Overview of Lipid Biochemistry

Question 1

What is different about fat metabolism vs. carbohydrate?

Answer 1

• Talking about more than 1 type of molecule (which flavor of fat do we have?)
• Lipids are hydrophobic (causes problems with transit in blood and cells)

Question 2

Structure of stearate

Answer 2

C-18 saturated fat

• COOH with 18 C’s
• Saturated = no double bonds
• Crystallize at room temperature; doesn’t move around well in blood or adipose

Question 3

Oleic acid

Answer 3

C-18, mono-unsaturated fat

• n6 location of double bond
• occurs in cis configuration, flows better

Question 4

5 classes of fatty molecules

Answer 4

1. FA
2. Phospholipids
3. Cholesterol
4. Cholesterol Esters
5. Triglycerides

Question 5

Fats in order of most nonpolar to polar

Answer 5

1. TG
2. Cholesterol esters
3. Cholesterol (amphipathic)
4. Phospholipids (amphipathic)
5. FA

Question 6

Amphipathic

Answer 6

• means it has both a polar and a nonpolar component

Question 7

Triglyceride structure

Answer 7

1. Glycerol backbone

2. 3 FA (coming from diet) esterified to backbone

Question 8

Phospholipid

Answer 8

Polar headgroup, nonpolar tail

1. PO4 attached to R group (like choline, inositol, etc.)
2. Glycerol backbone
3. 2 FA

Question 9

Cholesterol

Answer 9

1. Alcohol - has some charge
2. Ring structure

Free cholesterol lives in membranes because it is amphipathic
If you turn it into an ester (add FA) you remove the charge that it had, and it becomes very nonpolar.

Question 10

If you get a backup of TCA cycle, where does G6P go?

Answer 10

It can be converted to glycerol which then combines with FA –> TGs

Question 11

De novo lipogenesis pathway

Answer 11

A way to take Acetyl-CoA into fatty acids

Acetyl-CoA –> Citrate –(ACA carboxylase)-> malonyl CoA —(Fatty acid synthase)-> Fatty acids –> TG

and in reverse:
FA –> Fatty acyl CoA –(Fatty acid carboxylase)-> Acetyl-CoA

Question 12

What enzyme breaks down TG to FA?

Answer 12

Hormone sensitive lipase (in the setting of increased glucagon and decreased insulin)

Question 13

2 key steps for FA to get into mitochondria and end up at acetyl-CoA

Answer 13

1. CPT-1 (carnitine palmitoyltransferase to come to the liver and into the mitochondria)
2. Beta-oxidation

Acetyl-CoA will build up, this shuts off the TCA, which allows pyruvate to go to OAA and then gluconeogenesis. Fat gives both stimulus and energy for gluconeogenesis.

Get coordinate regulation via malonyl-CoA (it inhibits the FA entry into mitochondria)

Question 14

Ketogenesis

Answer 14

1. Glucagon has been high for days, insulin is about 0
2. Have tons of breakdown of FA for acetyl-CoA (excessive)
3. Can turn this into ketones in the mitochondria –> ketones go to peripheral tissues as an alternative fuel.

Question 15

Role of cholesterol

Answer 15

1. Cell membranes
2. Hormones
3. Formation of atherosclerotic plaques

Question 16

Cholesterol synthesis

Answer 16

Acetyl-CoA –(HMG reductase)–> cholesterol –> fxns

Question 17

Other lipids

Answer 17

1. Membrane lipid signaling
2. Phospholipid - glycerol
3. Ceramide (made from AA, not glycerol)
4. Glycolipids

These lead to lysosomal storage disorders

Question 18

2 reasons for increased concentration of a substrate within a tissue?

Answer 18

1. Increased production

2. Decreased clearance