GI Tract Dysfunction Flashcards
Explain the steps in the p53 pathway (stressed cell)
- mdm2 doesn’t ubiquitinate p53
- so another kinase phosphorylates p53
- this leads to gene expression of p21
What are the role of monoclonal antibodies
- Block growth factor signals which tell cells to divide
- Carry cancer drugs or radiation to cancerous cells
- Block checkpoint inhibitors
- Mark the cancer cells, so immune cells can easily identify them
What type of radiation does a CT scan use
x ray
Mutations in DNA repair genes lead to what
A failure in repair, allowing subsequent mutations to occur
What is a prodrug
a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug.
What is the role of β catenin
cell adhesion at the adherens junction. It helps control the expression of genes and promotes the growth and proliferation, and differentiation of cells
What happens in G1 phase of cell cycle
Metabolic changes prepare the cell for division. At a certain point - the restriction point - the cell is committed to division and moves into the S phase.
What are the causes of IBD
It is unclear what the causes of IBD are, but a combination of genetics and immune system issues, where the immune system fights a pathogen, but attacks the GI tract lining too. NSAIDS and smoking are also common causes.
What causes type 2 diabetes
down-regulation of insulin receptors
What effects may RAS protein have
mitogenic functions:
- lipid metabolism,
- DNA synthesis,
- cytoskeletal organization.
What are the steps of recombinant protein production
- the cDNA from the gene of interest is inserted into and expression vector
- this is cloned into a suitable expression system
- the best construct/expression hosts are selected
What process is stimulated when blood glucose levels are too low
glycogenolysis in the liver and gluconeogenesis
Where are SGLT 2 transporters found
Proximal Tubule of Nephron
What are the three stimuli for gastric acid secretion
gastrin
histamine
Ach
How do MRIs work
uses a powerful magnet and radio waves. The machine creates a magnetic field around the patient and pulses radio waves into the area of the body being pictured. The radio waves cause the tissues in the body to resonate. These vibrations are translated into detailed 2D images captured by a special computer program.
Which cells secrete insulin
beta cells
What does the second checkpoint involve
signals which block activation of M phase until activation cyclin -CDK1 complex
What cell produces somatostatin
D cells
If a cell exists the cell cycle at the first restriction point, what happens
It goes into an arrested stage GO
How is type 1 diabetes managed
insulin injections
What is the ligand for DCC
netrin 1
What are the symptoms of IBD
- Pain, cramps or swelling in the tummy
- Recurring or bloody diarrhoea
- Weight loss
- Extreme tiredness
What part(s) of the GI tract does Crohn’s disease effect
any part of the digestive system, from the mouth to the anus
What is p21
a CDK inhibitor which stops the cell cycle proliferating
Where are DNA repair genes most active in the cell cycle
During G2
Where are glut 4 transporters found
Skeletal Muscle
Adipose Tissue
Heart
What is the electromagnetic spectrum
A continuous range of wavelengths. The types of radiation that occur in different parts of the spectrum have different uses and dangers - depending on their wavelength and frequency.
What is DCC
Deleted in Colorectal Carcinomas (DCC)
A receptor present on cell membrane, activating the MAP kinase cascade when phosphorylated.
Describe how proteins are absorbed by the body
Proteins are absorbed through the membrane, by transporters, or digested by e.g. amino pepsidase
When the parietal cell is resting, where are the H/K ATPases found
In vesicles inside the cell
What is the name for the removal of a drug from the plasma
Clearance
Where are SGLT 1 transporters found
Enterocyte of Intestinal Epithelium (luminal side)
If there is a presence of binding, what are the steps of wnt signalling
- The Wnt ligand (secreted glycoprotein) binds to Frizzled
- Frizzled becomes dishevelled
- This mutates the destruction complex
- No phosphorylation occurs and so the β catenin is stabilised
- Transcription is permitted (of proliferation genes)
What hormone inhibits gastric acid secretion
Somatostatin
Where are glut 1 transporters found
Blood
Blood-Brain Barrier
Heart
Which cells secrete glucagon
alpha cells
Describe how fats are absorbed by the body
- lipids emulsified by bile
- lipases break down triglycerides into FAs and monoglycerides
- FAs and MGs are packaged into miceltes and absorbed by the microvilli
- FAs and MGs are converted back to triglycerides
- triglycerides aggregate with cholesterol, proteins and phospholipids to form chylomicrons
- chylomicrons move into a lymph capillary, which transports them to the rest of the body
Where does ulcerative colitis effect
the colon
What process is stimulated when blood glucose levels are too high
glycogenesis
What is the function of gastric acid
to kill bacteria and aid digestions by solubilising food
In the cell cycle, what does cyclin E and CD2 interact to do
Promote the G1 to S phase transition
How would you treat IBD
immunosuppressants, amniosalicylates, antibiotics or biologics (antibody based treatment).
How do oncogeneic mutations affect RAS
make Ras insensitive to the state of the nucleotide, so it is continually switched “on.”
