Theme 2- Module 4 (The Complex Proteome)

Question 1

What is the proteome?

Answer 1

The full number of proteins that are expressed by all the hereditary information in our DNA

Question 2

The double membrane of the nucleus is presumably evolved from what?

Answer 2

The membranous network of the single-membrane endoplasmic reticulum

Question 3

What is the benefit of compartmentalization?

Answer 3

Allows for a more intricate control in the regulation of cellular processes

Question 4

How will the pancreas respond to high levels of blood glucose in our body?

Answer 4

It will modulate the synthesis and secretion of an increased amount of insulin.

Question 5

What is insulin?

Answer 5

Effector protein that communicates with and produces a response on target cells; causes a drop in blood glucose levels

Question 6

Which type of cell makes insulin? Where are they located?

Answer 6

Beta islet cells

~ Pancreas

Question 7

Where is does glucose absorption occur most frequently?

a) The mouth
b) Small intestine
c) Large intestine

Answer 7

B: small intestine

Question 8

Across which structures does glucose absorption occur in the mouth?

Answer 8

Across thin epithelial surfaces with underlying blood vessels/capillaries

Question 9

Across which structures does glucose absorption occur in the small intestine?

Answer 9

Microvilli cells (that are also associated with very small blood vessels)

Question 10

How is insulin biosynthesis regulated?

Answer 10

Glucose metabolism

-> leads to an increase in insulin gene transcription and mRNA translation

Question 11

Where is the insulin protein produced? (be very specific)

Answer 11

Within the dense rough endoplasmic reticulum network of the beta cells in the pancreas

Question 12

Is insulin a small or large protein?

Answer 12

Small

Question 13

How many amino acids are in the translated polypeptide that is coded in the insulin gene?

Answer 13

110

Question 14

How many amino acids are in the functional insulin protein (that is secreted from beta cells)?

Answer 14

51

Question 15

Describe the structure of the functional insulin protein

Answer 15

Two amino acid chains

1) Alpha chain = 21 amino acids
2) Beta chain = 30 amino acids length.

These two amino acid chains form a dimer that makes up the functional insulin protein.

Question 16

The processing of the insulin protein from a single polypeptide of 110 amino acids to a protein structure containing 2 polypeptides of 21 and 30 amino acids is achieved by:

1) Pre- translational modifications.
2) Post- translational modifications.
3) Pre- transcriptional modifications.

Answer 16

2) Post- translational modifications.

Question 17

What is the 110-amino acid precursor of the mature insulin protein called?

Answer 17

Preproinsulin

Question 18

Preproinsulin is translated by bound ribosomes but processed within the endoplasmic reticulum. What process helps it translocate into the lumen of the rough ER?

Answer 18

An N-terminal signal sequence interacts with signal recognition particles to to facilitate translocation

The signal sequence is cleavaged

Question 19

Once the signal sequence is cleavaged, it yields which molecule?

Answer 19

Proinsulin

Question 20

After proinsulin is formed and before it is transported, what modifications occur?

Answer 20

Folding

Formation of three disulphide bonds

Question 21

True or false: proinsulin folds by itself, without any assistance

Answer 21

False

Requires the assistance of chaperone proteins in ER

Question 22

After proinsulin is folded, it is transported from the ER to ______

Answer 22

The Golgi apparatus,

Question 23

What happens to the proinsulin in the Golgi apparatus?

Answer 23

Further cleavage occurs

Forms the mature insulin dimer (containing both the A and B chains) releasing a small C-chain

Question 24

Why are the post-translational modifications of the preproinsulin peptide into the mature insulin protein crucial?

Answer 24

N- terminal and C-terminal amino acid residues (that were cleaved in the process) are needed to bind to the insulin receptors on the target cells

Question 25

List some possible post-translational modifications

Answer 25

• Cleavage
• Folding
• Disulphide bridge formation
• Covalent attachment of other molecules (phosphorylation, methylation and acetylation)

Question 26

What is phosphorylation?

Answer 26

Covalent attachment of a phosphate group to serine, threonine or tyrosine amino acid residues by enzymes called kinases

Question 27

Once the beta cells release insulin, what happens to the insulin effector molecules?

Answer 27

Bind to receptors that are expressed on specific target tissues

Question 28

What are receptors?

Answer 28

Proteins that receive and interpret information from such signalling molecules

Question 29

What family of receptors do insulin receptors fall into?

Answer 29

Receptor kinases

Question 30

Why is it important for insulin to bind to these receptors?

Answer 30

Enables many cells in our body to transport glucose across the plasma membrane into the cytosol of the cell

Question 31

True or false: receptor kinases exist in polymeric forms

Answer 31

False

Monomeric

Question 32

When a signal such as insulin binds to each receptor monomer on the extracellular surface of the cell, what happens?

Answer 32

Conformational change causes the receptor monomers to pair up (or dimerize)

Activation of cytoplasmic domains of the receptors–> engage in phosphorylation of specific amino acids (act like kinase proteins)

Question 33

The phosphorylation of many cytoplasmically situated receptor kinase domains leads to what?

Answer 33

The binding and activation of other important cytoplasmic proteins

Question 34

The intracellular signal leads to what?

Answer 34

The activation of glucose transporter proteins at the cell surface (+ the absorption of glucose into the cell)

Question 35

The binding and activation of other important cytoplasmic proteins leads to what?

Answer 35

Activation of a series of diverse transducer and amplifier proteins that are downstream from the activated receptor
—> intracellular signal

Question 36

How is the initiation and maintenance of intracellular signals regulated?

Answer 36

Positive-feedback loops —> signal on

Negative- feedback loops —> signal termination

Double- negative feedback —> inhibitor of the signal is also inhibited

Question 37

In what form do the fat cells in adipose tissue store the excess glucose and fatty acids?

Answer 37

Fats in the form of triglycerides

Question 38

Liver and muscle cells are able to take up glucose from the blood and store the excess as ______

Answer 38

Glycogen

Question 39

In order to produce more than one mRNA transcript from a single protein-coding gene, what must occur?

Answer 39

Alternative splicing of pre-mRNAs

Question 40

What happens during alternative splicing?

Answer 40

Some exons are excluded during the splicing process (being removed much like the introns)

Question 41

Why does alternative splicing occur?

Answer 41

What the spliceosome recognizes as an exon in some primary transcripts, can be identified as an intron in OTHER primary transcripts

Question 42

True or false: alternative-splicing forms are always produced in different cell types

Answer 42

False

Can be in the same cell as well

Question 43

What is the modification that helps skeletal muscle cells use glucose faster than liver cells?

Answer 43

Alternative splicing:

Skeletal: Exon 11 removed from mature mRNA

Liver: Exon 11 kept in

Question 44

How does the presence/absence of exon 11 affect the cells?

Answer 44

Absence leads to the translation of a higher affinity version of the insulin receptor –> able to mount a higher response of glucose uptake in response to an insulin signal

Question 45

Once blood glucose levels are returned to resting levels, what happens? (Describe termination)

Answer 45

Negative feedback loop:

• drop in blood glucose detected by the pancreatic cells
• decrease in the secretion of insulin

Question 46

If the insulin protein were not processed correctly following translation, what could’ve happened?

Answer 46

A lack of ability for this protein to bind to the insulin receptors on target tissues

Question 47

If the insulin receptor isoform was incorrectly spliced during mRNA processing, what could’ve happened?

Answer 47

No ability to activate glucose transport proteins that allow for the import of glucose from the blood stream at these target regions

Question 48

A defect in either the insulin protein or the insulin receptor can lead to what?

Answer 48

The inability to take up glucose, resulting in hyperglycemia and eventually diabetes