Lecture 12 Flashcards
(14 cards)
Protein turnover
Breaking p.p chains to a.a then using those a.a to build another protein. Varies between tissue (2% in muscle, 15% in intestine). But, muscle is greatest bulk of protein.
Amino acid processing
During starvation: Low insulin levels cause the body to break down proteins into amino acids for energy.
Normal conditions (protein turnover): Old or damaged proteins are broken down. The resulting amino acids are reused to build new proteins.
Excess amino acids: When we consume more protein than needed, or when amino acids aren’t reused, they are oxidised for energy since they cannot be stored.
issue is that the amine group needs to be detoxified and there’s a carbon skeleton (O2 to CO2 and ATP, gluconeogenesis or FA synthesis). Protein cannot be stored.
Principles
Liver coordinates a.a processing and is the first place a.a travel to via hepatic portal vein. Also performs urea cycle, gluconeogenesis and lipogenesis which detoxifies amine group and processes carbon backbone. Backbone may also be oxidised forming CO2 and ATP. No interconversion of backbones. Degradation enzymes have a very high Km (not rate limiting), therefore, only affected by [a.a]. Excess [a.a] degraded.
After feeding
Portal vein’s a.a composition is the same as the food we consume. 20% branched chain a.a. Hepatic vein will have 70% branched chain a.a meaning that the liver has used most of the unbranched a.a and left the branched ones. Veins from muscles will have little branched a.a as they are used for energy in muscles.
Glucose-alanine cycle
glucose to pyruvate which then picks up an amine group forming alanine which travels to the liver to enter urea cycle.
During starvation
High [alanine] leaving the muscles and the alanine picks up the amine groups from the branch chain a/a and other a.a burnt as fuel. What’s left is a pyruvate that can enter gluconeogenesis during starvation.
Transanimation
Alpha-keto can be used to make fat (non starvation) or gluconeogenesis.
Urea cycle
Glutamate, alanine and asparate a.a help introduce amine groups in urea cycle. Costs heap of ATP to convert ammonia to urea. Like Krebs where it has a carrier. Not efficient especially if we’re breaking down proteins.
Processing skeletons
Can feed into Krebs. Typically an intermediate of the Krebs can be used for gluconeogenesis while the others able to be converted into FA synthesis or ketone bodies.
a.a synthesis
Humans can’t produce most a.a, therefore, we rely on bacteria to do it for us. Always tied to central pathway of metabolism. They can steal from glycolysis, gluconeogenesis or Krebs to build a.a and hence, proteins.
Other products from a.a
- Creatine
- Non-peptide hormones
- nucleotides
Purine rings
Requires lots of ATP and a.a to build a single purine nucleotide. Billions of purines needed to be synthesised for cell division which cells can recycle from other dead cells.
Inhibitors of purine synthesis
Purine synthesis is complex as it requires ATP, folate, a.a therefore salvage pathways are useful. Cancer cells grow quickly and uncontrollably meaning it needs billions of purines and pyrimidines. Hence, it tries to salvage it. If it needs to build some, it uses the enzyme PRPP. So meds aim to block it by looking like a purine but not being able to be used to build DNA. But, it also kills any other cell trying to replicate
Prine degradation
When energy charge reduces therefore in energy crisis. To stay alive, it will break down and O2 AMP. It forces that reaction to the right to produce AMP. Common in cancer patients. Causes build-up of uric acid which crystalises in joints. Immune system launches inflammatory response (gout). Allopurinol decreases blood [uric acid] preventing the build-up. Also, in alcoholics.
