14_Biochem Block 3.6 Dietary Amino Acids/degradation I

Front 1

Describe the relative number of E genes for the ubiquitin system and why its set up that way.

Back 1

1. About 10 E1 genes.
2. About 100 E2 genes
3. About 600-700 E3 genes.
E3 proteins have fine specificity for specific proteins. E2 binds with less, but significant specificity to various E3 molecules. E1 is quite promiscuous and binds to most E2 proteins and is the link between target proteins and proteasome.

Front 2

Describe the proteasome the structure of the proteasome.

Back 2

There's a cap and a lid on both ends that recognize the Ubiquinated protein. There are two alpha rings, each composed of 7 enzymes (total 14) that straighten the protein, break disulfide bonds, and regulate. Their are two central Beta rings that each have 7 enzymes (total 14) with different specificities.

Front 3

How large are the fragments of ubiquitin degradation? What happens to them after that?

Back 3

7-9 aa long. These are subject to amino- and carboxy- terminal degradation that produces free amino acids.

Front 4

What's wrong in 12yo patients with Parkinsons?

Back 4

Parkin, an E3-ubiquitin-ligase is defective and does not recognize target proteins. The protein accumulates, aggregates, and destroys dopaminergic neurons in the CNS substantia nigra pars compacta region of the brain - resulting in the characteristic tremors associated with Parkinson's Disease.

Front 5

Describe how HPV interferes with the ubiquitin system to cause carcinoma. (p292)

Back 5

HPV encodes for a E3-ubiquitin ligase that recognizes p53. p53 suppresses tumors in mammalian cells. Bc p53 is incorrectly degraded, cancers arise.

Front 6

How does htt (huntingtin) protein interfere with the ubiquitin system to cause neurodegenerative disease?

Back 6

A mutation in htt cause it to be an inhibitor of the proteasome instead of being degraded. Proteins accumulate and deposition within the brain causes degeneration.

Front 7

dietary proteins are degraded in the: by:

Back 7

Stomach by endo- and exo-proteases.

Front 8

What do chief cells secrete?

Back 8

Pepsinogen

Front 9

Before proteins can be degraded, pepsinogen must be activated. To what is it degraded to and by what?

Back 9

Pepsinogen is degraded to pepsin by low pH in stomach

Front 10

What types of cells secrete HCl?

Back 10

Parietal cells.

Front 11

The N-terminal region of Pepsinogen blocks the active site. How is it removed?

Back 11

When the protein experiences low pH, it undergoes a conformational change that allows the N-terminal region to be cleaved and released - unblocking the active site.

Front 12

What does pepsin cleave?

Back 12

N-terminal side of large hydroPHOBIC amino acids such as Isoleucine, Phenylalanine, Valine.

Front 13

The acinar cells of the pancreas synthesize three protease zymogens:

Back 13

1. Trypsinogen
2. Proelastase
3. Chymotrypsinogen

Front 14

How/where are the pancreatic zymogens activated? And at what pH? (p293)

Back 14

In the duodenum at pH7:
1. Trypsinogen is degraded to Trypsin by enteropeptidase located on the surface of the small intestine and active when cleaved from the membrane
2. Trypsin is then used to degrade Proelastase to Elastase and;
3. Chymotrypsinogen to Chymotrypsin

Front 15

What neutralizes the pH of stomach acids as it enters the duodenum?

Back 15

Bicarbonate.

Front 16

Describe the activity of Trypsin:
1. What is characteristic of the AA it cleaves?
2. What two examples were given in class?
(p294)

Back 16

1. Cleaves long-chain residues
2. Lysine and Arginine.

Front 17

Describe the activity of Elastase:
1. What is characteristic of the AA it cleaves?
2. What examples were given in class and which side of the aa does it prefer to cleave?
3. What sequence requirement does it have/prefer

Back 17

1. The aa have short chains
2. Glycine and Alanine - prefers to cleave after its target sequence
3. It also prefers to cut after two aa in a row.

Front 18

Describe the activity of Chymotrypsin:
1. What is characteristic of the AA it cleaves?
2. What examples were given in class.

Back 18

1. They have large side chains
2. Phenylalanine, Tyrosine, Tryptophan

Front 19

What is the difference between Endo- and Exo-peptidases? (p294)

Back 19

Endopeptidases cleave at specific locations anywhere along a peptide chain.
Exopeptidases cleave at only the amino or carboxy terminal ends to produce free, di- or tri-peptides.

Front 20

What produces Carboxypeptidases? Aminopeptidases?
**What activates carboxypeptidase?

Back 20

Carboxypeptidases are made by the pancreas (activated by Trypsin)
Aminopeptidases are made by the intestine

Front 21

What are class transporters? (p295)

Back 21

They are specific for different types of amino acids. They pick up Di- and Tri-peptides and free amino acids. Free amino acids are picked up by Acidic, Basic, Neutral, Small, Di- and Tripeptide, and Aromatic transporters.

Front 22

When di- and tripeptides are picked up the cells, how are further degraded to free amino acids? (p295)

Back 22

Via amino- and carboxypeptidases.
**NOTE: Dysfunctional absorption transporters can result in disease.

Front 23

What three amino acids are released into the serum by the liver as a source of energy (10% of the energy usage, in fact)

Back 23

LIV: Leucine, Isoleucine, Valine

Front 24

Since amino acids are not stored, how are they used?

Back 24

For energy

Front 25

As amino acids are degraded, what is the fate of the ammonia? (297)

Back 25

It is transferred to alpha-ketoacids to form amino acids that function as ammonia transport molecules, to take ammonia to the liver for urea synthesis.

Front 26

In PKU, what enzymes are deficient? What is used instead?

Back 26

Deficiency in Phenylalanine Hydroxylase or Dihydrobiopterin Reductase. Instead, Aminotransferase is used but this creates toxic products.

Front 27

Aromatic amino acid transporter deficiency causes symptoms similar to:
Why and what are the symptoms

Back 27

Pellagra. This is a deficiency in tryptophan and symptoms include the four D's: Diarrhea, dementia, dermatitis, death