Flashcards in Fatty Acid Metabolism 1 Deck (48):
What is the most effective way the human body has of storing energy?
Pound for pound Triacylglycerols (TAGs) contain about 6.75 times as much energy as Carbs (e.g. Glycogen).
What structural component related to cellular biology is composed of lipids?
The phospholipid bilayer.
Describe the structure of Triacyglycerol.
A glycerol back bone with three fatty acid groups bonded in place of the hydroxyl groups.
What is the major dietary source of carbon for fatty acid synthesis?
In what organ does fatty acid (FA) synthesis primarily occur?
Primarily in the liver, but can also be synthesized in adipose tissue, brain, kidneys, and lactating mammary glands.
Fatty acid synthesis requires coordination between reactions in what two locations?
Cytosolic reactions and mitochondrial reactions.
What are the two ends of a fatty acid referred to as?
There is a Carboxyl end with a carboxyl group, and a methyl end with a methyl functional group.
What is the precursor for fatty acid synthesis?
Acetyl-CoA (a 2 carbon molecule)
Where is Acetyl-CoA synthesized?
In the mitochondria.
What is the characteristic event signifying the first phase of fatty acid synthesis?
The movement of Acetyl-CoA from the mitochondria into the cytoplasm. It however, can not diffuse across the membrane.
How does Acetyl-CoA move into the cytoplasm from the mitochondria?
Acetyl-CoA is combined with Oxaloacetate via a condensation reaction catalyzed by Citrate Synthase which product is Citrate. Citrate can then cross the mitochondrial membrane via a citrate transporter.
What characterizes the second phase of fatty acid synthesis?
Acetyl-CoA is carboxylated to malonyl-CoA. This is the most important substrate in FA synthesis. This is also a rate limiting reaction in the synthesis of fatty acids.
Once citrate (Acetyl-CoA and Oxaloacetate) is in the cytosol, what is the next step in fatty acid synthesis?
The next step is converting citrate back to oxaloacetate and acetyl-CoA via the enzyme ATP Citrate lyase.
What stimulates and inhibits ATP Citrate Lyase?
Glucose and insulin stimulate. PUFA's and leptin inhibit.
Once acetyl-CoA is in the cytosol it is converted to Malonyl CoA by what enzyme? Is this an exergonic or endergonic reaction?
Acetyl CoA carboxylase. This is a rate limiting step! This is an endergonic reaction (delta G >0) as it requires 1 ATP. It also uses Biotin as a co-factor.
What is acetyl CoA carboxylase (Acetyl CoA to Malonyl CoA) inhibited and stimulated by?
Acetyl CoA carboxylase is inhibited by Glucagon, epinephrine, high [AMP], palmitate, and PUFA. It is stimulated by Citrate and Insulin.
Once Oxaloacetate is separated from acetyl CoA in the cytosol, what is it's fate?
It is converted to Malate via malate dehydrogenase (requires NADH2) where it can then be transported back into the mitochondria or continue to be converted to Pyruvate via malic enzyme (creates an NADH2) where it can then be transported back into the mitochondria.
How is the TCA cycle involved in fatty acid synthesis?
Oxaloacetate is a substrate used in the TCA cycle. It is also used to transport Acetyl CoA into the cytoplasm. The oxaloacetate is returned to the mitochondria after it has undergone reactions to remove acetyl CoA in the cytoplasm.
What is the rate limiting step in Phase II of fatty acid synthesis?
The conversion of Acetyl CoA to Malonyl CoA via Acetyl CoA carboxylase.
What are the characteristic steps of the third phase of fatty acid synthesis?
The enzyme Fatty acid synthase catalyses 7 reactions that incorporate Acetyl CoA and Malonyl CoA into palmitate, a C16 fatty acid.
What is a product of fatty acid synthesis, and also an inhibitor of fatty acid degredation?
Malonyl CoA. It inhibits carnitine acyltransferase which is used in the rate limiting step of fatty acid degradation.
What is the product of fatty acid synthesis?
A fatty acid (duh) named Palmitate with 16 carbons.
How many Carbons are added to fatty acid chain at a time during fatty acid synthesis and what complex does this?
2 carbons are added from malonyl CoA at a time. This is completed 7 total times resulting in palmitate, a 16 carbon fatty acid. This is completed via the fatty acid synthase complex.
Describe the composition of the Fatty Acid Synthase (FAS) complex.
