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Flashcards in Lipid metabolism Deck (24):
1

three phases of FA synthesis

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)

2

functions of lipids

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

3

lipid soluble vitamins

A, D, E, K

4

what organ does FA synthesis primarily occur in

LIVER

sometimes in adipose tissue, brain, kidneys

5

what is the precursor of FA synthesis

acetyl-CoA (2C)

6

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

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.

7

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

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.

8

What are the regulatory reactions of fatty acid synthesis?

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

9

What are the two phases of fatty acid breakdown?

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

10

long chain fatty acid

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

11

What are the 4 steps of beta oxidation?

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

12

ATP equivalents for energy intermediates

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

13

four types of ACADs

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

14

carnitine shuttle

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

15

rate limiting step of beta oxidation

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

16

each round of beta oxidation removes how many C

2C

17

how do odd number fatty acid chains do it differently?

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

18

Where are peroxisomes used in beta oxidation

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

19

deficiencies in carnitine shuttle

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.

20

peroxisome deficiencies

result in the inability to degrade very long chain FA. IE
Zellweger syndrome, infantile refsum,

21

MCAD deficiency

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.

22

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

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

23

ketone bodies

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

24

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

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).