Exam 4

Question 1

how is most plasma cholesterol found

Answer 1

esterified

*the esterified form is not found in cells or in membranes as much

Question 2

important functions of cholesterol

Answer 2

1. drives formation of lipid micro domains in plasma membrane
2. precursor for steroid hormones and vitamin D
3. stiffens plasma membrane and makes it less permeable, or “regulates permeability”
4. can interact with and affect the structure of integral membrane proteins (including receptors - importantly)

Question 3

where do all of the carbons in cholesterol come from

Answer 3

acetyl-CoA

Question 4

where is the energy required for cholesterol synthesis derived?

Answer 4

1. the hydrolysis of the thioester bonds of acetyl CoA

2. ATP hydrolysis

Question 5

where does synthesis of cholesterol begin and where are the key enzymes

Answer 5

synthesis begins in the cytoplasm, and key enzymes are in the ER membrane

Question 6

characteristics of cholesterol

Answer 6

1. limited flexibility
2. amphipathic
3. can be found in membranes in several orientations (some are more energetically favorable than others)

Question 7

describe the solubility of cholesterol in membranes

Answer 7

less soluble in membranes with more unsaturated fatty acids

*this was tested and characterized in artificial plasma membranes

Question 8

where and how are ketone bodies formed

Answer 8

mitochondrial matrix

• they are formed from acetyl CoA when fat breakdown is the primary catabolic mechanism in metabolism
• HMG-CoA is broken into acetoacetate by HMG-CoA lyase and an acetyl CoA is lost

Question 9

how is HMG-CoA formed in the mitochondria?

Answer 9

1. 2 acetyl CoA units are condensed in a reaction catalyzed by mitochondrial acetoacetyl thiolase (ACAT1)
   - one CoA is lost as part of this reaction
   results in acetoacetyl COA
2. a third acetyl CoA molecule is condensed with the first 2 by mitochondrial HMG-CoA Synthase
   - another CoA is lost and the resulting compound is HMG-CoA
   - HMG-CoA either reduced to 3-hydroxybutyrate or converted to acetone

Question 10

how is HMG-CoA formed in the cytosol?

Answer 10

the mechanism is the same as in mitochondria, except it uses the following enzymes

1. cytoplasmic acetoacetyl thiolase (ACAT2)
2. cytoplasmic HMG-CoA synthase

*remember that the resulting HMG-CoA has 6 carbons

Question 11

what is HMG-CoA used for in the cytoplasm?

Answer 11

HMG-CoA reductase reduces it to form mevalonate

2 reductions occur