How are recombinant proteins made (simple)
the gene is isolated and cloned into an expression vector
Define drug targeting
the ability of the drug to accumulate in the target organ or tissue selectively and quantitatively, independent of the site and methods of its administration
Where are glut 2 transporters found
Liver
Pancreas
Small Intestine
What is the purpose of the cell cycle checkpoints
To regulate the cell cycle, and check for mistakes
What are glucose transporters
wide group of membrane proteins which facilitate the transport of glucose over a plasma membrane
What does a drug’s plasma half life depend on
how quickly the drug is eliminated from the plasma
What causes an increase in p53
DNA damage or other stressors
Define bioavaliability
the degree and rate at which an administered drug is absorbed by the body’s circulatory system, the systemic circulation.
When Rb is phosphorylated in the cell cycle, what happens
transcription factor E2F is activated, which promotes the expression of the cyclin E gene.
What is the function of the RAS proteins
deliver signals from cell surface receptors
Where are glut 5 transporters found
Enterocyte of Intestinal Epithelium (luminal side)
What are the 4 classes of cyclins
Cyclin A
Cyclin B
Cyclin D
Cyclin E
Where is the first restriction point of the cell cycle
Late G1
How is type 2 diabetes managed
Diet and lifestyle changes
What radiation do MRIs use
None
How do monoclonal antibodies work
by recognising and finding specific proteins on cancer cells.
What is an xray
uses radiation to produce images of the body. When the rays pass through the body, dense objects—such as bones—appear white on the film
If there is an absence of binding, what are the steps of Wnt signalling
- No ligand binds to frizzled
- APC, Axin and GSK-3β (The β catenin destruction complex) undergo phosphorylation
- β catenin acts as the transcription factor
- This then undergoes ubiquitination
- This is then under goes proteasomal degradation
- Transcription is inhibited
Which phase of the cell cycle does p53 prevent damaged DNA from entering
s Phase
What happens in M phase of cell cycle
A nuclear division (mitosis) followed by a cell division (cytokinesis).
What happens in G2 phase of cell cycle
Metabolic changes assemble the cytoplasmic materials necessary for mitosis and cytokinesis.
Other than bones, what can xrays be used to look at
other internal structures, such as organs. In this case, the patient may be given barium sulphate or dye to make the organs stand out more clearly in the X-ray image.
What are CT scans used for
takes a 360-degree image of internal organs, the spine, and vertebrae. Contrast dyes are often injected into the blood to make structures within the body more visible on the CT scan.
What is recombinant protein
Proteins that can result from the expression of recombinant DNA within living cells
Where are glut 3 transporters found
Brain
Neurons
Sperm
What is p53
A transcription factor, which acts as a tumour suppressor by regulating G1/S & G2/M checkpoints.
P53 regulates the expression of Mdm2 and the genes involved in growth arrest, DNA repair and apoptosis
If netrin 1 is present for DCC, what happens
if present acts as protooncogene
What is the main difference between type 1 and 2 diabetes
Type 1 diabetes is where the body doesn’t produce sufficient insulin, whereas 2 is where the body doesn’t respond to insulin production
Which cells in the stomach secrete gastric acid
Parietal cells
What is mdm2
a ubiquitin ligase
When in life does type 2 diabetes usually occur
adulthood
Explain the steps of MAP Kinase cascades
- Ligand binds to the receptor tyrosine kinase
- RTK dimerises and auto-phosphorylates
- GRB2 binds to the RTK
- SOS binds to GRB2
- GRB2 binds to Ras (which has GDP bound to it)
- SOS causes GDP to exchange to GTP, activating Ras
- Ras binds to MAPKKK Raf and helps activate it
- Raf phosphorylates and activates MAPKK Mek
- Mek phosphorylates and activates MAPK Erk
- Erk translocates to nucleus, activates transcription factors
Explain the steps in the p53 pathway (normal cell)
- Mdm2 ubiquitinates p53
2. this sends it for degradation
What causes type 1 diabetes
destruction of the beta cells
What do wnt proteins regulate
the proliferation of cells
What happens in S phase of cell cycle
DNA synthesis replicates the genetic material. Each chromosome now consists of two sister chromatids.
What effect does unbound DCC have
stimulates apoptosis
What is the name for the distribution of the drug in various body tissues
Volume of distribution
What do DNA repair genes code for
proteins whose normal function is to correct errors arising when cells duplicate their DNA prior to division
When in life does type 1 diabetes usually occur
during childhood
Where is the second restriction point in the cell cycle
Late G2
Describe how CHO is absorbed by the body
Polysaccharides are converted to disaccharides, which when transported into the cell with Na, are broken into monosaccharides and then into the capillary of the villi.
Where in collorectal epithelium is netrin 1 expressed
bottom of the villi
• Proliferation occurs at the base
• Apoptosis occurs at the tip, so the villi does not grow too large (decreasing polyp likelihood)
What happens when the first checkpoint is passed
CDK4 and Cyclin D interact, and phosphorylate Rb.
What are monoclonal antibodies
Antibodies that are made by identical immune cells that are all clones of a unique parent cell
Which CDK does cyclin D bind to?
CDK 4
Which CDK does cyclin E bind to?
CDK 2
Which CDK does cyclin A bind to?
CDK 1 or 2
Which CDK does cyclin B bind to?
CDK 1
