Lecture 21

Question 0

What is type 2 Diabetes Mellitus?

Answer 0

Type 2 diabetes is characterized by insulin resistance. At first, your pancreas makes extra insulin to make up for it. But, over time it isn’t able to make enough insulin and glucose levels rise.

Question 1

What is type 1 Diabetes Mellitus?

Answer 1

Type 1 Diabetes is caused by a loss of beta cells in pancreatic islets of Langerhans. It is also known as juvenile diabetes because it occurs mainly in children and young adults. It is insulin-dependent because patients rely on insulin to alleviate their high levels of glucose

Question 2

What are complications of untreated diabetes?

Answer 2

1) vascular disease (angiopathy)

2) micro vascular disease leads to damage to eyes (retinopathy), kidneys, and nerves

Question 3

Where are ribosomes found within a cell?

Answer 3

1) free floating in the cytosol

2) bound to the exterior of the rough endoplasmic reticulum

Question 4

What is a signal recognition particle (SRP)?

Answer 4

An SRP recognizes end terminal (N-terminus) signal sequences on cytosol proteins that are being synthesized (not a very specific sequence; it is simply composed of hydrophobic amino acids); blocks elongation by folding until it finds a receptor molecule on an ER lumen ribosome and resumes elongation. This is called cotranslational protein translocation (secretion)

Question 5

When does cotranslational protein translocation occur?

Answer 5

Once a protein being synthesized in the cytosol reaches about 65-70 amino acids in length

Question 7

What are three examples of protein destinations post-translation from proteins that are made in the rough ER?

Answer 7

1) ER membrane - stop-transfer signal allows protein to remain in ER
2) Lysosomal enzymes - mannose-6-phosphate attachment
3) Secretion - no additional signal needed (default)

Question 8

What are three examples of protein destinations post-translation from proteins that are made in the cytosol?

Answer 8

1) Nucleus - nuclear localization signal (basic amino acid sequence), importins, Ran proteins
2) Peroxisomes - peroxisomal targeting sequences, PTS receptors
3) Mitochondria - N-terminal leader (20-80 charged aa’s) translocation complexes

Question 9

What is the Zellweger syndrome caused by?

Answer 9

Mutations in genes required for peroxisome targeting or function

Question 10

How many proteins used by mitochondria are actually made by the mitochondrial genome?

Answer 10

Only 13. The rest (several hundred) are made in the cytosol from nuclear-encoded mRNAs

Question 11

Amino acid modifications are:

Answer 11

1) Enzyme-catalyzed or spontaneous
2) Reversible or irreversible
3) Multiple roles: Structural, Functional, & Regulatory

Question 12

What does a “perm” essentially do to your hair?

Answer 12

Modifies keratin by reorganizing disulfide bridges (about 14% of keratin contains cystine)

Question 13

What is the difference between cystine and cysteine?

Answer 13

Cysteine is an amino acid that contains sulfur. When two cysteine combine their sulfur elements to form a disulfide bridge, the residue is now called cystine

Question 14

What is the most common type of post-translational modification to proteins?

Answer 14

Phosphorylation:

1) frequently used to control enzyme activity
2) specific sites
3) catalyzed by kinases, using ATP
4) reversible by phosphatase action
5) changes protein structure
6) can increase or decrease activity

Question 15

Phosphorylation of each of the following is inhibitory or stimulatory?

a) eIF2
b) eIF4E
c) 4E-BP

Answer 15

a) inhibitory
b) stimulatory
c) stimulatory

Question 16

Where does acetylation and methylation occur on proteins?

Answer 16

On histones of lysine and arginine

Question 17

What are characteristics of an individual with Multiple Sulfatase Deficiency (MSD)?

Answer 17

It is a genetic disease characterized by progressive paralysis, skeletal deformities, & neurological defects. Infants develop slowly and lose abilities after age 1.

Question 18

What causes Multiple Sulfatase Deficiency (MSD)?

Answer 18

Primary defect is in sulfatase-modifying factor-1 gene (SMF-1) required to modify an essential Cys in the active site of sulfatases

Question 19

Why does Multiple Sulfatase Deficiency (MSD) combine the enzyme deficiency and phenotypic features of several diseases?

Answer 19

MSD disables SMF-1 from properly modifying any of the cysteine residues, whereas in other Sulfatase Deficient disorders, only a specific cysteine residue is affected

Question 20

What is a nutritional deficiency of selenium linked to?

Answer 20

1) Dilated cardiomyopathy
2) Congestive heart failures
3) Striated muscle degeneration
4) Weakness (Keshan Disease)

Question 21

Most selenoproteins catalyze what type of reactions?

Answer 21

Oxido-reduction reactions

1) Glutathione peroxidase - reduces peroxides
2) 5’-deiodinases - activates thyroxine

Question 22

What does glutathione peroxidase do?

Answer 22

1) Destroys reactive and damaging H2O2
2) Reduces organic peroxides R-OOH to R-OH
3) Uses Glutathione (G-SH) as a reducing agent

Question 23

What does 5’-deiodinase do?

Answer 23

1) Dietary iodide is activated
2) Tyrosine residues in thryoglobulin are iodinated
3) Condensation then protein cleavage reactions release mainly thyroxine (T4)
4) T4 is converted to T3 (more active form) by 5’-deiodinase

Question 24

How does a selenocysteine amino acid incorporate itself into an amino acid chain co-translationally (What is recoding)?

Answer 24

1) Selenium is phosphorylated by ATP to make selenophosphate
2) A serine residue with a tRNA specific for serine combines with selenophosphate to form a selenocysteine amino acid with its tRNA
3) The selenocysteine amino acid then binds to a UGA stop codon, causing it to recode and allow the selenocysteine residue to become part of the amino acid chain

Question 25

What is the function of Vitamin K?

Answer 25

Vitamin K is required for blood clotting & mediates gamma-carboxylation. (K stands for koagulation)

Question 26

What inhibits Vitamin K function?

Answer 26

Warfarin (Coumadin), dicoumarol, and other coumarins

Question 27

What is protein glycation?

Answer 27

1) Non-enzymatic reaction of glucose with protein amino groups (N-terminal alpha NH2 / internal lysine epsilon-NH2)
2) Can change protein function - contributes to diabetes pathogenesis

Question 28

How does protein glycation relate to diabetes?

Answer 28

HbA1C is glycated on N-terminal valine of Beta chains (irreversible binding)

Question 29

What is the difference between glycation and glycosylation?

Answer 29

There is enzymatic glycosylation which is part of the post-translational modifications of proteins and there is non-enzymatic glycosylation (ie glycation). Glycation is a form of protein damage as glycated proteins have reduced functionality. Glycosylation on the other hand is important for proteins to become functional.

Question 30

What is the function of HbA1C for physicians?

Answer 30

It is a marker of blood sugar levels in patients with diabetes (higher blood sugar = higher HbA1c). It is a good marker because it does not just measure the instantaneous levels of blood sugar, but it measure the time average levels of blood sugar (3-6 week development). Normal levels = 4-6%; >7% = DM

Question 31

What does HbA1C have to do with diabetes complications?

Answer 31

High levels of glucose cause glycation to various proteins (lots of damage). This process is called Advanced Glycation End-products (AGE). Therefore, when HbA1C blood levels are high, there is much damage occurring to other glycated proteins as well

Question 32

What are conditions in which false low HbA1C values arise?

Answer 32

Diseases/conditions in which RBCs live shorter than 120 days (normal length of life). This can include sickle cell disease, etc.

Question 33

What are conditions in which false high HbA1C values arise?

Answer 33

Diseases/conditions in which RBCs live longer than 120 days (normal length of life)