Lipid metabolism

Question 1

three phases of FA synthesis

Answer 1

phase 1) cytosolic entry of acetyl CoA (moving acetyl-CoA from mito matrix to cytoplasm for remainder of rxns)
phase 2) generation of malonyl CoA (RATE LIMITING, acetyl-CoA is carboxylated to malonyl-CoA in cytosol.
phase 3) fatty acid chain formation (combines either malonyl-CoA or acetyl-CoA to form longer and longer FA chains)

Question 2

functions of lipids

Answer 2

store fuel more efficiently than glycogen/carb metabolism. structural components of membranes, used in signaling pathways, brown fat generates heat, bile salts (lipid) used to digest fat

Question 3

lipid soluble vitamins

Answer 3

A, D, E, K

Question 4

what organ does FA synthesis primarily occur in

Answer 4

LIVER

sometimes in adipose tissue, brain, kidneys

Question 5

what is the precursor of FA synthesis

Answer 5

acetyl-CoA (2C)

Question 6

how does acetyl-CoA end up in the cytoplasm for FA synthesis?

Answer 6

acetyl-CoA is used in TCA cycle inside mitochondrial matrix. It is added to OAA and condensed to form citrate. Citrate moves into the cytosol via a citrate transporter. Citrate is converted into OAA via ATP citrate lyase which releases acetyl-CoA as a byproduct.

Question 7

what happens to citrate when it gets into the cytosol after leaving TCA cycle?

Answer 7

ATP citrate lyase adds a CoA and a phosphate group from ATP onto citrate to produce OAA and acetyl-CoA. OAA is reduced to malate and further oxidized to pyruvate which is then able to be transported back into the mito matrix where is will regenerate OAA and feed back into TCA cycle.

Question 8

What are the regulatory reactions of fatty acid synthesis?

Answer 8

1) converting citrate into OAA via ATP CITRATE LYASE
2) carboxylating acetyl-CoA into malonyl-CoA via ACETYL-COA CARBOXYLASE (ACC) rate determining step
3) FAS complex (FATTY ACID SYNTHASE) is activated by insulin and a high carb/low fat diet. inhibited by high fat diet and starvation

Question 9

What are the two phases of fatty acid breakdown?

Answer 9

phase 1) transport of free fatty acids from cytosol into mito matrix via carnitine shuttle
phase 2) beta oxidation and ATP generation

Question 10

long chain fatty acid

Answer 10

FA over 20 C long, must use albumin to cross plasma membrane into cell for beta oxidation

Question 11

What are the 4 steps of beta oxidation?

Answer 11

1. oxidation
2. hydration
3. oxidation
4. thiolysis

Question 12

ATP equivalents for energy intermediates

Answer 12

1 mol NADH = 2.5 mol ATP
FADH 2 1.5
GTP 1

Question 13

four types of ACADs

Answer 13

SCAD: short chain fatty acid CoA dehydrogenase
MCAD (~8C)
LCAD(~20C)
VLCAD (20+C)

Question 14

carnitine shuttle

Answer 14

a series of enzymes that move long chain FA from the cytosol into the mitochondrial matrix using the enzymes:

1: fatty acyl CoA synthetase
2: CPT1
3: CACT
4: CPT2

Question 15

rate limiting step of beta oxidation

Answer 15

found within the carnitine shuttle during the second enzymatic reaction when FACoA transfers its fatty acyl group to carnitine via CPT1

Question 16

each round of beta oxidation removes how many C

Answer 16

2C

Question 17

how do odd number fatty acid chains do it differently?

Answer 17

2C units (acetyl CoA) are removed like usual until a 3C (propionyl CoA) remains. This is eventually converted into succinyl CoA which can be used as an intermediate in TCA

Question 18

Where are peroxisomes used in beta oxidation

Answer 18

for very long chain fatty acids, they are degraded in peroxisomes until they become a long FA chain (20C) and then can be transported into the mitochondria via carnitine shuttle for the rest of beta oxidation. No ATP is generated to convert very long chain FA to long chain FA

Question 19

deficiencies in carnitine shuttle

Answer 19

would lead to the inability for long chain fatty acids to enter mitochondria for the rest of beta oxidation to occur. unable to break down fat stores.

Question 20

peroxisome deficiencies

Answer 20

result in the inability to degrade very long chain FA. IE

Zellweger syndrome, infantile refsum,

Question 21

MCAD deficiency

Answer 21

autosomal recessive, resembles carnitine deficiency bc unable to breakdown FA. FA accumulate in liver, liver function is decreased, liver ammonia levels can rise to poisonous levels.

Question 22

In fasting/starving state what happens to beta oxidation (hint:ketones)

Answer 22

excessive beta oxidation leads to an excessive amount of acetyl CoA so that the extra go through a different pathway to produce ketone bodies

Question 23

ketone bodies

Answer 23

are only made in the matrix of mitochondria in the liver, water soluble, and highly acidic (ketoacidosis).

Question 24

what are the two major essential fatty acids and why are they essential?

Answer 24

omega-3 and omega-6 fatty acids. humans can’t synthesize a double bond farther than 9 away from the alpha-end (carboxyl end), but omega-3 and omega-6 are counted from the other end (omega end).