Fatty acids and ketones 11 Flashcards
What does insulin promote in adipocytes: fat uptake or glucose uptake?
both !
How is the glycerol backbone generated to synthesize TGs?
via glycolysis - G3P
Acyl transferases catalyze the transfer of acyl groups from what substrates to G3P?
fatty acyl-coA
Hormone sensitive lipase releases FA preferentially from what?
DG and MG (releases FA more slowly from TG)
What activates HSL?
catecholamines and glucagon
cAMP dependent protein kinase phosphorylates HSL so that it is more active
What inhibits lipolysis?
NEFAs (via product inhibition) and insulin (via phosphatase)
What lipase catalyzes the rate limiting step in lipolysis?
adipose triglyceride lipase
- formation of DG from TG
What happens in mice if these enzymes are deficient:
- HSL
- Adipose triglyceride lipase
- not obese
- obese
- –indicates its the rate limiting step
What are peripillins?
proteins that coat the surface of peripheral lipid droplets
-prevent access of lipases
What disrupts the perilipin sheet, allowing lipase access?
phosphorylation by cAMP dependent kinase
What step is the key regulation event in lipolysis?
phosphorylation of perilipins
What is lipotransin?
protein on the droplet surface that helps HSL dock
How are NEFAs transported in the blood?
bound to albumin ALWAYYYYYS
What transporter does glycerol use to leave the cell?
AQPad
Describe the delta system
Total C: double bond: delta: positions of first C in each double bond
Describe the omega system
Total carbons: number of double bond: omega: first C from the methyl side
True or false: all members can be synthesized from the parent member
true
True or false: A FA of one class can easily be converted to another by humans
FALSEEE
What is the omega formula for Plamitoleic acid?
16:1ω-7
What is the omega formula for oleic acid?
18:1ω-9
What is the omega formula for linoleic acid?
18:2ω-6
What is the omega formula for linolenic acid?
18: 3 ω-3
Which fatty acids of this list are essential: oleic, linoleic, linolenic, palmitic?
linoleic and linolenic
Can beta oxidation occur with short and medium fatty acids?
yes!
What enzyme is involved in activating fatty acids to fatty acyl-coA?
thiokinase
If the Overall ΔG°’ for activating fatty acids is near 0, what drives the reaction?
pyrophosphatase
How many ATPs are used to activate a fatty acid for B-oxidation?
2
What enzyme in the outer mitochondrial membrane, catalyzes the transfer of a LCFA from coA to carnitine?
CPT1
The carnitine acylcarnitine transporter transports what two molecules which ways? where is this located?
inner mito membrane
acylcarnitine into mitochondria
carnitine out of mitochondria
Acyl coA is regenerated by what enzyme on the inner mitochondrial membrane?
CPTII
What three other pathways besides beta oxidation exist to oxidize FA?
- B ox of LCFAs and polyunsat FA in peroxisomes
- alpha-ox of branched chain FAs in mito
- omega-ox in ER
What is CTP1 inhibited by?
malonyl coA
-first product of committed step in FA synthesis
What is the first step of beta oxidation?
oxidize the alpha-B bond to a double bond
dehyrogenation by acyl-coA dehydrogenase
e- from FADH2 are passed down e- chain
acyl coA –> trans enoyl coA
What is the second step of beta oxidation?
hydration across the alpha-B double bond
-2,3 enoyl -coA hydrase
trans enoyl coA ->B hydroxyacyl-coA
Whats the third step of beta oxidation?
dehydrogenation
3- hydroxyacyl coA dehydrogenase
B-hydroxyacyl coA –> B -Ketoacyl coA
What is the fourth step in beta oxidation?
thiolysis
thiolase
B-ketoacyl CoA –> acyl coA 2 C shortened + acetyl coA
What steps involve a trifunctional protein?
2, 3, 4
How many FADH and NADHs are produced in each round of beta oxidation?
one each
How many ATP is produced by one FADH?
two ATP
How many ATP is produced by one NADH?
three ATP
What is the net gain of ATP in beta oxidation?
129 ATP per 16 Carbons –> 8 ATP/C
What percent of free energy is converted to heat , what percent to ATP in beta oxidation?
60% heat
40% ATP
How many ATP/C are produced in glycolysis?
36 ATP per 6C –> 6ATP/C
If a beta gamma double bond is present, what is the cost?
1 FADH2 –> 2 ATP
If a delta 4 double bond is present, what is the cost?
1 NADPH –> 3 ATP
Linoleic acid E will be reduced by how many ATP compared to stearic acid?
5 ATP
Where and when are ketone bodies produced?
liver mitochondria during fasting and starvation
overproduced in type 1 Diabetes
Are ketone bodies used as fuel in the liver?
NOOO
Which ketone bodies can be used as fuel by many tissues including the brain?
acetoacetate, B-hydroxybutyrate
What ketone body is a metabolic dead end?
acetone
What do high levels of acetyl coA do?
inhibits pyruvate dehydrogenase
activates pyruvate carboxylase
-OAA increases and diverted to glycolysis
What is the effect of high levels of NADH in mitochondria from B-oxidation?
inhibits isocitrate dehydrogenase
-citrate accumulates
- OAA is converted to malate
- malate leaves the mito and used for gluconeogenesis
What happens to the excess acetyl coA from B-oxidation?
used for making ketone bodies
-does not enter the TCA cycle
When are high levels of acetyl coA encountered?
during fasting, heavy alcohol, high fat/low carb diets, diabetes
In ketone metabolism:
acetyl coA + acetyl coA –> acetoacetyl coA
what enzyme?
what type of reaction?
B-ketothiolase
condensation reaction
In ketone metabolism:
acetoacetyl coA + acetoacetyl coa –> HMG coA
what enzyme?
what type of reaction?
HMG COA synthetase
condensation
HMG - COA –> acetyl coA + acetoacetate
what enzyme?
HMG-coA lyase
What two products are formed from acetoacetate?
acetone and b-hydroxybutyrate
Why cant extra-hepatic tissues synthesize KBs?
lack high levels of HMG-coA synthetase
lack HMG coA lyase
What happens in ketoacidosis?
more KBs are produced than the extrahepatic tissues can burn and more than kidneys can excrete
lots of glucagon , no insulin
Can ketoacidosis happen in type 2 diabetes?
nopeeeeee
theres still insulin present
