Methyl Malonyl CoA Mutase (MMM)
Symptoms and effects include: Vomiting, convulsions, mental retardation, and early death
Treatment includes a controlled diet:
- sufficient protein and lots of glucose and fat
- Removal of Threonine, Isoleucine, Methionine, and Valine
- Remove large chain fatty acids
