Lipid Synthesis

Fatty Acid Synthesis vs β-Oxidation

 SynthesisDegradation
Greatest Flux Through PathwayAfter Carbohydrate-Rich MealIn Starvation
Hormonal State Favoring PathwayHigh Insulin / Glucagon RationLow Insulin / Glucagon Ration
Major Tissue SitePrimarily LiverPrimarily Mitochondria
Subcellular LocationPrimary CytosolPrimarily Mitochondria
Carriers of Acyl /Acetyl Groups Between Mitochondria and CytosolCitrate ( mitochondria to cytosol )Carnitine ( Cytosol to Mitochondria )
Phosphopantetheine-Containing Active CarriersAcyl Carrier Protein Domain , Coenzyme AConenzyme A
Oxidation / Reduction CoenzymesNADPH ( reduction )NAD+ , FAD ( oxidation )
Two-Carbon Donor / ProductMalonyl CoA: Donor of 1 acetyl groupAcetyl-CoA: Product of β-Oxidation
ActivatorCitrate 
InhibitorLong-Chain Fatty acyl-CoA ( inhibits acetyl-CoA carboxylase )Malonyl CoA ( inhibits carnitine palmitoyltransferase-1 )
Product of PathwayPalmitateAcetyl-CoA
Repetitive Four-Step ProcessCondensation ,Reduction , Dehydration , ReductionDehydrogenation , Hydration , Dehydrogenation , Thiolysis

Discuss the metabolic rationale for phosphorylation of acetyl-CoA carboxylase by AMP-activated protein kinase (AMPK) and cyclic AMP-dependent protein kinase (PKA)

-oxidationFatty Acid Synthesis
CatabolicAnabolic
Location = mitochondriaLocation = cytoplasm
Separate soluble enzymes are used1 multifunction enzyme is used
Acyl Carrier = CoAAcyl Carrier = Protein bound phosphantethiene
NAD , FADNADP
Precursors = Fatty acyl CoA
Products = Acetyl CoA
Precursors = Acetyl CoA and Malonyl CoA
Products = Fatty Acid Chains
Regulation = Substrate AvailabilityRegulation = Allosteric

Would it be possible to synthesize a fatty acid in mammalian cells starting from a C-16 or C-18 carbon fatty acid? Explain

What is the system name for a C-18 fatty acid? Is such a fat essential? How do you know?

What is the system name for a C-18 fatty acid? Is such a fat essential? How do you know?

Explain why adipocytes ( fat cells ) need glucose to synthesize triglycerides.

How does this Acetoacetate act to fuel contraction in cardiac myocytes?

Even in the presence of acetoacetate, pyruvate is required to maintain flux through the citric acid cycle. Explain

About ninety percent of the cholesterol used in cell membranes is synthesized in the liver. The rest is obtained from dietary sources. A single enzyme controls the entry of carbons into cholesterol biosynthesis. What enzyme is it? What molecules are given to individuals to lower endogenous cholesterol production?

Triglyceride

Glycerophospholipids

Sphinolipids

Triacylglycerols

How is glycerol-3-phosphate made using intermediates in central metabolism? What metabolic pathway is this similar to? How is it different?

Which method is used in adipocytes and why?

Now that we have Glycerol-3-phosphate, two fatty acids are added via esterification reactions. What class of lipids are generated in this step?

Are fatty acids Activated?

Phosphatidic acids have two fatty acid chains, but triacylglycerols have three. What remaining steps must take place in order for triacylglycerol synthesis to be completed?

Glycerophospholipids

Similar to triacylglycerols, the glycerophospholipids use phosphatidic acid as a precursor, indeed phosphatidic acids are glycerophospholipids themselves. What are the six main phospholipid classes found in our membranes?

https://en.wikipedia.org/wiki/Membrane_lipid#Major_classes

In order to modify the phosphate group on the phospholipid it must first be activated. How is the phosphatidic acid activated?

In order to make what molecule must be added to CDP-diacylglycerol and where?

Inositol group replaces CDP-diacylglycerol

Sphinogolipids

What are the two molecules needed to make sphingosine? How is this different from triacylglycerol and phospholipid synthesis?

What must be added to sphingosine (and where) in order to make a ceramide? Is this an esterification reaction?

What is added to a ceramide to make sphingomyelin? What other group of lipids is this similar to?

Cerebroside is in the class of lipids called glycosphingolipids. What molecules must be added to ceramide to make this class of lipids?

New carbon units are loaded onto which subunit of fatty acid synthase?

What is reduced in each round of fatty acid synthesis?

The beta carbonyl carbon of the acyl chain

How is the two-carbon building block for fatty acid synthesis moved from the mitochondrial matrix into the cytosol?

Citrate shuttle

Which of the following enzymes catalyzes the rate-limiting step in sterol synthesis?

HMG-CoA reductase

What is oxidized in each round of fatty acid synthesis?

NADPH

Which molecule enters as the new carbon units in fatty acid synthase?

Malonyl-CoA

How many cycles of fatty acid synthesis are required to synthesize a palmitate?

7

Which of the following is the correct sequence of events in cellular fatty acid biosynthesis?

Citrate shuttle → Acetyl-CoA Carboxylase → Fatty Acid Synthase

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