Lect 7 Lipid Degradation Flashcards
What size FA can diffuse into Mitochondria?
Short Chain FA (SCFA)
Medium Chain FA (MCFA)
What size FA need to be actively Transported?
Long Chain FA (LCFA)
Very Long Chin FA (VLCFA) - Oxidized in Peroxisomes down to LCFA
What is the process of Phase I of FA Catabolism (Transport into Mitochondria)
How do LFCAs get into mitochondria?
What is the rate limiting enzyme located in the intermembrane space? How is it regulated?
How does it get into the mitochondria matrix for breakdown?
What enzyme in the inner membrane converts it back to CoA?
- Cytosol: LFCAs + CoA –> Fatty Acyl CoA (via fatty acyl CoA synthetase on outer membrane) –> Crosses outer membrane
- FA-CoA + Carnitine (CPT1/Carnitine Palmityltransferase I or Carnitine Acyltransferase) –> FA Carnitine
-
Rate Limiting Enzyme in FA Degradation
- Inhibited by Malonyl CoA
-
Rate Limiting Enzyme in FA Degradation
- FA Carnitine –> Matrix via Carnitine-Acylcarnitine Translocase (CACT)
- Antiporter: FA-Carnitine in - Carnitine out
- CPT-II (inner membrane) transfers CoA to FA-Carnitine –> FA-CoA (Matrix)
What are the Typical FA Features
Saturated
Even numbered carbon chain
16-20 carbons
What are the products of B-Oxidation
Acetyl CoA (TCA)
FADH2 (e- to CoQ/ubiquinone of ETC)
NADH (e- to Complex I of ETC)
What are the steps in Phase II (B-Oxidation in Matrix)
What enzyme is in the first step? Product?
Product of step 3?
How many times is process repeated?
-
Oxidation: Acyl CoA Dehydrogenase (ACAD)
- FAD –> FADH2
- SCAD, MCAD (defects most common), LCAD, VLCAD
- Hydration: Enoyl acyl CoA Hydratase
-
Oxidation: B-hydroxyl acyl CoA dehydrogenase
- NAD+ –> NADH
-
Thiolysis: Acyl CoA Acyltransferase (ketothiolase)
- Acetyl CoA formed (shortens FA by 2C
- Process Repeated 7 times total
What is the B-Oxidation Stoichiometry
Palmitate + 7 FAD + 7 NAD+ + 7 CoA + 7 H2O <—> 8 Acetyl CoA + 7FADH2 + 7NADH + 7H+
What is the first product of B-Oxidation of Odd Numbered FAs
What enzyme metabolizes the odd number FA
What is the final product and where does it go?
- Proprionyl CoA (3C)
- Proprionyl CoA Carboxylase (Biotin + ATP) carboxylates –> Methylmalonyl CoA (4C)
-
Methylmalonyl CoA Mutase converts to Succinyl-CoA
- Succinyl-CoA enters TCA cycle
What happens during B-Oxidation of Unsaturated FAs
What enzymes are used?
- Metabolized until unsaturation is reached
- Reductase reduces double bond
- Isomerase moves the disruptive bond
VLCFAs - Peroxisomal B-Oxidation
When does Peroxisome B-Ox shift to Mitochondria?
Energy differences?
What toxic substance is produced and how is it dealt with?
Differences to normal B-Ox?
- Metabolized until < 20C –> Mitochondria
-
Does not produce ATP
- e- transferred to O2
- Produces H2O2 –> Catalase converts to H2O and O2
- First step is catalyzed by acyl CoA oxidase (not acyl CoA Dehydrogenase)
What is MCAD Deficiency?
What does it lead to?
What are the consequences?
What energy source becomes only option?
- Impairs breakdown of MCFAs
- Leads to Secondary Carnitine Deficiency
- C8 FA accumulates in liver, interferes w/ urea cycle and increased levels of ammonia
- Patients depend on glucose as energy source
Why are Ketone Bodies Formed
Fasting/Starving Conditions = Excessive B-Ox of FAs –> Increased Acetyl CoA
Ketone Body Features
Water Soluble and Acidic Compounds
Produced in Liver only
Provide energy for peripheral tissues and brain
Primary Ketone Body Names
Acetoacetate
B-Hydroxybutyrate
Acetone
Ketone Formation
- 2 Acetyl CoA –> Acetoacetyl CoA –> HMG CoA –> Acetoacetate –> B-Hydroxybutryate OR Acetone
