Sem 4 molecules and mechanisms

Question 1

Gastrin

Answer 1

Released from G cells in crypts of Liberkuhn (antral mucosa) response to stretching of stomach wall and presence of protein in stomach. Inhibited by secretin, CCK, GIP and somatostatin.
Function: activates ECL cells to secrete histamine, inc acid release from parietal cells. enhances activity of pyloric pump, promoting stomach emptying by inc gastric motility. Inc growth of gastric mucosa.

Question 2

secretin

Answer 2

released from S cells in crypts of liberkuhn (duodenal mucosa) in response to gastric acid in duodenum - low PH. Stimulates release of watery bicarbonate ions from pancreatic and bile epithelium + in duodenum. reduces acid secretion from stomach by inhibiting gastrin release from g cells through somatostatin. stimulates pepsinogen from parietal cells. stim release glucagon insulin oancreatic polypeptide and somatostatin.

Question 3

cholecystokinin CCK

Answer 3

released from I cells in duodenum and jejunal mucosa in response fatty substances and proteoses in chyme. Inhibits gastric emptying, reduces acid decretion from stomach by inhibiting gastrin release from G cells through somatostatin. stimulatess acinar cells of pancreas to release digestive enzymes, inc production of bile, contraction of gall bladder and relac sphincter of Oddi so bile delivered duodenum.

Question 4

Gastric inhibitory peptide

Answer 4

releasaed from K cells in duo and jejunal mucosa in response to fatty substances and glucose in chyme. Weakly dec GI motility so weakly inhibits stomach emptying. Weakly reduces acid secretion from stomach by inhibiting gastrin release from G cells through somatostatin. stimulates insulin if hyperosmolarity of glucose in duodenum as incretin hormone.

Question 5

GLP-1

Answer 5

released from L cells in duo and jejunal mucosa in respnce fatty substances and glucose in chyme. stimulate release of insulin if hyperosmolarity of glucose in duodenum as an incretin hormone.

Question 6

somatostatin

Answer 6

released from D cells in crypts of Lieberkuhn (duo mucosa) and in pancreatic islets in response excess gastric acid in stomach and duodenum. inhibited by vagal stimulation. dec acid secretion by inhibiting G cells, ECL cells and parietal cells. dec pepsinogen sec. dec pancreatic and SI fluid secretion, dec gall bladder contraction thus reducing bile delivery to duodenum. Dec release of insulin and glucagon.

Question 7

pepsinogen

Answer 7

released from peptic/chief cells in stomach, from stimulation of cells by Ach (vagal) and responce to acid. Inactive form of pepsin, activated into by HCL, pepsin is proteolytic enzyme that works in acidic conditions.

Question 8

pepsin

Answer 8

activated from pepsinogen, activation inc by inc pepsinogen release. used in protein digestion

Question 9

HCL

Answer 9

released from parietal/oxyntic cells in stomach, inc by histamine-ECL cells, Ach and gastrin. Inhibited by somatostatin, GIP, prostaglandinE2, Secretin. Makes the conditions in the stomach acidic. Allows breakdown of food.

Question 10

intrinsic factor

Answer 10

released from parietal/oxyntic cells in stomach. Essential for absorption of vit B12 in distal ileum. It binds to vit b12 to protect from being digested in stomach, complex reaches terminal ileum where IF binds to receptor and vit b12 is absorbed. Autoimmune destruction of parietal cells leads to deficiency in intrinsic factor which can cause pericious anaemia.

Question 11

bicarbonate ions

Answer 11

released from mucosal cells and brunners glands in duodenum. secretion inc by secretin. Inhibited by substance P. it neutralises acid and transported in mucus that covers gastric epithelium

Question 12

mucus

Answer 12

released from mucous surface cells in stomach in responce to contact with food or iritation.

Question 13

prostaglandin E2 PGE2

Answer 13

inhibited by NSAIDS like aspirin. Inc secretion of bicarbonate ions, dec acid secretion. Gi pathway. this is why can cause peptic ulcers as excess acid secretion.

Question 14

histamine

Answer 14

released from ECL cells in responce to reduced acid secretion, secretion inc by gastrin and Ach. Inhibited by H2 receptor antagonists. increases acid secretion via H2 receptors on parietal cells. works via opposite intracellular pathway-Gs to PGE2 to inc acid.

