Test 2: Lipid and FA Metabolism

Question 1

Where are most FA synthesized?

Answer 1

Liver

Question 2

What are the fates of fats/lipids/FA’s

Answer 2

energy substrates

precursors

structural elements (membranes etc…)

signaling molecules (cholesterols, leukotrienes, prostaglandins)

Question 3

Describe the process of absorbing/transporting dietary lipids

Answer 3

bile salts emulsify the fat in small intestine to form micelles

intestinal lipases degrade TG (triacylglycerol)

FAs and other products taken up by intestinal mucosa and converted into TG

TG packed with cholesterol and apolipoproteins into chylomicrons

chylomicrons move through lymphatic and bloodstream to tissues

Lipoprotein lipases (activated by apoC-II) converts TG to FA and glycerol)

FA enters cells

FAs are oxidized as fuel or reesterified for storage

Question 4

How are FAs transported?

Answer 4

Free FAs: carried by serum albumin

Lipoproteins: carry TG and cholesterol

Question 5

What is a lipoprotein composed of?

Answer 5

phospholipid, cholesterol, and protein membrane-bound vesicles containing TGs

Question 6

What are the four classes of lipoproteins

Answer 6

Chylomicrons

VLDL (very low density lipoprotein

LDL (low density lipoprotein)

HDL (high density lipoprotein)

Question 7

What lipoprotein has the highest amount of protein?

Answer 7

HDL

Question 8

What lipoprotein has the highest amount of phospholipid?

Answer 8

HDL

Question 9

What lipoprotein has the highest amount of cholesterol?

Answer 9

LDL

Question 10

What lipoprotein has the highest amount of cholesterol ester?

Answer 10

LDL

Question 11

What lipoprotein has the highest amount of TG?

Answer 11

Chylomicron

Question 12

What lipoprotein has the lowest amount of TG?

Answer 12

HDL

Question 13

What forms when foam cells die?

Answer 13

They form atherosclerotic plaques

Question 14

What lipoprotein do we want in high concentrations and why?

Answer 14

HDL’s

because they scavenge excess cholesterol and prevent foam cells from forming

Question 15

Very generally, what are common functions of LDL and HDL?

Answer 15

transport cholesterol

Question 16

Generally, what does VLDL transport and to where?

Answer 16

FAs to target tissues

Question 17

What happens during starvation to glucagon levels and how does that affect FA

Answer 17

increase level of glucagon in bloodstream

mobilize FAs

Question 18

describe the glucagon receptor pathway when glucagon binds its receptor/ how FAs are released into the bloodstream

Answer 18

Glucagon binds its receptor –> activates Adenylyl cyclase –> cyclic AMP –> activates Protein Kinase A (PKA) –> activates Hormone Sensitive Lipase (HSL) –> eventually releases FAs from the lipid droplet into the bloodstream

Question 19

What are the components of TG?

Answer 19

3 FAs and 1 glycerol

Question 20

What are the fates of the components of TG in lipid catabolism?

Answer 20

lipase breaks TG into glycerol and 3 FAs

glycerol is shuttled to glycolysis and generates ~5% of energy from lipid catabolism

3 FAs form acyl-CoA which is transported into M.T. (mitochondria) for oxidation via acyl-carnitine transporter (~95% of energy produced from lipid cat..)

Question 21

About how many ATP are generated per TG? per FA?

Answer 21

~324 (+ ATP from 1 glycerol)

~108 ATP

Question 22

What carbon gets oxidized in beta oxidation?

Answer 22

B-carbon gets oxidized

Question 23

What enzyme initiates beta oxidation and is the rate limiting step???

Answer 23

acyl-CoA dehydrogenase

Question 24

how many acetyl-CoAs will a 16-carbon chain create in B-oxidation?

Answer 24

8 acetyl-CoA’s (2 per carbon)

soooo 24 acetyl-CoA’s per TG

Question 25

Where does acetyl-CoA go?

Answer 25

can be shuttled to citric acid cycle for gluconeogenesis for energy

Question 26

Where does acetyl-CoA go during starvation?

Answer 26

can be used to form ketone bodies and shuttled to the blood to be used as energy

Question 27

What are the ultimate ketone body products?

