Metabolism 8 Flashcards
Where is cholesterol found? In what form?
What is cholesterol a precursor for (2 things) Where are these made?
Cholesterol is found as a component of cell membranes.
It is also found in its storage form, cholesterol ester.
Cholesterol is a precursor of bile acids, which are made in the liver, and a precursor
of steroid hormones, which are made in endocrine tissues
p 3
(bile acids-glycoholate)
(steroid hormones- progesterone, 17 beta-estradiol, testosterone, dehydroepiandrosterone, cortisol, aldosterone, 1,25-dihydroxy-vitamin D3)
In the intestines what happens to cholesterol obtained from diet?
Cholesterol (C) and cholesterol esters (CE) can be obtained from the diet (animal sources).
In the intestines, it is packaged into chylomicrons along with TAG’s.
flow chart p 4
Cholesterol can be synthesized in the body. Describe this process and how it will be transported.
Cholesterol can be synthesized in the body. In the liver, it is packaged into
VLDL’s (very low density lipoproteins) along with TAGs.
p 4
What is mevalonate?
Its formation is catalyzed by what enzyme?
Mevalonate, an important intermediate in cholesterol biosynthesis,
is formed in a reaction that is catalyzed by the rate-limiting enzyme,
HMG-CoA reductase.
HMG-CoA reductase catalyzes the rate limiting step in cholesterol biosynthesis,
conversion of HMG-CoA to mevalonate.
Draw for formation of cholesterol.
p 5
acetoacetyl CoA combines with Acetyl CoA and water to form HMG CoA
HMG-CoA + 2NADPH +2 H+ leads to mevalonate +CoA +2NADP+
HMG-CoA reductase catalyzes the rate limiting step in cholesterol biosynthesis,
conversion of HMG-CoA to mevalonate.
Describe the molecules whose concentration will regulate the activity of HMG-CoA reductase.
The activity of HMG-CoA reductase is regulated by the concentration of mevalonate, cholesterol, AMP, and sterols.
How does HMG-CoA Reductase mRNA Production regulate HMG-CoA reductase activity?
Sterols (e.g., cholesterol) bind to SRE (steroid regulatory elements) and inhibit mRNA
production, leading to decreased synthesis of the enzyme, and decreased synthesis of
cholesterol.
Describe regulation of HMG-CoA Reductase mRNA Translation:
Translation is inhibited by nonsterol metabolites derived from mevalonate.
Describe regulation of HMG-CoA Reductase Enzyme Degradation:
A high level of the products, cholesterol and mevalonate, leads to rapid degradation of
the HMG-CoA reductase enzyme.
Describe regulation of 4. HMG-CoA Reductase Phosphorylation:
HMG-CoA reductase is phosphorylated and inhibited by an AMP-activated protein
kinase; cholesterol synthesis ceases when ATP is low.
Slide 19
Bile acids (salts) are formed in the liver from cholesterol. What is the rate limiting enzyme?
The rate-limiting enzyme in bile acid biosynthesis is 7-alpha-hydroxylase.
Diagram p 9/slide 20
cholesterol to free bile acid…conjugated bile salt
Draw a flow chart of cholesterol synthesis and utilization.
p 10
Cholesterol excess leads to what following changes in enzyme activity, what are the implications?
Increase/decrease in HMG-CoA reductase? ACAT? 7-alpha-hydroxylase?
- decrease HMG-CoA reductase (decreased cholesterol synthesis)
- increase ACAT (increased cholesterol storage/utilization)
- increase 7-alpha-hydroxylase (increased bile acid synthesis/utilization)
Cholesterol deprivation leads to what following changes in enzyme activity, what are the implications?
Increase/decrease in HMG-CoA reductase? ACAT? 7-alpha-hydroxylase?
- Increase HMG-CoA reductase (increased cholesterol synthesis)
- Decrease ACT (decreased cholesterol storage/utilization)
- Decrease 7-alpha-hydroxylase (decreased bile acid synthesis/utilization)
Draw complete metabolism of acetyl CoA chart and highlight effects of epinephrine.
Review slide 7
or Slide 27