- Large multi-enzyme complex
- Composed of 2 identical dimers arranged in a heat to tail formation to create an oval
- Each dimer has 7 enzyme activities and an acyl carrier protein.
What is a unique characteristic of the Acyl carrier protein (ACP) on the FAS.
FAS = Fatty acid synthase.
ACP has a flexible arm that "picks up a substrate and puts it on the next enzyme.
Stoichiometry of the Palmitate Synthesis Reaction (know big players)
1 Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14 H+ = CH3(CH2)v14C00- + 14 NADP+ + 8 CoA +6 H2O
What is the reaction pattern carried out by the FAS?
FAS = Fatty acid synthase
How many carbons are in Acetyl CoA?
How many carbons are in Malonyl CoA?
How many carbons are in the molecular product after the first pass through the FAS complex?
How many carbons are there in the final product of the FAS complex?
How many carbons are get added to the product with each cycle of the FAS?
2, 3, 4, 16, 2
What are the 3 points of regulation in fatty acid synthesis?
1. ATP citrate lyase (phase I)
2. Acetyl CoA Carboxylase (phase II)
3. Fatty Acid synthase (phase III)
What is the role of ATP Citrate lyase in fatty acid synthesis, and how is it regulated?
Its role is to release Acetyl CoA from oxaloacetate once it citrate has entered the cytoplasm. It is stimulated by phosphorylation. Its gene expression is induced by glucose/insulin. The induction of its gene expression is counteracted by polyunsaturated fatty acids (PUFAs) and leptin.
What is leptin and what is its role in fatty acid synthesis?
Leptin is a hormone released by adipose tissue that inhibits hunger. It counteracts the gene expression of ATP citrate Lyase which would cause excess citrate to build up in the cytoplasm and be unable to stimulate the fatty acid synthesis process.
What enzyme catalyzes the rate limiting step in FA synthesis?
Acetyl CoA Carboxylase (ACC).
FA = fatty acid.
What stimulates ACC in FAS?
ACC= Acetyl CoA Carboxylase
It is stimulated by the presence of Citrate in the cytoplasm. Insulin stimulates ACC via activation of protein phosphate. Gene expression is up-regulated by high carb/low fat diet.
What inhibits ACC in FAS?
ACC = Acetyl CoA Carboxylase. FAS = Fatty Acid Synthesis.
ACC is inhibited by long chain fatty acids (palmitate), Epinephrine and Glucagon via activation of protein kinase A, and AMP via activation of AMP kinase (energy sensor)
What did the leptin knockout mice show?
Mice lacking leptin became obese but lost weight when given leptin. This supported the hypothesis that leptin regulated body weight by inhibiting food intake and stimulating energy expenditure.
What is the longest Fatty acid chain that can be made in the cytosol?
Palmitate, which in 16 carbons in length and the product of FAS.
Where can Fatty acid chains longer that 16 carbons be made?
With in the smooth endoplasmic reticulum (SER) or the Mitochondria.
What body organ requires longer chain fatty acids (C18-C24)?
What does the SER use as a carbon donor to elongate palmitate?
SER = Smooth endoplasmic reticulum
The carbon donor in the SER is Malonyl CoA.
What does the Mitochondria use as a carbon donor to elongate palmitate?
Can FA become unsaturated in the body? If so where?
Fatty acid desaturation occurs in the SER. It is completed with the use of NADPA (or NADH) and oxygen. It is catalyzed by Acyl CoA Desaturases. Human Desaturases can only introduce double bonds in the 4,5,6, and 9 position.
Can a FA with a Double bond at its 12 carbon be synthesized by humans?
No, humans can only synthesize fatty acids with double bonds at the 4, 5, 6, and 10 position.
What induces FA desaturases gene expression? What suppresses FA desaturases gene expression?
Insulin induces gene expression, and dietary PUFAs suppress. Dietary Cholesterol induces expression of delta-9 desaturase, and suppresses all others.
Can humans synthesize omega-3 or omega-6 fatty acids?
No, they must be ingested.
What are the precursors to omega-3 or omega-6 fatty acids called?
Essential Fatty Acids
What is Linoleic acid used to make?
Linoleic acid = Omega 6 fatty acid
It is used to make arachidonic acid which is a precursor for many important molecules.
What is Linolenic acid used to make?
Linolenic acid is used to make eicosapentanoic acid (EPA) (20:5 omega3) and docosahexanoic acid (DHA)