Lipid Metabolism Flashcards
(38 cards)
What synthesizes Acetyl-CoA and what is the main importance of Acetyl-CoA?
What is produced?
Glucose, fatty acids and amino acids
Importance is that it brings the metabolic pathways together
ATP and Water is produced
What is the committing step created from Acetyl-CoA that is needed for fatty acid synthesis?
What is the process?
Acetyl-CoA in the presences of Biotin (vitamin B7) and Acetyl-CoA carboxylase creates Malonyl-CoA
Malonyl-CoA is the committing step needed for fatty acid synthesis
How does allosteric (cooperatively) modification effect Citrate (metabolite found in Citric Acid Cycle)?
Stimulate Acetyl-CoA carboxylase leading to high-activity polymer
What is the final product of fatty acid synthesis and what does it do when there are increased levels of lipids?
Palmitoyl-CoA (fatty acid)
Inhibits Acetyl-CoA carboxylase leading to low-activity monomer
This is called Negative Feedback Inhibition
During covalent modification, how does insulin effect fatty acid synthesis?
Insulin increases when excess sugar needs storage.
It causes dephosphorylation (presence of phosphatase enzyme) which activates Acetyl-CoA Carboxylase (increases production of malonyl-CoA ==> fatty acid synthesis)
During covalent modification, how does Epinephrine and Glucagon effect fatty acid synthesis?
These hormones are released and increased when energy is needed
Causes phosphorylation (adding phosphate group) in the presence of protein kinase enzyme which turns off Acetyl-CoA Carboxylase (turns off Fatty Acid Synthesis)
Important enzyme in fatty acid synthesis needed after the committing step production of Malonyl-CoA?
Fatty Acid Synthase
For fatty acid synthesis with even number of Carbon atoms, what does it start with and where does it end?
Acetyl-CoA (start)
Melonyl-CoA (finish)
For fatty acid synthesis with production of an odd number of carbon atoms, what is the intermediate that is needed?
What is the end product?
Propionyl-CoA is the intermediate
Malonyl-CoA or its derivative is the end product and still the committing step for fatty acid synthesis (doesn’t matter if you have a fatty acid with even or odd number)
How is the fatty acid synthase enzyme regulated?
Positively regulated by increased sugar levels and negatively regulated by decrease in fatty acid/fat levels in diet
What is fatty acid elongase and desaturase?
Elongase - increase length of fatty acid hydrocarbon chain
Desaturase- remove desaturation by adding double bond
What are the two major organs for lipid synthesis?
Liver and adipose tissue
BLUF of fatty acid degradation (or fatty B-Oxidation)
**be able to identify on exam
Start with specific fatty acid and end up with a FA with less hydrocarbon chains
For example, you start with 4 Carbon atoms and end up with 2 Carbon atoms
Where does the fatty acid degradation start and end (specific locations)
Starts in the cytoplasm where fatty acyl-CoA forms and ends in the mitochondria where Beta oxidation occurs
These fatty acids can cross the mitochondrial membrane without assistance during fatty acid degradation
Fatty acids with less than 12 carbons
These fatty acids need assistance and are transported into the inner mitochondria matrix
What protein is involved in the process and type of fatty acid?
Fatty acids with 12 or MORE Carbons
Carnitine (protein) that is involved in the process
Explain Fatty Acyl-CoA Transport
Free fatty acid produces the active form of Acyl-CoA from ATP + CoA (catalyzed with Acyl-CoA synthase)
Acyl-CoA can now cross from the cytoplasm into the inner mitochondria space
Acyl-Coa binds with CARNITINE to produce Acylcarnitine which is transferred by carnitine acylcarnitine translocase to the mitochondrial matrix
Once Acylcarntitine is inside the mitochondrial matrix, Beta oxidation can now take place
Signs, symptoms and characteristics of CPT I deficiency
Autosomal recessive in infants and early childhood
Causes decrease in sugar and ketone levels and increase in ammonia when fasting for sick
Damaged/enlarged livers (buildup of fatty acids), kidney problems, muscle breakdown, seizures, coma, and impaired growth
Death is common unless diet of only medium-chain triglycerides
Signs, symptoms and characteristics of CPT II deficiency
Inherited disorder of mitochondrial long-chain FA oxidation
Causes decrease sugar and ketone levels, liver failure, heart damage, fatigue, seizures and early death
Milder form: breakdown of muscle during exercise and fasting with reddish-brown urine
TxT: high-carb/low-fat diet, limit exercise
Beta-Oxidation Steps (4)
- Acyl-CoA dehydrogenase forms double bond between two end carbons
- Enoyl-CoA hydratase hydrates the double bond with hydrogen and hydroxyl
- Hydroxyl is oxidized to a ketone by L-3-hydroxyacyl-CoA-dehydrogenase making a NADH
- Thiolase cleaves 3-keto acyl-CoA to make Acyl-CoA and Acetyl-CoA
End result is CO2 + H2O, 12 ATP and Acetyl-CoA enters citric acid cycle
What are the three enzymes that finalize fatty acid degradation?
3-ketoacyl-CoA thilase, 3-Hydroxyacyl-CoA dehydrogenase, 2,3 Enoyl-CoA hydrase
All three enzymes need to be working properly. If one of the enzymes are not working properly, then it can lead to disease
What are the deficiencies in 2nd Enzyme (dehydrogenase) now working properly?
body can’t convert FA to energy and build up in tissues
Pregnant woman may have liver disease and HELLP syndrome (Hemolysis, elevated liver enzymes and low platelets)
later in life: poor muscle tone and weakness, increase breakdown of muscles and problems with nerves in the arms and legs
What two enzymes deal with beta oxidation of double bonds?
Enoyl-CoA isomerase converts the cis 3-4 double bond to a trans 2-3 double bond (creates an isomer by changing the position of the double bond)
2,4,-Dienoyl reductase reduces it to trans enoyl-CoA enabling beta oxidation to continue (removes a double bond)
What is the products and ATP produced from fatty acid degradation of Palmitate (16 Carbons)?
8 Actyl-CoA + 8 FADH2 + 8 NADH + H+
(96ATP) (16 ATP) (24 ATP)
ATP Theoretical yield = 136 ATP (actual would be a little less)
