Amino Acid Degradation and Urea Cycle Flashcards
*Understand how amino acids are degraded (i.e. removal of amino group, conversion of the
carbon skeleton)
amino acids are degraded by removing nitrogen, metabolizing alpha-ketoacids, so carbon skeletons can enter metabolic pathway as precursors of glucose or citric acid cycle intermediates
Beware of the fact that liver cannot deaminate branched amino acids. What are the branched aa ?What organ utilizes these amino acids as energy?
Liver CANNOT deaminate branched amino acids.
Branched amino acids-Valine, Leucine, Isoleucine
MUSCLE uses branched-chain amino acids as FUELS (energy) The nitrogen from these amino acids are transported to the liver by the glucose alanine cycle.
*Understand how nitrogen is transported from muscle to liver. What are the two principal transport mechanisms?
The muscle does not have enzymes for Urea cycle (like liver does, so nitrogen must be transported from muscle to liver.
Nitrogen is transported to liver through ALANINE and GLUTAMINE paths.
*Be familiar with the steps of the urea cycle
Urea cycle occurs in the liver;
Steps:
1. Carbamoyl and Ornithine react (by ornithine transcarbamoylase) to form citrulline
2. Citrulline (transported to cytoplasm) condenses with Aspartate to form argininocsuccinate (cleaving ATP into AMP) by Argininosuccinate synthetase.
3. Argininosuccinate then cleaved into arginine and fumarate (by argininosuccinase enzyme)
4. Arginine then hydrolyzed (cleaved by water) to generate UREA and ornithine (which is transported back to mitochondria for another cycle) by enzyme arginase.
*Understand the difference between ketogenic and glucogenic amino acids.
Ketogenic aa- are amino acids metabolized to acetyl CoA and acetoacetyl CoA. They can PRODUCE ACETYL CoA for the CAC and form FATS (but NOT glucose)
Glucogenic aa- aa degraded to the remaining major intermediates, and CAN be used to synthesize GLUCOSE.
Where are amino acids obtained from?
What is the purpose of degrading cellular proteins to aa’s?
What happens to excess Amino acids and why?
Amino acids are obtained from the diet when proteins are digested
Cellular proteins are degraded to aa because of damage or for regulatory purposes.
excess amino acids are degraded, because aa are NOT stored.
What is the first priority use of amino acids?
The first priority use of amino acids are as PRECURSORS for PROTEINS or other biomolecules.
What are the amino acids that are solely ketogenic?
LEUCINE and LYSINE
ketogenic aa only enter pathways as Acetyl CoA
which amino acids can be both ketogenic and glucogenic?
Isoleucine, Threonine, Tryptophan, phenylalanine and tyrosine can be both keto and glucogenic.
Differentiate between how ketogenic and glucogenic aa enter pathways.
If aa enters as acetyl CoA- Ketogenic
if aa enters as pyruvate- glucogenic
glucogenic also go through alpha-ketoglutarate, succinyl coa, fumarate, oxaloacetaate and PEP (phosphoenolpyruvate pathway).
How are the carbon skeletons of degraded amino acids metabolized?
The carbon skeletons of amino acids are metabolized to seven major metabolic intermediates: pyruvate, acetyl CoA , Acetoacetyl CoA, alpha-ketoglutarate, succinyl CoA, fumarate and oxaloacetate.
What organ is the site of urea synthesis? What occurs if there are defects in the urea cycle enzymes?
What causes liver damage and what can result because of this?
LIVER is the site or urea synthesis.
Defects in urea cycle enzymes result in elevated levels of NH4+ in the blood. Elevated blood NH4+ causes nervous system malfunction and can be lethal
Liver damage is caused by excessive alcohol consumption that can be fatal in part because liver is unable to synthesize Urea and consequently NH4+ appears in the blood.
What are the pathologies and effects of excessive alcohol consumption?
Effects of excessive alcohol consumption:
Fatty liver develops- causing INCREASE in NADH (which inhibits catabolic pathways, stimulates anabolic)
Alcoholic hepatitis- inflammation of the liver (inhibit metabolism of liver), cause cell death, increase in acetaldehyde (reversible, liver can be regenerated)
Cirrhosis- fibrous, scarring tissue; liver becomes destroyed, no regeneration, IRREVERSIBLE
What happens with excess NH4+? What are these organisms called?
Excess NH4+ is converted into Urea by the urea cycle (in liver).
Organisms that excrete excess NH4+ as urea are called ureotelic organisms.
In humans, the urea cycle occurs in the LIVER
What occurs in the glucose alanine cycle?
In the glucose alanine cycle:
During prolonged exercise and fasting: muscle uses branched-chain amino acids as fuel. The nitrogen from these amino acids are then transferred (through glutamate) to ALANINE, which is released into blood stream. In liver, alanine is taken up and converted into pyruvate for the synthesis of glucose.
