Lipid Synthesis and Storage (Biochem) Flashcards
What is the rate-limiting enzyme of FA synthesis?
- Acetyl CoA carboxylase
- ABC enzyme* (requires):
A: ATP
B: Biotin
C: CO2 - activation by insulin (dephosphorylated)
- activation by citrate
- this is like pyruvate carboxykinase, which is aslo an ABC enzyme
Essential FA
- linoleic C18:2 (9,12)
- linolenic C18:3 (9,12,15) (omega 3 family)
- found in fish oil, flax seed oil
Omega 3 FA
- ex) Linolenic
- Assoc w decreased risk of cardiovascular disease and
- decrease in serum TG
- found in cold-water fish (salmon, tuna, herring)
- found in some nuts (walnuts) and seeds (flax seed)
How do omega 3 FA correlate with a decreased risk of cardiovascular disease?
- appear to replace some of the arachidonic acid (an omega 6 FA) in platelet membranes
- may lowe the production of thromboxane and the tendency of platelets to aggregate
FA synthesis occurs in the
cytoplasm
when FA are used in metabolism, they are first ___
- activated by attaching coenzyme A (CoA)
- Fatty acyl CoA synthetase catalyzes this activation step
Lipid Digestion
- upon entry into the intestinal lumen, bile is secreted by the liver to emulsify the lipid contents
- the pancreas secretes pancreatic lipase, colipase, and cholesterol esterase that degrade the lipids to 2-monoglyceride, FA, and cholesterol
- these lipids are absorbed and re-esterified to TG and cholesterol esters and packaged into chylomicrons
- Normally, there should be very little lipid loss in stools
- defects in lipid digestion result in steatorrhea = excessive ant of lipids in stools (fatty stools)
Excess glucose can be converted to
- FA in the liver
- and subsequently sent to adipose tissue for storage
Insulin promotes many steps in the conversion of glucose to Acetyl CoA in the liver. These include:
- Glucokinase (induced)
- PFK-1/PFK-2 (PFK-2 dephosphorylated)
- Pyruvate dehydrogenase (dephosphorylated)
citrate shuttle
- transports acetyl CoA groups from the mito to the cytoplasm for FA synthesis
- Acetyl CoA combines with Oxaloacetate (OAA) in thematic to form citrate
- this citrate goes into the cytoplasm (rather than entering the CAC)
- This process is indirectly promote by insulin and high [ATP]
- in the cytoplasm citrate lyase splits citrate back into acetyl CoA and OAA
- the OAA returns to the mitochondria to transport additional CoA into the cytoplasm
malic enzyme
- Converts malate to pyruvate*
- requires NADP+ and produces NADPH
- this supplements the cytoplasmic [NADPH]
- Acetyl CoA can’t exit the mitochondria, so it is converted to citrate to be transported into the cytoplasm
- citrate is converted back to OAA
- OAA is converted to malate
Both of the major enzymes of FA synthesis are also affected by insulin. these are:
- Acetyl CoA carboxylase (dephosphorylated, activated)
- FA synthase (induced)C
Acetyl CoA carboxylase
- Acetyl CoA is activated in the cytoplasm for incorporation into FA by acetyl CoA carboxylase
- is the rate-limiting enzyme of FA biosynthesis
- stimulated by insulin
- inhibited by glucagon
- insulin and glucagon regulate via phosphorylation and dephosphorylation
What FA do we make from scratch?
- Palmitate (16:0)
- Acetyl CoA carboxylase: Acetyl CoA to malonyl CoA
- FA synthase: malonyl CoA to Palmitate
citrate lyase
- in the cytoplasm
- splits citrate back into Acetyl CoA (from glycolysis) and OAA
- part of the process by which Acetyl CoA enters the cytoplasm for FA synthesis, bc Acetyl CoA can’t leave the mitochondria
FA synthase
- converts malonyl CoA to Palmitate
- requires NADPH (to reduce the acetyl groups)
- gives off CO2
- induced by Insulin
- contains an acyl carrier protein (ACP) that require the vitamin pantothenic acid (Vitamin B5)
- the FA is derived ENTIRELY from acetyl CoA
- ingredients: 8 Acetyl CoA, NADPH, CO2, ATP
Mechanism by which Alcoholics may develop fatty liver
Alcohol disrupts VLDL synthesis, so the FA created in the cytoplasm can’t exit the hepatocytes, and develop fatty liver
FA synthesis is regulated on 3 levels
- allosterically
- genetically
- by phosphorylation