Nitrogen DLA 2

Question 1

Summarize glucose-alanine cycle in a fasting state

Answer 1

In the fasting state: The glucose-alanine cycle

• When in the fasting state, muscle protein is degraded.

• Some amino acids go to liver for gluconeogenesis
• Some amino acids are consumed in the muscle for energy
• Means there will be an excess amount of nitrogen in muscle

Question 2

What happens when there is excess N in the musxle?

Answer 2

When there is excess N in the muscle:

• Pyruvate formed by glycolysis may be transaminated to alanine (in the muscle)
• Alanine may be transported to the liver in the blood.
• Alanine is transaminated to pyruvate in the liver
• Pyruvate is converted to glucose (gluconeogenesis) • Glucose released into the blood for the body
• Therefore:
• Alanine is an important transport form of ammonia from the muscle
• Glucose-alanine cycle takes care of excess muscle nitrogen during any state, but is especially active during fasting and starvatio

Question 3

What does Alanine transaminase enzyme do?

Answer 3

Alanine transaminase enzyme (ALT)
- Takes the nitrogen off of alanine and puts the N onto a-KG (pyruvate and glutamate
are formed (reaction is reversible)
- Takes the nitrogen off of glutamate and puts that N onto pyruvate (a-KG and alanine
are formed.

• Alanine is an important transport form of amino acid (and nitrogen) from the muscle (important during starvation)
• Alanine (pyruvate) is an important precursor for gluconeogenesis during starvation
• Glucose-alanine cycle involves the muscle (where alanine is formed) & liver (site of gluconeogenesis)

Question 4

Summarize aspartate metabolism

Answer 4

• Upon transamination, aspartate is converted to oxaloacetate (precursor of gluconeogenesis)
• Aspartate (ASP) is used for synthesis of Asparagine (ASN)
• Asparagine is the amide derivative of ASP
• Glutamine is the N-donor for asparagine synthesis (not free NH3)
• Humans have three, and only three enzymes which can fix free ammonia to a carbon containing molecule

• We have not discussed any of these yet (by the way)
• Asparaginase is used in the treatment of some leukemia patients.
- Reduced availability of asparagine to the tumor cells inhibits growth of the cance

Question 5

Explain glutamate metabolism

Answer 5

• Glutamate and glutamine are important sources of ammonia for the urea cycle
• Glutamate dehydrogenase catalyzes an Oxidative deamination reaction (requires NAD+)
- Glutamate DH may also operate in the reverse direction (reductive amination, and incorporate an NH3/NH4+
directly onto α-KG
• Glutamate & α-ketoglutarate are essential components of most transaminase reactions
• Glutamine Synthetase is important for scavenging NH3/NH4+ from circulation
- ImportantintheBrain
- Also important in endothelial cells of the Hepatic vein to ensure that any NH3/NH4+ exiting the liver is captured before entering circulation

• Glutamine is a non-toxic, transport form of ammonia from the peripheral tissues

• Renal tissue is rich in Glutaminase which can provide ammonia for acid base homeostasis in renal
tubule (when needed)

• Glutamate dehydrogenase reaction is reversible and can be used for the synthesis of glutamate from α- KG especially when tissue ammonia/ammonium levels are high