Exam 4 L1: Lipid Metabolism Flashcards
Explain what happens in the fed state to the rate limiting enzymes of lipid metabolism
Fed State: INSULIN
Activate Acetyl CoA Carboxylase (turning acetyl coA into Fatty Acyl-coA… eventually making TAGs)
Inhibit Carnitine Palmitoyltransferase I
Increase production of cholesterols from acetyl coA
Explain what happens to the rate limiting enzymes in lipid metabolism during the fasted state
Fasting State: EPI
Activates carnitine palmitoytransferase I (which takes fatty acyl-coAs and transports them into mitochondria where they are turned into acetyl coA)
Then HMG-CoA synthase is activated to turn the acetyl coA into ketone bodies (for brain functions)
During the fed state:
Fatty acids are transported as part of ___ or ____
During the fed state:
dietary TAGs are packaged as chylomicrons in the small intestine and enter the blood stream
synthesized TAGs enter the blood stream after being turned into “low density lipoproteins” in the liver
During the fasted state:
FAs are transported bound to ____
During the fasted state,
FAs are transported bound to albumin
TAGs are mobilized as fatty acids in the blood stream as “free fatty acids” but are essentially bound to albumin
Then the liver can make ketone bodies to supply energy for the brain
What fatty acid is the product of FA synthesis?
Which fatty acids are the omega 3 essential FA’s?
Which fatty acid is a precursor of prostaglandin?
Palmitic is the product of FA synthesis
Linoleic and Linolenic are the omega 3 essential FAs
Arachidonic is the precursor of the prostaglandins
“Free fatty acids” in the plasma are____-
“Free fatty acids” in the plasma are bound to serum albumin and are circulated in the blood stream
The equation for Fatty Acid Biosynthesis:
what is it? (remember, essentially, acetyl coA and malonyl coA are going to Palmitate)
Explain the role of Acetyl coA Carboxylase in the DeNovo biosynthesis of fatty acids
Fatty acid biosynthesis requires:
1.
2.
3.
4.
5
Fatty acid synthesis requires:
- acetyl groups - transported by citrate from the mitochondria into the cytoplasm
- acetyl-coA carboxylase (rate limiting enzyme)
- biotin - carrier of activated CO2
- Fatty Acid Synthase Complex
- NADPH
All carbons are derived ultimately from _____
Most ______ derive from _____ metabolism
All carbons are derived ultimately from acetyl coA
Most acetyl-coAs derive from carbohydrate metabolism
Citrate:
Stimulates _______ biosynthesis
Transports _____
Allosterically activates _____-
Citrate stimulates fatty acid biosynthesis
Citrate transports acetyl groups from mitochondria
Citrate allosterically activates acetyl coA carboxylase
Citrate is the carrier of _____ from the ____ to the ____
Citrate is the carrier of acetyl groups from the mitochondria to the cytoplasm
If there is an abundance of citrate, what does that mean?
Abundance of citrate means the TCA cycle is in robust activity, and additional acetyl coA can be converted and ultimately stored as TAGs
Explain the citrate shuttle
Essentially, the citrate shuttle transports citrate from the mitochondrial matrix to the cytosol.
Then citrate is used to make acetyl coA and oxaloacetate.
The acetyl coA goes onto Fatty Acid synthesis.
The oxaloacetate is regenerated into pyruvate, and in that process we form NADPH we gets utilized in fatty acid synthesis as well.
What is the rate limiting enzyme in Fatty Acid Biosynthesis?
What rxn does that enzyme catalyze?
What is the cofactor for that enzyme?
Acetyl CoA Carboxylase:
- Rate-Limiting Enzyme in Fatty Acid Biosynthesis
- Catalyzes the formation of malonyl-coA from acetyl-coA
- Biotin, a cofactor, serves as a carrier of activated CO2
Acetyl coA carboxylase rxn:
Acetyl coA + HCO3- + ATP ———->
Malonyl CoA + H20 + ADP + Pi
What are the activators and inactivators of acetyl CoA carboxylase?
Activators: Citrate and Insulin and Biotin
Inactivators: Palmitoyl CoA (end product inhibition) and Glucagon and Epi (promoting phosphorylation of the enzyme)
What is the product of the reaction synthesized by acetyl coA carboxylase?
What is the physiological significance of that product?
Product of acetyl coA carboxylase rxn: Malonyl coA
Malonyl CoA is the only physiological inhibitor of the rate limiting enzyme in fatty acid oxidation (carnitine palmitoyltransferase I)
Malonyl coA is also a key regulator of fatty acid oxidation and ketone body formation
Regulation of Acetyl CoA Carboxylase; SHORT TERM
allosteric activator and allosteric inhibitor
hormonal activator and hormonal inhibitor
SHORT TERM regulation of Acetyl coA carboxylase:
allosteric activator: citrate
allosteric inhibitor: palmitoyl coA and AMP
Hormonal activator: insulin (promotes dephosphorylation)
Hormonal inhibitor: glucagon and epi (promotes phosphorylation)
LONG TERM regulation of acetyl coA carboxylase:
Increased Enzyme Synthesis due to ….
Decrease Enzyme Synthesis due to….
Long Term Regulation of Acetyl CoA Carboxylase:
Increased Enzyme Synthesis: high carb diet, insulin, thyroid hormone, fat free diet
Decreased Enzyme Synthesis: high fat diet, fasting, glucagon
The Fatty Acid Synthase Complex :
catalyzes the formation of ____ from _____
The fatty acid synthase complex:
Catalyzes the formation of fatty acids (e.g. palmitate) from 1 Acetyl-CoA + 7 Malonyl CoA
Make sure you know the stoichiometry of the following eqn:
Acetyl CoA (2C’s) + 7 Malonyl CoA (21C’s) + 14 NADPH + 14 H+ ———>
Acetyl CoA (2C’s) + 7 Malonyl-CoA (21 C’s) + 14 NADPH + 14 H+ —————–>
Palmitate (16 C’s) + 7 Co2 + 14 NADP+ + 8 CoA + 6 H20
The fatty acid synthase complex catalyzes ____ reaction cycles
Fatty acid synthase complex catalyzes seven reaction cycles (approximately)
Name the steps of the fatty acid synthase complex (just give the general name for the steps)
Fatty Acid Synthase Complex Rxns
- Condensation
- Reduction
- Dehydration
- Reduction
Now explain each step in the fatty acid synthase complex
FIRST: acetyl coA gets added to an Acyl carrier protein, and so does malonyl coA to form butyryl ACP and malonate
Then during the condensation rxn: ace
What is the product of fatty acid biosynthesis?
What are the fates of that substance?
product of fatty acid biosynthesis: palmitate
Palmitate can then be elongated or desaturated
Ultimately, they are esterified to TAGs, phospholipids, and cholesterols
Regulation of the Fatty Acid Synthase Complex:
Short Term:
- Activator is _______
Long Term:
Regulation of FAS Complex:
Short Term:
Allosteric activator is Fructose 1, 6-bisphosphate
Long Term:
Increased E Synthesis: High carb diet, insulin, fat free diet
Decreased E Synthesis: Glucagon, High fat diet, fasting
PRARs promote _____
PRARs promote TAG deposition