Question 15

trypsinogen

Answer 15

From acinar cells of pancreas, activated by enterokinase into trypsin. Inhibited by trypsinogen inhibitor. its the zygomen of trypsin, activated by enterokinase, activated autocatalytically by trypsin.

Question 16

trypsin

Answer 16

result from activation of trypsinogen. stoped by trypsinogen inhibitor. Involved in protein digestion.

Question 17

enterokinase

Answer 17

from the epithelial cells of intestine. activates trypsinogen into trypsin

Question 18

chymotrypsinogen

Answer 18

released from acinar cells in pancreas. inhibited by trypsinogen inhibitor. inactive form of chymotrypsin, activated by trypsin.

Question 19

chymotrypsin

Answer 19

result of activation of chymotrypsinogen. inhibited by trypsinogen inhibitor. protein digestion.

Question 20

procarboxypolypeptidase

Answer 20

released from acinar cells of pancreas, inhibited trypsinogen inhibitor. inactive form of carboxypolypeptidase, activated by trypsin.

Question 21

carboxypolypeptidase

Answer 21

as a result of activation of procarboxypolypeptidase. inhibited trypsinogen inhibitor. Protein digestion.

Question 22

pancreatic amylase

Answer 22

released from acinar cells of pancreas. digestion (hydrolysis) of starches, digestion/hydrolysis of starches, glycogen and other carbs except cellulose to form mostly disaccharides and a few trisaccharides

Question 23

pancreatic lipase

Answer 23

released from acinar cells of pancreas. Digestion (hydrolysis) of neutral fat into fatty acids and monoglycerides.
This is the main enzyme that caused the breakdown of fats, following emulsification

Question 24

cholesterol esterase

Answer 24

released from acinar cells of pancreas. digestion/hydrolysis of cholesterol esters

Question 25

phospholipase

Answer 25

released from acinar cells of pancreas. digestion of fatty acids to form phospholipids

Question 26

trypsin inhibitor

Answer 26

released from acinar cells in pancreas. Prevents the activation of trypsin both inside the acinar cells and the ducts of the pancreas.
This prevents the digestion of the pancreas itself.
Dysfunction of trypsinogen inhibitor can cause acute pancreatitis.

Question 27

lactase

Answer 27

released from enterocytes lining villi of SI. splits lactose into galactose and glucose.

Question 28

sucrase

Answer 28

released from enterocytes lining villi of SI. split sucrose into fructose and glucose.

Question 29

Maltase

Answer 29

Released from enterocytes lining villi of SI. split maltose into multiple molecules of glucose.

Question 30

A-dextrinase

Answer 30

released from enterocytes lining villi of SI. split small glucose polymers into multiples molecules of glucose

Question 31

peptidase (aminopolypeptidase) (dipeptidase)

Answer 31

In membrane of microvilli of brush border in SI. They split large polypeptides into tripeptides and dipeptides and a few into amino acids.
The breakdown products of polypeptides are transported through the microvillar membrane to the interior of the enterocyte.
There are more specific peptidases inside the enterocyte.
Once the peptides have been broken down into amino acids, they enter the blood from the basolateral membrane of the enterocyte

Question 32

Lingual lipase

Answer 32

from lingual glands in mouth. Lingual lipase is swallowed with saliva into the stomach. It digests fats/triglycerides in the stomach.

Question 33

bile salts and lecithin

Answer 33

found in bile. Emulsification of fats:
These surround fat globules.
These allow the globule to be fragmented into small, more water soluble globules.
This allows pancreatic lipase (a water soluble enzyme) to breakdown the fat globules into fatty acids and monoglycerides.
Bile salts form ‘micelles’ around these products and transport them to the brush border for absorption.

Question 34

ras

Answer 34

Ras is involved in cell signalling.
Normally, it is bound to GDP and so inactive.
Upon binding with GTP, it becomes active.
Once active, it initiates a cell signalling cascade, leading to:
Inhibits apoptosis
Promotes cell growth
Promotes protein synthesis
Ras is an oncogene protein

Question 35

Wnt (B catenin, APC, GSK-3B)

Answer 35

Wnt is a growth factor, involved in Wnt signalling.
When Wnt doesn’t bind to a cell, GSK-3B (and APC) keep B-catenin phosphorylated and so B-catenin is degraded.
When Wnt binds to the receptor on the cell, GSK-3B has no effect on B-catenin and so it is not phosphorylated and not degraded.
B-catenin can now enter the nucleus, cause transcription of Cyclin D, which then activates CDK4.
The cell has now entered the cell cycle.

