Block 3 Lecture 3 -- beta-Oxidation Flashcards
length of short chain FAs
2-4 C
length of medium chain FAs
4-12 C
length of long chain FAs
12-20 C
length of very long chain FAs
> 20 C
What is the most common trans fat?
elaidic acid
structure of elaidic acid
18:1-trans-∆9
structure of alpha-linolenic acid
18:3-cis,cis,cis-∆9,12,15
What are examples of omega-3 FAs?
alpha linolenic, EPA, DHA
Where are SCFAs activated?
cytosol or mitochondria
Where are MCFAs activated?
mitochondrial matrix
Where are LCFAs activated?
ER, outer mitochondrial membrane, or peroxisomes
Where do all activated FAs have to go for oxidation?
mitochondria
Where is carnitine derived from?
side chain of lysine
What is the function of the carnitine carrier system?
transporting LCFAs to mito matrix
What are the proteins associated with the carnitine carrier system?
1) CPT-1
2) CPT-2
3) translocase
What does CPT stand for?
carnitine:palmitoyltransferase
Where are CPT 1/2?
1 @ cytosolic side
2 @ matrix side
How is CCS regulated?
CPT-1 inhibited by malonyl-CoA
How many ATPs from beta-oxidation of C18 saturated FA?
146
4 steps of beta-oxidation?
1) FAD-dependent DH
2) hydration
3) NAD+ dependent DH
4) thiolysis
4 enzymes of beta-oxidation?
1) Aceyl-CoA DH
2) Enoyl-CoA hydratase
3) L-beta-hydroxyacyl DH
4) beta-ketoacyl thiolase
Describe the 2 problems during beta-oxidation.
1) beta-gamma double bond
2) ∆4 conjugated system
How is a beta-gamma double bond fixed?
isomerase (- 2 ATP since it skips the FAD-dependent DH step)
How is a ∆4 conjugated system fixed?
reductase (-3 ATP since it requires NADPH)
How many ATP from an 18:0?
146
How is beta-oxidation regulated?
indirectly by demand for ATP
- reoxidation of FADH2/NADH during the ETC
- produced acetyl-CoA enters TCA cycle
What is Zellweger’s syndrome?
inherited deficiency of peroxisomes causing accumulation of VLCFAs, especially in the brain
What is the indication for clofibric acid and clofibrate?
hyperproteinemia and hyperlipidemia
What is the MoA for clofibric acid and clofibrate?
stimulate peroxisomes to oxidize VLCFAs
What are omega-3’s supposedly good for?
solubilizing cholesterol & TG’s without sticking to arteries by forming a micelle of sprirals
Why are trans fats bad?
isomerase cannot move trans-beta-gamma to trans-alpha-beta for oxidation; so fatty chain accumulates in arteries
What are the 2 major anaplerotic pathways for the TCA?
1) propionyl-coA carboxylase
2) pyruvate carboxylase
What cofactors are required by carboxylases?
biotin
What step in converting propionyl-CoA to succinyl-CoA requires B12?
methylmalonyl-CoA mutase
What’s the end product of odd-numbered FA beta-oxidation?
propionyl-CoA
When is peroxisomal beta-oxidation used?
for VLCFAs
How many fewer ATPs less per cut in peroxisomal compared to regular beta-oxidation?
2 less
Why 2 fewer ATPs in peroxisomal?
FADH2 can’t be transported to mitochondria
What is the product of peroxisomal beta-oxidation?
C8-acyl-CoAs (transported via carnitine carriers)
Where does omega-oxidation occur?
in the ER
When does omega-oxidation occur?
normally a minor role unless beta-oxidation is compromised (ex carnitine deficiency)
What is the product of omega-oxidation?
C6-8 omega-COOH’s excreted in the urine
How does omega-oxidation work
1) CYP450 oxidizes omega end to OH
2) 2 NADP-dependent DH’s oxidize to omega COOH
3) omega oxidation stopping at C6-8
On what molecules does alpha-oxidation occur?
VLCFAs (primarily branched FAs from plants)
Where does alpha-oxidation mainly occur?
brain/nervous tissue
How does alpha-oxidation occur?
1) alpha H oxidized to alpha-OH
2) NADP-dependent DH to make alpha-ketone
3) NADP dependent decarboxylation
4) beta oxidation yields variety of products
Which ketone body is the most stable/energy rich?
d-beta-HB
How are ketone bodies synthesized?
from 2 A-CoA in 3 steps
1) thiolase
- - claisen condensation
2) HMG-CoA synthase
- - claisen condensation + hydrolysis
3) HMG-CoA lyase
- - aldol/claisen cleavage
Where are ketone bodies synthesized?
mitochondria of liver
What are the fates of acetoacetate?
1) decarboxylation to acetone
2) D-beta-HB-DH to D-beta-HB (determined by NADH/NAD+ ratio)
Which ketone body is directly used for energy in tissue?
acetoacetate
– D-beta-HB must be oxidized to give NADH
How is acetoacetate converted to Acetyl CoA?
1) ketoacyl transferase (transesterification) to acetoacetyl-CoA
2) thiolase –> 2 acetyl-CoA
What is the cost of activating acetoacetate?
1 ATP equivalent that would have been derived from succinyl CoA
Where is acetoacetate activated?
mitochondria (not in liver!)
How many ATP from d-beta-HB?
23 (2*2Acetyl-CoA - 1 lost to activation)
Why are fatty acids synthesized in fasting?
low malonylCoA levels, activating CPTI
Why are ketone bodies synthesized in fasting?
low OAA levels, accumulation of acetyl CoA
Which KB is produced most during fasting?
beta-d-HB
What causes alcohol-related ketoacidosis?
1) low [glycogen]
2) NADH from acetaldehyde blocks lactate DH
3) FAs released, KBs synthesized
How are fatty acids preferred in muscle?
high [acetyl coa] inhibits pyruvate DH through phosphorylation
