Cholestrol Synthesis Flashcards
What is found in excess in the liver in both fasted and fed state?
Acetyl CoA
What is the key enzyme in cholesterol synthesis?
HMG-CoA reductase
What stimulates HMG-CoA reductase?
Insulin
What inhibits HMG-CoA reductase?
AMPK (AMP-activated protein kinase)
What stimulates AMPK?
AMP stimulates it large amounts of ATP breakdown creates AMP
What inhibits AMPK?
Phosphocreatine
What does a deficiency in liver kinase B cause?
Doesn’t uptake glucose leaving it in the bloodstream hyperglycemia
What increases AMPK activity?
Leptin and adiponectin
What does AMPK cause?
Energy producing processes and decreases energy consuming processes
What breaks down HMG-CoA reductase?
Ubiquitin
What inhibits HMG-CoA and why?
Glucagon and epinephrine so you do not waste energy on cholesterol during fight or flight or fasted states
What does Insig do?
Holds SCAP-SREBP complex in ER in presence of sufficient cholesterol concentrations
What occurs to the SCAP-SREBP complex once cholesterol levels decrease?
Insig releases it and it SCAP-SREBP continues to the Golgi
What occurs to Insig once the SCAP-SREBP complex leaves the ER?
It is ubiquinated for proteolysis
Once in the Golgi what occurs to the SCAP-SREBP complex?
SREBP is cleaved from SCAP by MBTPS1
What occurs once SCAP is released from SREBP?
MBTPS2 cleaves it releasing the transcription factor
What does ACAT do and why?
Esterifies cholesterol so that it can be transported and stays out of the membrane
What occurs with a defect in ApoE?
IDL and chylomicrons remain in circulation too long causing hyperlipoproteinemia
What does LCAT add to cholesterol?
Phosphatidylcholine instead of a fatty acid (ACAT fatty acid)
Where does HDL get a fatty acid for esterification?
Its own membrane (no TAGs intracellularly)
What receptor allows for LDL to be taken in by cells?
Apo B
What occurs to LDL once inside the cell?
Transported to lysosomes to breakdown everything and receptor sent up to surface again
What is the transcription of HMG-CoA reductase dependent on?
Intracellular cholesterol concentration
What is the rate limiting step of steroid synthesis?
StAR
What is StAR?
Protein responsible for transport of cholesterol into the mitochondria
What is the first step in synthesis of all steroid hormones?
Cholesterol to progestagens
What do progestagens get turned into?
Mineralocorticoids
Glucocorticoids
Androgens
What do estrogens come from?
Androgens
What enzyme is needed for androgens to turn to estrogens?
Aromatase
Where are progestagens made?
Adrenal cortex, gonads, CNS
Androgens are made:
Adrenal cortex and gonads
Mineralocorticoids/glucocorticoids are made:
Adrenal cortex
Estrogens are made:
Gonads
When and where are estriols made?
Only in pregnancy by fetal adrenal glands, liver and placenta
What is dihydrotestosterone?
5% of test is turned into this has a huge affect on secondary sex characteristics not primary characteristics
What enzyme converts testosterone to dihydrotestosterone?
5 alpha-reductase
What can 5 alpha-reductase deficiency lead to?
Male patterned baldness, benign prostatic hyperplasia, and prostate cancer
What can aromatase deficiency lead to?
In males and females no secondary sex characteristics