Question 36

cholesterol

Answer 36

produced by the liver. It is used in the formation of bile acids and salts.
Cholesterol is converted to primary bile acids in the liver, which is then transported to the duodenum via bile

Question 37

bile acids/salts

Answer 37

produced by the liver and duodenum. Primary bile salts are synthesised from cholesterol.
They are transported to the duodenum via bile, where they undergo bacterial action and are converted into secondary bile acids.
Secondary bile acids conjugate into bile salts.
Bile salts cause emulsification of fats.

Question 38

a keto acid

Answer 38

produced by the liver. Involved in transamination.

A keto-oxygen is transferred to an amino acid to make a new α-keto acid and a new amino acid.

Question 39

ferritin/apoferritin

Answer 39

Iron is stored in the liver as ferritin.

Ferritin binds to apoferritin in the liver, which allows it to be stored.

Question 40

Bilirubin, urobilinogen, urobilin, stercobilinogen, stercobilin

Answer 40

unconjugated-spleen. conjugated-liver. Bilirubin is a breakdown product of haemoglobin and is excreted in bile. RBC breakdown produces globin and heme. Heme is split into pyrrole nuclei, which are converted into biliverdin. Biliverdin makes unconjugated bilirubin. Unconjugated bilirubin is transported to the liver by binding to albumin. Hepatocytes take up unconjugated bilirubin and bind it with glucuronic acid/ sulfate, thus making it conjugated bilirubin. This travels to the duodenum in bile, where, under bacterial action, it is converted to urobilinogen. 90% of the urobilinogen is converted to stercobilinogen (under further bacterial action) and then into stercobilin, which is excreted in faeces. 10% of the urobilinogen is reabsorbed, across the intestinal epithelia. Some of the reabsorbed urobilinogen travels to the kidneys where it is excreted in urine as urobilin (after oxidation). Some of the reabsorbed urobilinogen travels back to the liver via the hepatic portal system

Question 41

ABC transporters

Answer 41

found in liver and elswhere in body. 1. ‘A’TP ‘B’inding ‘C’assette transporter pumps.

2. These are dependent on the hydrolysis of ATP to allow active transport of molecules.
3. Examples include: Bile Salt Export Pump (BSEP)/ Multidrug Resistance Associated Protein 2 (MRP2) – both these are used to secrete primary bile acids fromhepatocytes into the bile canaliculi.

Question 42

alanine transaminase ALT

Answer 42

produced in liver. 1. This is a transaminase enzyme, involved in the transamination process between Glutamine/Glutamate and Pyruvic Acid/Pyruvate to produce α-ketoglutamic acid/α-ketoglutarate acid and alanine

Question 43

asparate transaminase AST

Answer 43

produced in the liver1. This is a transaminase enzyme, involved in the transamination process between Glutamate and Oxaloacetate to produce α-ketoglutarate acid and asparate.

Question 44

alcohol dehydrogenase

Answer 44

priduced in stomach. metabolises alcohol in stomach. females lack it.

Question 45

cytochrome p4502E1

Answer 45

in liver, involved in alcohol metabolism in liver, alcohol converted acetaldehyde and excreted by conversion to CO2 in citric acid cycle

Question 46

cyclin

Answer 46

1. These activate CDKs by binding to them and acting as checkpoints throughout the cell cycle.

Question 47

CDK cyclin dependant kinase

Answer 47

1. These are activated by binding to cyclins.
2. These are enzymes that serve as checkpoints throughout the cell cycle.
3. E.g. cyclinA/CDK4 and cyclinE/CDK2 and cyclinB/CDK1

Question 48

cyclin kinase inhibitor

Answer 48

1. Inhibit CDKs and cause cell cycle to go into arrest.

2. E.g. p21

Question 49

p53

Answer 49

1.In a normal cell cycle, p53 is degraded.
2.In an abnormal cell cycle, p53 is not degraded and it serves to kill the cell and prevent any abnormal tissue growing, by:
Inducing apoptosis
Causing cell cycle arrest by promoting p21 (CKI)
Blocking angiogenesis
Promoting DNA repair
3.P53 is a tumour suppressor gene protein. If both alleles of the gene that encodes p53 are mutated, then p53 can no longer induce DNA repair and apoptosis, thus the continuation of an abnormal cell cycle occurs.