Test 2: Lipid and FA Metabolism Flashcards
Where are most FA synthesized?
Liver
What are the fates of fats/lipids/FA’s
energy substrates
precursors
structural elements (membranes etc…)
signaling molecules (cholesterols, leukotrienes, prostaglandins)
Describe the process of absorbing/transporting dietary lipids
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
How are FAs transported?
Free FAs: carried by serum albumin
Lipoproteins: carry TG and cholesterol
What is a lipoprotein composed of?
phospholipid, cholesterol, and protein membrane-bound vesicles containing TGs
What are the four classes of lipoproteins
Chylomicrons
VLDL (very low density lipoprotein
LDL (low density lipoprotein)
HDL (high density lipoprotein)
What lipoprotein has the highest amount of protein?
HDL
What lipoprotein has the highest amount of phospholipid?
HDL
What lipoprotein has the highest amount of cholesterol?
LDL
What lipoprotein has the highest amount of cholesterol ester?
LDL
What lipoprotein has the highest amount of TG?
Chylomicron
What lipoprotein has the lowest amount of TG?
HDL
What forms when foam cells die?
They form atherosclerotic plaques
What lipoprotein do we want in high concentrations and why?
HDL’s
because they scavenge excess cholesterol and prevent foam cells from forming
Very generally, what are common functions of LDL and HDL?
transport cholesterol
Generally, what does VLDL transport and to where?
FAs to target tissues
What happens during starvation to glucagon levels and how does that affect FA
increase level of glucagon in bloodstream
mobilize FAs
describe the glucagon receptor pathway when glucagon binds its receptor/ how FAs are released into the bloodstream
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
What are the components of TG?
3 FAs and 1 glycerol
What are the fates of the components of TG in lipid catabolism?
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..)
About how many ATP are generated per TG? per FA?
~324 (+ ATP from 1 glycerol)
~108 ATP
What carbon gets oxidized in beta oxidation?
B-carbon gets oxidized
What enzyme initiates beta oxidation and is the rate limiting step???
acyl-CoA dehydrogenase
how many acetyl-CoAs will a 16-carbon chain create in B-oxidation?
8 acetyl-CoA’s (2 per carbon)
soooo 24 acetyl-CoA’s per TG
Where does acetyl-CoA go?
can be shuttled to citric acid cycle for gluconeogenesis for energy
Where does acetyl-CoA go during starvation?
can be used to form ketone bodies and shuttled to the blood to be used as energy
What are the ultimate ketone body products?
acetoacetate
acetone
D-B-Hydroxybutyrate
What are ketones converted to in the tissues (brain and myocytes) in starvation?
they are converted to acetyl-CoA to be used as energy
Excess acetyl-Coa can form FAs. What FAs come from acetyl-CoA?
Malonyl-CoA + Acetyl-CoA –> palmitoyl-CoA
What are the stages of FA synthesis?
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
What creates acetyl-CoA?
Pyruvate –pyruvate dehydrogenase–> acetyl-CoA
What is the problem with acetyl-CoA and lipid synthesis in terms of location?
Acetyl-CoA is produced in the M.T. Matrix but lipid synthesis occurs in the cytoplasmic space
Describe the basics of the Citrate Shuttle
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
What are the 3 major components of acetyl-CoA carboxylase (ACC)
Biotin carboxylase
Transcarboxylase
Biotin carrier protein
What is special about FAS II (in bacteria and plants) compared to FAS I (humans and fungi)
FAS II can create up to 20-carbon chain FAs where FASI can only create 16-carbon saturated fats
What initiates acyl chain formation in lipid synthesis?
Fatty Acid Synthase (FAS)
How many NADPH are require per step of adding a malonyl-CoA?
2 NADPH
What two sources provide NADPH to be an anabolic electron donor in Lipid synthesis?
Malic enzyme (shuttling of acetyl-CoA into cytosol)
Pentose phosphate pathway
What is the role of acetyl-CoA in lipid synthesis?
.
What is the role of malonyl-CoA in lipid synthesis?
.
What does Acetyl-CoA Carboxylase produce?
Malonyl-CoA
What is ACC regulated by?
Insulin and glucagon/
high blood glucose and low blood glucose
How does malonyl-CoA regulate things?
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
What is the downfall to foam cells in terms of cholesterol uptake?
They don’t have a mechanism to stop themselves from taking up xs cholesterol which will lead to plaque formation
Normal foam cells take up cholesterol and are moved to the liver to be metabolized (no problems
.
What converts acetyl-CoA to malonyl-CoA?
Biotin
Both LDL and HDL generally transport lipids to the liver. Lipoproteins contain various proportions of cholesterol, TGs, bile salts, and phospholipids.
The first statement is true, the second is false
What are the roles of apolipoproteins?
They are proteins integrated into outer micelle layer of lipoproteins
Lead to breakdown of LP
Activate lipases
Regulate when lipoproteins release FAs
Where does B-oxidation occur?
In MT
What does B-oxidation produce?
Acetyl-CoA
NADH
FADH2
What are the 2 enzymes in FA synthase?
FAS I (makes long C-chains from ….info at 1 hr 42 min)
ACC (acetyl-CoA Carboxylase) which makes malonyl-CoA from acetyl-CoA