Goal 8: TAG Synthesis Flashcards
Only what can you get triacyglycerol from?
- Glucose!
- not from insulin
In TAG synthesis, what pathway gives NADPH, which is needed to turn acetyl CoA to Fatty acids?
Pentode P Pathway (HMP shunt)
What are the main sites of TAG synthesis?
- MAINLY Liver and lactating mammary glands
- partially in adipose tissue
What is the precursor required for TAG synthesis? What is required for the precursor to even be created?
- precursor: acetyl CoA needed for TAG synthesis
- glucose needed to make acetyl CoA
Where is Acetyl CoA produced?
Mitochondria
Where does fatty acid biosynthesis happen?
- In cytosol
- DONT confuse with elongation of fatty acids which happen in smooth ER
Acetyl CoA can’t go from mitchochondria to cytosol without what?
- Converting into citrate to go through citrate shuttle to mitochondria
- once it gets to cytosol, citrate is turned back to Acetyl CoA
What enzyme turns NADP to NADPH? Where does it happen?
- malic enzyme
- cytosol
What is the first step of fatty acid biosynthesis? What regulatory enzyme makes this happen? What coenzymes are required to make it happen?
- Acetyl CoA turned into Malonyl CoA
- enzyme used: Acetyl CoA Carboxylase
- required coenzymes: ABC- ATP, Biotin, CO2
What are the 2 regulatory enzymes for de novo synthesis of fatty acids?
- Acetyl CoA Carboxylase MAJOR ONE
- Fatty acid synthase
What is the allosteric activator of Acetyl CoA Carboxylase? Allosteric inhibitor?
- activator: citrate
- inhibitor: long chain fatty acyl CoA like palmitoyl CoA
What enzyme in glycolysis does citrate allosterically inhibit?
PFK1
What is the difference between Acetyl CoA Carboxylase’s active form and inactive form?
- active: tightly connected, in a chain
- inactive: disconnected, scattered
What 4 enzymes are active in dephosphorylated state?
- Acetyl CoA Carboxylase
- glycogen synthase
- pyruvate kinase
- PDH complex
How is Acetyl CoA Carboxylase in the dephosphorylated state? How about the phosphorylated state?
- dephos: active
- phospho: inactive
What is insulin’s effect on Acetyl CoA Carboxylase (ACC)? What inhibits it ACC?
- activates it by promoting dephosphorylation
- epinephrine and glucagon promote phosphorylation and inactivates ACC
What type of diet stimulates ACC and fatty acid synthase? What diet decreases it? What protein mediates this process through insulin?
- stimulates: high carbohydrate
- inhibits: low carbohydrate
- sterol regulatory element binding protein (SREBP-1)
De novo synthesis of fatty acids is terminated by the formation of what?
Palmitic acid (16C)
What process is done to make a higher chain length of fatty acids? Where does it happen?
- elongation of fatty acids
- smooth ER
What is desaturation? Where does it happen? What is stearic acid turned into when desaturated? Palmitic acid? What enzyme and coenzymes are required for this to happen?
- double bonds added to fatty acids; saturated fatty acids give rise to unsaturated fatty acids
- smooth ER
- oleic acid
- palmitoleic acid
- desaturases; cytochrome b5, NADH, 02
What two essential polyunsaturated fatty acids can the body not synthesize? Why? How can we do it then?
- linoleic acid and linolenic acid
- can’t desaturate it because there’s an existing double bond already
- need to change linoleic acid to arcachidonic acid by desaturation and elongation
What components are required for TAG synthesis?
- Acyl CoA (activated free fatty acid)
- glycerol 3-phosphate
What are the two sources of fatty acid used in TAG synthesis?
- Chylomicron- from diet
- VLDL- from liver
What enzyme is used to activate fatty acid?
Acyl CoA synthase(thiokinase)
What are the two sources of Gylcerol 3-Phosphate?
- Glycolysis: glucose-> DHAP->glycerol 3P
- from free glycerol in liver( NOT ADIPOSE TISSUE): glycerol to gylcerol 3p with glycerol kinase
What hormone stimulates TAG synthesis under well fed conditions? At what sites?
- Insulin
- liver and adipose tissues
What mediates the insulin transportation of glucose into adipose cells?
GluT 4
What happens to the TAGs after they’re synthesized in the liver? Are the TAGs meant to store and save for later?
- transported out of liver through VLDL
- TAGs aren’t meant to store in the liver, this can lead to Fatty Liver
What happens to TAGs after synthesized in adipose tissue?
-it’s stored in adipose and saved until it needs to be degradated
