Figure this out by the end of the lecture
Overview of Fatty Acid Metabolism
Why is fatty acid storage more compact and a better energy storage than glycogen?
Smaller molecule
Larger molecule
Hydrophobic Effect
Ionic effect
Hydrophobic Effect
What are Fatty Acids?
Palmitate
Palmitolate
Stearate
Oleate
Linoleate
Linolenate
Arachadonic Acid
Biological Functions of Fatty Acids
Triacylglycerol
Membrane Structures
Release of FA from Adipose and the Enzymes involved.
Triglyceride Degredation
When fatty acids are released from the fat cell they are carried by serum albumin?
They are specific receptors for serum albumin on tissues, but not for fatty acids
The fatty acids would precipitate in serum unless bound to albumin
The fatty acids would bind to membrane components and not travel to target tissues
the fatty acids can only enter the nerves system if bound to albumin
The fatty acids would precipitate in serum unless bound to albumin
How long must a chain be to be soluble?
Once you get larger than 8 carbon fatty acids it starts to precipitate
What Carries FA in the Blood? and Why?
Albumin is the most abundant protein in your blood stream.
What other protein is activated by PKA
Liver phosphorylase (activated by phosphorylase kinase)
Muscle Phosphorylase
Protein phosphatase 1
Protein Inhibitor 1
glycogen synthase (Inhibited by PKA)
Protein Inhibitor 1
What Happens to the Glycerol Produced?
G3PDH is also needed for what pathway?
Glycolysis
Glucogneogeneiss
An electron shunt pathway
Glycogen Degredation
Glycogen synthesis
An electron shunt pathway
How many high-energy phosphate bonds are required to convert two molecules of glycerol to one molecule of glucose in the liver?
0
1
2
3
4
5
6
2
Lactate requires 6 Atps to get to Glucose but glycerol only needs 2. But there’s much more Lactate than Glycerol.
What Happens to the Fatty Acids?
Feeding Experiments
Beta Oxidation
Similarities to TCA Cycle
Fatty Acid Oxidation Reactions
Big Picture of Fatty Acid Oxidation
Fatty Acid Oxidation
Overview of Fatty Acid Oxidation
Fatty Acid Transport into the Mitochondria
Acetyl CoA vs. Acyl CoA
Acetyl CoA — this specifies that the CoA is directly linked to the Acetyl group.
Acyl CoA— Hydrocarbon chain linked to CoA
What would you expect to happen in fan individual had a CPT II deficiency?
Fasting Hyperglycemia
Fasting Hypoglycemia
Reduced glycolytic rate
No effect on metabolism
Fasting Hypoglycemia — Liver will have trouble maintaining blood glucose levels.
Oxidation of Saturated Fatty Acids
Acyl-CoA Dehydrogenase
Peroxisomal Fatty Acid Degredation
For the complete oxidation of palmitic acid, how many rounds of the beta oxidation spiral are required?
5
6
7
8
9
7— after 6 rounds we released 6 acCoA (12 carbons) we started with 16 so that leaves 4 carbons so we have one more round to get to 7
Energy Yield from Fatty Acid Oxidation
Oxidation of Unsaturated Fatty Acids
Unsaturated Fatty Acids Continued
Unsaturated FA pt. 3
Unsaturated FA Pt. 4
Unsaturated FA Pt. 5
ATP Yield from Unsaturated Fatty Acid
Which fatty acid when completed oxidized will yield the greatest amount of ATP?
C16:0
C18:0
Cis delta 5 C20:1
Cis Delta 6 C20:1
Cis Delta 6,9 C20:2
Cis delta 5 C20:1
Oxidation of Odd-Chain Fatty Acids
ATP from the Oxidation of an Odd Chain Fatty Acid
Alpha Oxidation
Alpha oxidation is unique to branched chain fatty acids.
Omega Oxidation
Only see Omega oxidation when Beta Oxidation is working.
Omega converts methyl group to alcohol then aldehyde then to an acid
Why is alpha oxidation required for Phytanic Acid?
To allow the hydration step to occur
to Allow the acyl CoA dehydrogenase step to occur
To allow the thiolase step to occur
To allow the hydroxylacyl CoA dehydrogenase step to occur
To allow the hydroxylacyl CoA dehydrogenase step to occur —
Methyl group is on the beta carbon. SO we can do the first step fine. The second step is to add hydroxyl group on the beta carbon. The third step is to oxidize the hydroxyl group on the beta carbon therefore we can’t make a ketone on that carbon. So if you use alpha oxidation you move the methyl group to the alpha position and can therefore oxidize the beta position.
What metabolite may accumulate in the blood of an individual with MCAD deficiency?
Free Fatty Acids
Carnitine
6-10 Carbon Dicarboxlic acids
Glucose
Glycerol
6-10 Carbon Dicarboxlic acids — This is a case where omega oxidation will take over. Organic Dicarboxylic acids will be released.
How does FA derived from FADH2 Deliver Electrons to the ETC
Ketone Bodies
Biosynthesis of Ketone Bodies
How are ketone bodies metabolized
Regulation of Ketone Body Synthesis
Timing of Fatty Acid and KB utilization
Metabolic Defects in FA oxidation
Carnitine Deficiency
Fatty acids accumulate in the cytoplasm because they can’t get into the cytoplasm. SO FA in liver and muscle are disease conditions and this is why.
Primary — Treat with Short Chain Fatty acids.
Secondary — can’t be treated with short chain.
We don’t make ketone bodies with either type of Carnitine Deficiency.
Primary Carnitine Deficiency
Secondary Carnitine Deficiency
MCAD Deficiency
4 Peroxisome Disorders
Zellwedgers Syndrome
Refsum Disease
Adrenoluekodystrophy
Acyl-CoA Oxidase Deficiency
Zellwedger Syndrome
Refsum Disease
Adrenoluekodystrophy
Acyl-CoA Oxidase Deficiency
Jamacan Vomiting Sickness
Fatty Acid Bioxynthesis Rationale and Reactions
Pathway of FA Biosynthesis
Initial Condensation
Initial Condensation Cont.
Reductions of Dehydrations
Reduction and Condensation
Elongation of Fatty Acids
Desaturation of Fatty Acids
Essential Fatty Acids
Elongation and Desaturation of Fatty Acids – Omega Series
Omega Series Cont.
Transport of Acetyl CoA
Regulation of Fatty Acid Metabolism
Hormonal Regulation of Fatty Acid Metabolism
Allosteric Regulation of Fatty Acid Metabolism
Glucagon Regulation of Fatty Acids
Good Question. You better Damn Well Know the Answer!!!