Big boy Flashcards
explain luminal, mucosal and post absorptive phases of protein digestion
- *luminal phase**
- stomach: pepsin released by pepsinogen (zymogen / proenzyme). pepsinogen is activated by HCl, which is releaed from parietal cells in the gastric pits.
- small intestine: further digestion from pancreatic enzymes
mucosal phase:
- brush border enzyme: enterokinase converts trypsinogen -> trypsin
then:
trypsin activates:
a) chymotrysinogen -> chymotrypsin
b) procarboxypetidae -> carboxypeptidase
- a.a. enter the epithelial cells via Na-linked secondary active transport across the apical membrane (same system for sugar)
- *post-absorptive phase;**
- a.a. transporte across basolateral membrane by fac. d
what do two starting materials do you need before glycogen synthesis?
what do you convert one of ^ into for glycogen synthesis (and how)?
what is the mechanism of glycogen synthesis? (3)
- *glycogen synthesis needs:**
- a primer (protein that glucose will attach to): glycogenin.
- glucose-6-phosphate (G6P)
BUT: NEED TO CONVERT G6P -> UDP-glucose before can be added to glycogen:
- *a) G6P –> G1P
b) G1P –> UDP-glucose** - *glycogen synthesis:**
- UDP-glucose added to glycogenin primer initially, and then non-reducing ends of glucose by enzyme glycogen synthase to create a glycosidic-1-4 bonds
- the UDP is lost and one glucose is added onto the glycogen
- branches are made by branching enzyme: creates a 1-6 glycosidic bonds
whats the MoA of insulin
- activating phosphodiesterase?
- activating protein phosphastase?
1. - insulin activates phosphodiesterase
- phosphodiesterase breaks down cAMP -> AMP
- this means protein kinase A is not activated
- this means that glycogen synthase is not phosphorylated and not switched off
- glycogen synthase: glucose -> glycogen
AND
- phosphorlase kinase is not active: glycogen phosphorylase not activated = glycogen break down inhibited
2. insuline activates protein phosphatase -> downstream consequences also: - glycogen synthase: glucose -> glycogen
crohns diease:
a) definition
b) active disease symptoms? (4)
c) leads to? (4)
d) diagnosis? (2)
- *crohns diease:
a) definition: chronic inflammation condition that can affect whole GIT, but usualy found localised to small bowel** - *b) active disease symptoms:**
- diarrhoea
- abdominal pain
- fatigue
- fever
- blood in stool (sig. finding)
- *c) leads to:**
- scarring of bowel epithelium
- ulcers
- fistulas (hole in bowel)
- bowel obstruction
- *d) diagnosis:**
- fecal calprotectin
- colonscopy
which cells regulate water contents in the gut?
what is the mechanism of this?
secretory cells of the intestinal crpyts:
- CFTR channel within these cells controls this:
a) Cl- moves from ECF via Na/K/CL2 cotransporter (as does Na & K)
b) Cl- enters lumen through CFTR channel
c) Na+ is reabsorbed into ECF via Na/K ATPase
d) negative Cl- in lumen attracts Na by paracellular pathway (through cell gaps)
e) water follows the Na into the lumen
explain the genetic changes caused by hypoxia on:
HIF-1
VEGF
- *HIF-1: Hypoxia-Inducible Factor**
- transcription factor up-regulated in presence of hypoxia
- hypoxia causes stabilisation of HIFa subunit which then binds to promoters in DNA. This causes:
i) Down-regulates mitochondria (via autophagy)
ii) Promotes VEGF expression - *VEGF: Vascular Endothelial GF**
- Promotes growth of vasculature, namely, capillaries providing muscle tissue.
- This improves blood supply and, consequently, oxygen supply, countering the effects of hypoxic conditions.
PFK1
EPO
explain the genetic changes caused by hypoxia on:
PFK1
EPO
- *PFK1: Phosphofructokinase-1**
- key rate controlling enzyme in glycolysis (and hence, also the Cori Cycle).
- up-regulation improves the speed of glycolysis and hence, the rate of ATP production in the absence of oxygen
- *EPO: Erythropoietin**
- produced at the kidneys
- in response to chronic hypoxia, results in increased red blood cell production and hence increased haematocrit.
explain mechanism of how insulin is released from B langerhan cells
- glucose enters B langerhan cells through glucose transport GLUT 1&3
- glucokinase (converts glucose to glucose-6-phosphate) acts as gluocse sensor for insulin secretion
- high Km of glucokinase ensures that the initation of of insulin secretion by glucose only occurs when blood glucose levels are high
- glucose converted to glucose-6-phosphate and to pyruvate & generates ATP through ECT = increases ATP:ADP ratio
- increased ATP:ADP ratio: closes ATP-sensitive K channel on B cell
- causes voltage-gated Ca2+ channels open: Ca moves into the cell
- high intracellular Ca2+ triggers insulin secretion !
