Hardman - Cholesterol Flashcards
Isoprenes
Consist of terpenes and steroid
Plant pigments and odors
5-Carbon initiator Unit in Synthesis of Cholesterol
Prenylation
Attachment of farnesyl or geranylgeranyl group
Act as anchor to membranes
What two molecules begin synthesis of ketons and cholesterol?
Where does this occur?
Acetoacetyl CoA + Acetyl CoA
=
HMG-CoA
Cytoplasm
What is the commited step in cholesterol formation?
Synthesis of mevalonate
What is the rate limiting enzyme in cholesterol formation?
HMG-CoA Reductase
(catlyzes HMG-CoA to Mevalonate)
What is mevalonate converted to?
5-carbon IPP (isopentenyl pyrophosphate)
What is IPP isomerized to?
How many ATP does this require?
IPP isomerized to dimethylallyl pyrophosphate
Requires 3 ATP
How many molecules of IPP are required to form squalene?
What are the intermediates during multiple condensations?
What is total ATP required?
Six IPP’s are condensed to form squalene
Dimethylallyl
I
Geranyl
I
Farnesyl
I
Squalene
18 ATP Total
Start to finish: Cholesterol Synthesis
Acetoacetyl CoA+Acetyl CoA
I
HMG-CoA
***I (HMG-CoA Reductase)***
Mevalonate
I
5-P Mevalonate
I
IPP
I
Dimethylallyl
I
Geranyl
I
Farnesyl
I
Squalene
I
Lanosterol
I
Cholesterol
Ah! Ah! Help Me Plan In Diet Good Food Stay Low in Cholesterol
How is cholesterol synthesis regulated?
HMG-CoA Reductase rate limiting enzyme
Four methods:
- Sterol Dependent
- (excess cholesterol binds SCAP, blocks release of SREBP)
- Sterol Independent
- Phosphorylated HMG CoA Reductase
- Hormonal
- Activate: Insulin
- Inhibit: Glucagon/Epinephrine
- Inhibition by Drugs
- Statins (w/side effects)
What are the major plasma lipoproteins from least dense to most dense?
Least: Chlyomicron
VLDL
IDL
LDL
Most: HDL
Chylomicron
Largest lipoprotein
Dietary fat transport
VLDL
Endogeneous fat transport
IDL
LDL precursor
LDL
Cholesterol transport
HDL
Reverse cholesterol transport
How do the intestines and liver package cholesterol (and fats) to enter the capillaries?
How do extra hepatic tissues transport cholesterol to the liver?
Intestines: Chylomicrons
Liver: VLDL
Extrahepatic: HDL
What apolipoprotein is unique to chyolomicrons?
Where are enzymes for chylomicrons located?
What adds apo E and apo C
B-48
Smooth ER
Circulating HDL
What enzyme hydrolyses TAG to FAs + Glycerol?
What activates?
What removes chylomicron remnants?
Lipoprotein Lipase
Activate: Insulin
Liver clears remnants
What lipoproteins have the most TAG content?
Chylomicron highest TAG % (least dense)
HDL have lowest TAG % (most dense)
What apolipoproteins tag VLDL?
B-100
C-11
What happens to apolipoprotein lipase C and E following degradation?
Returned to HDL
What is tag is recognized for uptake of IDL and LDL?
How many isoforms are there?
What are results of defects in each?
apo E
E2, E3, E4
E3: Familial Hyperlipoproteinemia (high cholesterol), early athersclerosis
E2: Reduce Alzheimers
E4: Increase Alzheimers
Degradation of Cholesterol: Sterol Nucleus
Converted to bile acids
Degradation of Cholesterol: Cholesterol
Secreted into gall bladder
Degradation of Cholesterol: Futher uses?
Synthesis of sterol hormones
What can excess cholesterol lead to in the gall bladder?
gall stones
Excess cholesterol forms what?
Bile acids, bile salts
What is the rate limiting step of steroid synthesis?
Conversion of cholesterol to pregnenolone
What is the order of steroid synthesis?
Cholesterol
I
Pregnenolone
I
Progrestagens
I
- Glucocroticoids
- Mineralcorticoids
- Androgens
What are androgens converted to?
Testosterone and Estradiol
What are estrogens and testosterone vital for?
Reproduction and physical development
What are progestins vital for?
Maintenance of pregnancy
What are two sources of Vitamin D?
What occurs during deficiency?
Sunlight and Supplementation
Children: Ricketts
Adults: Osteoperosis
How does thermogenesis in BAT occur?
Low T activates cascade for thermogenin and UCP-1 to uncouple ETC, releasing heat
What is the rate limiting step of steroid formation?
Cholesterol (C27) to Pregnenolone (C21)
Vitamin D is converted to its active form where?
Kidney (Vit D to Calcitriol)
