Theme 2- Module 4 (The Complex Proteome) Flashcards
What is the proteome?
The full number of proteins that are expressed by all the hereditary information in our DNA
The double membrane of the nucleus is presumably evolved from what?
The membranous network of the single-membrane endoplasmic reticulum
What is the benefit of compartmentalization?
Allows for a more intricate control in the regulation of cellular processes
How will the pancreas respond to high levels of blood glucose in our body?
It will modulate the synthesis and secretion of an increased amount of insulin.
What is insulin?
Effector protein that communicates with and produces a response on target cells; causes a drop in blood glucose levels
Which type of cell makes insulin? Where are they located?
Beta islet cells
~ Pancreas
Where is does glucose absorption occur most frequently?
a) The mouth
b) Small intestine
c) Large intestine
B: small intestine
Across which structures does glucose absorption occur in the mouth?
Across thin epithelial surfaces with underlying blood vessels/capillaries
Across which structures does glucose absorption occur in the small intestine?
Microvilli cells (that are also associated with very small blood vessels)
How is insulin biosynthesis regulated?
Glucose metabolism
-> leads to an increase in insulin gene transcription and mRNA translation
Where is the insulin protein produced? (be very specific)
Within the dense rough endoplasmic reticulum network of the beta cells in the pancreas
Is insulin a small or large protein?
Small
How many amino acids are in the translated polypeptide that is coded in the insulin gene?
110
How many amino acids are in the functional insulin protein (that is secreted from beta cells)?
51
Describe the structure of the functional insulin protein
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.
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.
2) Post- translational modifications.
What is the 110-amino acid precursor of the mature insulin protein called?
Preproinsulin
Preproinsulin is translated by bound ribosomes but processed within the endoplasmic reticulum. What process helps it translocate into the lumen of the rough ER?
An N-terminal signal sequence interacts with signal recognition particles to to facilitate translocation
The signal sequence is cleavaged
Once the signal sequence is cleavaged, it yields which molecule?
Proinsulin
After proinsulin is formed and before it is transported, what modifications occur?
Folding
Formation of three disulphide bonds
True or false: proinsulin folds by itself, without any assistance
False
Requires the assistance of chaperone proteins in ER
After proinsulin is folded, it is transported from the ER to ______
The Golgi apparatus,
What happens to the proinsulin in the Golgi apparatus?
Further cleavage occurs
Forms the mature insulin dimer (containing both the A and B chains) releasing a small C-chain
Why are the post-translational modifications of the preproinsulin peptide into the mature insulin protein crucial?
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
List some possible post-translational modifications
- Cleavage
- Folding
- Disulphide bridge formation
- Covalent attachment of other molecules (phosphorylation, methylation and acetylation)
What is phosphorylation?
Covalent attachment of a phosphate group to serine, threonine or tyrosine amino acid residues by enzymes called kinases
Once the beta cells release insulin, what happens to the insulin effector molecules?
Bind to receptors that are expressed on specific target tissues
What are receptors?
Proteins that receive and interpret information from such signalling molecules
What family of receptors do insulin receptors fall into?
Receptor kinases
Why is it important for insulin to bind to these receptors?
Enables many cells in our body to transport glucose across the plasma membrane into the cytosol of the cell
True or false: receptor kinases exist in polymeric forms
False
Monomeric
When a signal such as insulin binds to each receptor monomer on the extracellular surface of the cell, what happens?
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)
The phosphorylation of many cytoplasmically situated receptor kinase domains leads to what?
The binding and activation of other important cytoplasmic proteins
The intracellular signal leads to what?
The activation of glucose transporter proteins at the cell surface (+ the absorption of glucose into the cell)
The binding and activation of other important cytoplasmic proteins leads to what?
Activation of a series of diverse transducer and amplifier proteins that are downstream from the activated receptor
—> intracellular signal
How is the initiation and maintenance of intracellular signals regulated?
Positive-feedback loops —> signal on
Negative- feedback loops —> signal termination
Double- negative feedback —> inhibitor of the signal is also inhibited
In what form do the fat cells in adipose tissue store the excess glucose and fatty acids?
Fats in the form of triglycerides
Liver and muscle cells are able to take up glucose from the blood and store the excess as ______
Glycogen
In order to produce more than one mRNA transcript from a single protein-coding gene, what must occur?
Alternative splicing of pre-mRNAs
What happens during alternative splicing?
Some exons are excluded during the splicing process (being removed much like the introns)
Why does alternative splicing occur?
What the spliceosome recognizes as an exon in some primary transcripts, can be identified as an intron in OTHER primary transcripts
True or false: alternative-splicing forms are always produced in different cell types
False
Can be in the same cell as well
What is the modification that helps skeletal muscle cells use glucose faster than liver cells?
Alternative splicing:
Skeletal: Exon 11 removed from mature mRNA
Liver: Exon 11 kept in
How does the presence/absence of exon 11 affect the cells?
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
Once blood glucose levels are returned to resting levels, what happens? (Describe termination)
Negative feedback loop:
- drop in blood glucose detected by the pancreatic cells
- decrease in the secretion of insulin
If the insulin protein were not processed correctly following translation, what could’ve happened?
A lack of ability for this protein to bind to the insulin receptors on target tissues
If the insulin receptor isoform was incorrectly spliced during mRNA processing, what could’ve happened?
No ability to activate glucose transport proteins that allow for the import of glucose from the blood stream at these target regions
A defect in either the insulin protein or the insulin receptor can lead to what?
The inability to take up glucose, resulting in hyperglycemia and eventually diabetes
