DLA 13-14 + lecture 21-22

Question 1

The rate limiting enzyme of cholesterol synthesis?
occurs where?
what is needed?

Answer 1

HMG CoA reductase

occurs in the cytosol and ER

acetyl CoA, NADPH, and ATP are needed for synthesis

Question 2

synthesis of mevalonate

Answer 2

HMG CoA is reduced to mevalonate

this reaction is done by HMG CoA reductase
requires two NADPH
the regulatory step

inhibited by glucagon and statins
activated by insulin

Question 3

esophageal manometry

Answer 3

measures both quantitative and qualitative measurements of esophageal pressure and peristaltic coordination.

Question 4

typical pressures in the esophagus

Answer 4

UES = +40

mid-esophagus = -5

LES = +20

stomach = +5

Question 5

Achalasia

Answer 5

disorder of the ENS that impacts the smooth muscle of the esophagus

have great difficulty swallowing food
usually aspirate food
suffer malnourishment

Question 6

geranyl groups

Answer 6

used to anchor proteins in the cell membrane

Question 7

farnesyl groups

Answer 7

needed for specific proteins

Question 8

farnesyl-PP

Answer 8

used for CoQ (ETC) and dolichol-PP (used for N-linked)

Question 9

Smith-Lemli-Optiz syndrom (SLOS)

Answer 9

caused by a deficiency in 7-dehydrocholesterol reductase

his enzyme is responsible for the final step of cholesterol synthesis

loss of function mutations in DHCR7 leads to this enzyme deficiency

build up of 7-dehydrocholesterol

auto recessive 
heart defects 
malformations 
microcephaly 
mental disability 

cholesterol administration helps with growth but not CNS defects

Question 10

cholesterol degradation

Answer 10

conversion to bile acids or reduction of the cholesterol by gut bacteria

Question 11

cholesterol gallstone disease (cholelithiasis)

Answer 11

precipitation of cholesterol in the gallbladder due to bile salt deficiency

diagnosis by CT or sonogram

Question 12

Cholestatic disease

Answer 12

biliary obstruction of either the small bile ducts or the larger ducts

bile flow blockage leads to lipid malabsorption with steatorrhea
can also have jaundice due to hyperbilirubinemia

Question 13

causes and treatment of cholelithiasis or cholesterol gallstone disease

Answer 13

cause:
decreased bile production (liver dysfunction)
increased secretion of cholesterol into bile
obstruction
suppression of bile synthesis
blood blockage
malabsorption of bile acids

treatment: 
removal of gallbladder 
give chenodiol 
disintegration of stones 
contact dissolution

Question 14

regulation of cholesterol synthesis (basic)

Answer 14

high dietary cholesterol = low synthesis

low dietary intake = high synthesis

Question 15

HMG-CoA regulation of cholesterol synthesis

Answer 15

phosphorylation by cAMP kinases will inactivate the reductase or reductase will be degraded

gene expression is controlled by cholesterol levels

reductase is activated by substrate availability

insulin activates reductase

glucagon and statin = inhibit

Question 16

SREBP protein

Answer 16

low cholesterol stimulates the release of this regulatory protein from the ER

results in increased transcription of the reductase gene

increase amount of HMG-CoA reductase

Question 17

uqibuitin system in proteosomes

Answer 17

degradation of HMG CoA reductase is controlled by this pathway

Question 18

AMPK and cholesterol

Answer 18

high intracellular concentrations of AMP stimulate AMPK

this enzyme will phosphorylate HMG CoA reductase and inactive it

can be dephosphorylated by a phosphoprotein phosphatase (activated by insulin) and activate the kinase

Question 19

statin drugs

Answer 19

structural analog of HMG CoA

statin drugs are reversible competitive inhibitors of HMG CoA reductase

prevent synthesis of cholesterol

Question 20

ACAT

Answer 20

the conversion of intracellular cholesterol to cholesterol esters

Question 21

parasympathetic regulation of GI motility

Answer 21

ACh

increase the rate of generation of action potentials, leading to more contractions and motility

Question 22

VIP and NO regulation on GI motility

Answer 22

decreased rate of generation of action potentials,

causing decreased contraction and motility

Question 23

Two main GIT motility states

Answer 23

fasting state: Migrating motor complex
cleans the stomach and gut during fasting

fed state: segmentation and peristalsis
aids in mixing and moving food

Question 24

characteristics of the migrating motor complex

function? neural? cause?

Answer 24

pattern of activity during fasting
strong contractions every 90 min

function:
prevent bacterial overgrowth
movement of undigested material

neural:
generated by ENS

motilin induces the MMC
stop after ingestion of a meal

Question 25

interstitial cells of cajal

Answer 25

pacemaker for the SM in the gut
drive basic electrical rhythm

not action potentials

generate slow waves

Question 26

swallowing reflex

Answer 26

coordinated by cranial nerve 9 and 10 via the medulla

nucleus ambiguus: somatic nerves - regulate pharynx and striated areas of esophagus

dorsal motor nucleus: autonomic nerves- control SM of esophagus