Ch. 21 Amino Acid Metabolism Flashcards
Give a brief description of dietary protein digestion
Dietary Protein Digestion
- begins in the stomach (which is a very acidic environment)
- Acidic environment-favors protein denaturation into random coils, which makes the protein more accessible for proteolysis
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Proteolytic enzymes-which degrade proteins into their component amino acids, that can then be absorbed by the intestine and transported in the blood.
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Example of a proteolytic enzyme
- pepsin-main protease, nonspecific & maximally active at pH 2
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Example of a proteolytic enzyme
Describe how enzyme half-lives vary, including enzymes that occupy important metabolic control points.
Enzyme half lives
- Half lives range from a few min→weeks→more
- Most rapidly degrading (Short 1/2 lives) enzymes are important metabolic control points
- Most slowly degrading (Long 1/2 lives) enzymes have constant activity underall conditions
What is the role of lysosome in protein degradation?
When does lysosome participate in nonselective and selective degradation?
Lysosomes:
Role in Protein Degradation:
- Lysosomes degrade substances the cell takes up by endocytosis
- basically they chop it all up, they degrade many proteins
- Lysosomes = “gut of the cell”
- normally nonselective
- contain ~50 hydrolytic enzymes
- internal pH~5; enzymes have an acidic pH optima
Nonselective Degradation? When?
- Well nourished cells are nonselective.
Selective Degradation? When?
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Starving cells are selective.
- avoid degradation of essential amino acids
- the rate of degradation depends on the protein’s sequences
What is the role of ubiquitin in protein degradation?
What are the three steps involved in protein ubiquitination?
Ubiquitin in Protein Degradation
Role of Ubiquitin in Protein Degradation
- Ubiquitin selectively marks the proteins for degradation (the process is called ubiquitination)
Three Steps of Protein Ubiquitination:
- Ubiquitin-activating enzyme (E1): via hydrolysis of ATP, the carboxyl end of Ub is linked to a Cys residue of E1
- Ubiquitin-condensing enzyme (E2s): the activated Ub is transferred to the second enzyme by attaching it to a Cys residue of E2
- Ubiquitin-protein ligases (E3s): the activated Ub is transferred to the protein to be degraded.
!!! BUT…For a protein to be efficiently degraded it has to have a polyubiquitin chain.
***in order for a protein to be degraded, it must contain a polyubiquitin chain.
What does the rate a protein turns over depends on?
Give some examples
Protein Turnover Rate
Rate a protein turns over (turnover involves degradation and synthesis) depends on its sequence
Know the 3 examples:
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N-end rule
- The ½ life of a cytosol enzyme is determined by its N-terminal residue
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Amino acid composition
- Many E3s have a variety of ubiquitination signals that occur in specific target proteins
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Cyclin destruction boxes
- Specific amino acid sequences that mark cyclin proteins for destruction.
- Cyclins control the progression of the cell cycle and are selectively degraded thru ubiquitination at specific stages of the cycle.
- Specific amino acid sequences that mark cyclin proteins for destruction.
Describe the parts of the 26S proteasome and their basic function.
26S Proteosome
Main function of the 26S proteasome is where the ubiquitinated proteins are degraded
It has two parts:
- 20S Proteasome: hollow core where proteins are hydrolyzed into amino acids (Central part of the 20S proteasome
- 19S Cap: entry point of proteins into the 20S proteosome; regulates the entry of proteins into the 20S proteosome
Describe the pathway for proteasome-mediated protein degradation, including the roles of ubiquitin and ATP.
Pathway for proteasome-mediated protein degradation:
(use ubiquitin and ATP to explain)
Ubiquitin…
Ubiquitin…for you to be degraded you need to be marked with a chain
- Ubiquitin marks proteins with polyubiquitin chain
Use ATP to…
- To recognize the ubiquitinated chains (oh you have a chain, come in)
- To unfold the substrate in order for it to be able to enter the 20S proteasome