Answer 27

acetoacetate acetone D-B-Hydroxybutyrate

Question 28

What are ketones converted to in the tissues (brain and myocytes) in starvation?

Answer 28

they are converted to acetyl-CoA to be used as energy

Question 29

Excess acetyl-Coa can form FAs. What FAs come from acetyl-CoA?

Answer 29

Malonyl-CoA + Acetyl-CoA --> palmitoyl-CoA

Question 30

What are the stages of FA synthesis?

Answer 30

Transport of acetyl-CoA to the cytoplasm Carboxylation of acetyl-CoA into Malonyl-CoA FA synthase combines acetyl-CoA and malonyl-CoA to start an acyl chain FA synthase adds malonyl-CoA carbons to create palmitate FAs modified in the ER

Question 31

What creates acetyl-CoA?

Answer 31

Pyruvate --pyruvate dehydrogenase--> acetyl-CoA

Question 32

What is the problem with acetyl-CoA and lipid synthesis in terms of location?

Answer 32

Acetyl-CoA is produced in the M.T. Matrix but lipid synthesis occurs in the cytoplasmic space

Question 33

Describe the basics of the Citrate Shuttle

Answer 33

Oxaloacetate in MT matrix converted to citrate Citrate shuttle out to cytoplasm Citrate converted back to oxaloacetate which gives off acetyl-CoA as a product for FA synthesis

Question 34

What are the 3 major components of acetyl-CoA carboxylase (ACC)

Answer 34

Biotin carboxylase Transcarboxylase Biotin carrier protein

Question 35

What is special about FAS II (in bacteria and plants) compared to FAS I (humans and fungi)

Answer 35

FAS II can create up to 20-carbon chain FAs where FASI can only create 16-carbon saturated fats

Question 36

What initiates acyl chain formation in lipid synthesis?

Answer 36

Fatty Acid Synthase (FAS)

Question 37

How many NADPH are require per step of adding a malonyl-CoA?

Answer 37

2 NADPH

Question 38

What two sources provide NADPH to be an anabolic electron donor in Lipid synthesis?

Answer 38

Malic enzyme (shuttling of acetyl-CoA into cytosol) Pentose phosphate pathway

Question 39

What is the role of acetyl-CoA in lipid synthesis?

Answer 39

.

Question 40

What is the role of malonyl-CoA in lipid synthesis?

Answer 40

.

Question 41

What does Acetyl-CoA Carboxylase produce?

Answer 41

Malonyl-CoA

Question 42

What is ACC regulated by?

Answer 42

Insulin and glucagon/ high blood glucose and low blood glucose

Question 43

How does malonyl-CoA regulate things?

Answer 43

It will go back and inhibit B-oxidation In the absence of synthesis, oxidation occurs Malonyl-CoA will go back and inhibit B-oxidation by inhibiting carnitine acyl-transferase I

Question 44

What is the downfall to foam cells in terms of cholesterol uptake?

Answer 44

They don't have a mechanism to stop themselves from taking up xs cholesterol which will lead to plaque formation

Question 45

Normal foam cells take up cholesterol and are moved to the liver to be metabolized (no problems

Answer 45

.

Question 46

What converts acetyl-CoA to malonyl-CoA?

Answer 46

Biotin

Question 47

Both LDL and HDL generally transport lipids to the liver. Lipoproteins contain various proportions of cholesterol, TGs, bile salts, and phospholipids.

Answer 47

The first statement is true, the second is false

Question 48

What are the roles of apolipoproteins?

Answer 48

They are proteins integrated into outer micelle layer of lipoproteins Lead to breakdown of LP Activate lipases Regulate when lipoproteins release FAs

Question 49

Where does B-oxidation occur?

Answer 49

In MT

Question 50

What does B-oxidation produce?

Answer 50

Acetyl-CoA NADH FADH2

Question 51

What are the 2 enzymes in FA synthase?

Answer 51

FAS I (makes long C-chains from ....info at 1 hr 42 min) ACC (acetyl-CoA Carboxylase) which makes malonyl-CoA from acetyl-CoA