explain the main mechanism of insulin action to allow glucose into the cell !
when not enough insulin:
- IRS (adaptor protein) & PI3K (lipase kinase) & Akt (protein kinase) are all in the cytoplasm and inactive. causes:
- GLUT4 transporters are stored intracellularly. (cant get glucose across (or LOTS of glucose across)
- glucose cant cross membrane
when enough insulin:
- insulin binds to tyrosine-kinase receptor: causes autophosporylation of tyrosine-kinase receptor:
- IRS can bind to the phosphorylated receptor: causes IRS to be phosphorylated
- when IRS is phosphorylated, PI3K binds to IRS-P and PI3K becomes phosphorylated.
- phosphorylatedPI3Kcauseschange in membrane lipid: PIP2 –> PIP3
- PIP3 causes activation of Akt
- Akt causes change of GLUT4, to be inserted into membrane = les glucose through !
explain the different phases of luminal, mucosal and post-absorptiave phase of carb digestion x
- *•Luminal phase:**
- Large polysaccharides broken down to shorter molecules via salivary and pancreatic amylase (starch à dextrins and maltose)
-Mucosal phase:
Brush borden enzymes (e.g. sucrase, lactase, maltase, limit dextrinase and glucoamylase) break down molecules into glucose and galactose
Glucose enters enterocytes via the SGLT1/2 transporters
•Post-absorptive phase:
Sugars exit basolateral membrane via facilitated diffusion (GLUT 1/2 transporters)
explain the WHOLE mechanism of gut homing -> up to IgA interacting with bacteria and viruses
Gut specific homing:
- activated B and T cells leave Peyer’s patches and move to lamina propria. They are targeted to different regions of the gut to provide effective immune response.
- Gut dendritic cells produce retinoic acid (vitamin A) which induce gut homing T cells to express α4β7 and CCR9.
- Epithelial cells lining gut home T cells by expression of CCL25 (ligand for CCR9) while endothelial cells express MadCAM (ligand for α4β7).
.After binding, activated immune cells produce IgA (secretory antibody).
- IgA is actively transported across epithelium by polymeric Ig receptor
- Epithelial cells express secretory component on its surface-
-
.IgA/IgM binds to secretory component via J-chain and enters the cell via endocytosis at basal membrane
4. IgA is secreted into lumen via exocytosis at apical membrane
In the lumen IgA agglutinates viruses and bacteria
explain mechanism of CD diease occuring
Celiac disease
- Gliadin resists being broken down by any sorts of enzyme in the small intestine
- When it gets to small intestine, it binds on secretory IgA in mucosal membrane which helps protect enterocytes from toxins and pathogens
- IN COELIAC DISEASED PATIENTS, the IgA along with gliadin do not get broken down and are transferred from the apical membrane of the enterocytes down to the basolateral membrane
- This is done because on the apical membrane there is overexpression off Transferrin receptor (TFR) which is usually used to transport iron
- Now the gliadin molecule is in lamina propria
- Here enzyme called tissue transglutaminase (tTG) remove amide group from gliadin to form DEAMIDATED GLIADIN
- Then this deamidated gliadin is taken up by macrophages
- The gliadin is presented on the cell surface membrane by MHH: They either have HLA-DQ2 or HLA-DQ8
- The macrophages present gliadin via MHC to CD4 T cells which in turn release inflammatory cytokines like IFN-γ which destroys epithelia of small intestine
- CD4 T cells also activate B cells to produce IgA anti-gliadin, anti-tTG and anti-endomysial* (EMAs)
- CD4 T cells also recruit CD8 T cells which further destroys epithelia of small intestine
•
explain malate cycle
- to get from from pyruvate –> phosphoenolpyruvate (PEP) need: malate cycle:
1. pyruvate + CO2 —> oxaloacctate (via enzyme: pyruvate carboxylase - uses ATP). BUT oxaloacctate cannot leave the mt. so:
2. oxaloacctate + NADH + H –> malate + NAD+
- malate leaves the mt, and then gets converted back to oxaloacctate:
* *malate + NAD+ –> oxaloacctate** (via enzyme: cytostolic malate dehydrogenase) - oxaloacctate + GTP (now in cytosol) —> PEP + CO2 (via enzyme: cystolic PEP carboykinase)
expain cori cycle x
cori cycle:
when anaerobic & @ muscle during glycolysis = glucose -> pyruvate -> lactate by lactate deyhdroganse.
lactate goes to liver: oxidised back to glucose by gluconeogensis
glucose sent back to muscle to do work.
repeat xox
no net synthesis of glucose here - just recycling the carbons !
