Beta-Oxidation Flashcards
What does the following notation represent in relation to lipids: 18:1?
18 carbons with one double bond
How is hormone sensitive lipase regulated?
Deactivated by Insulin, Activated by glucagon, epinephrine and norepinephrine
How are fatty acids activated?
By linkage to CoASH catalyzed by Fatty acyl CoA synthetase. First link to AMP with PPi as product (use ATP)
Where does B-oxidation occur?
In the Mitochondria Matrix
How does palimtoylCoA cross the impermeable membrane into the matrix?
The carnitine shuttle
How does the Carnitine Shuttle work?
1.Fatty acyl CoA diffuses through outer membrane 2.CPT I exchanges the CoA for carnitine 3.Fatty acylcarnitine transported through anti porter by Carnitine: acylcarnitine translocase (FA car. in, car out) 4.CPT II exchanges carnitine back for CoA
What is the major regulator of FA metabolism?
CPT I
How is CPT I regulated?
Allosteric Inhibition by Malonyl-CoA. Acetyl CoA is converted to Malonyl CoA by ACC, and ACC is inhibited by AMP and activated by insulin
What is the effect of CPT II deficiency?
first it’s an autosomal recessive trait, Adult onset is characterized by muscle pain, weakness, myoglobinuria after prolonged exercise or fasting. Neonatal and Infant Onset: Irritability, FTT, often fatal
What happens in one cycle of B-ox.?
OHOC Ox., Hydration, Ox., Carbon bond cleavage
What are the four main enzymes involved in B ox. in order and substrates?
Acyl-CoA Dehydrogenase (FAD-FADH2), Enoyl-CoA-Hydratase (H2O), Hydroxyacyl-CoA Dehydrogenase (NAD+-NADH), Thiolase (CoA-SH)
How many ATP are made per cycle of B ox.?
14 ATP (but minus 2 ATP for Fatty acyl CoA synthetase)
What is MCAD?
Medium Chain Acyl-CoA Dehydrogenase deficiency.
Infants get:
Reye Syndrome (swelling of brain and liver)
Fasting hypoketotic hypoglycemia
hepatic encephalopathy (brain damage because of liver fail)
SIDS
How is MCAD diagnosed?
Lipid profile in the blood (lots of it)
identification of mutations in the ACDH gene
What is the MCAD prognosis?
If caught before hypoglycemic episodes not bad. Improves with age
What is Jamaican Vomiting sickness?
Similar to MCAD. Caused by toxin from the ackee fruit. Usually not fatal.
What enzyme compensates for cis fatty acids/ wrong place for double bond?
Enoyl CoA Isomerase and 2,4-Dienoyl CoA reductase (second uses NADPH)
What is more useful to the cell B ox. of unsaturated or saturated fats?
saturated. No extra enzymes.
How are odd chain FAs taken care of and by what enzymes?
PropionylCoA is carboxylated (ATP and HCO3- used) by propionyl CoA carboxylase into methylmalonyl CoA and then made into succinyl CoA by methylmalonyl CoA mutase
What are and where are VL chain FAs oxidized
<22C. Degraded by peroxisome
How is VL ox. different than B ox.?
First step donates electron to O2 rather than FAD and instead of producing energy in FADH2 H2O2 is produced. When 4-6C are left the FA along with the acetyl CoA is transported back to the mito. matrix by carnitine based transport
Can humans produce branched chain FAs?
No. Plants only
How and where are branched FAs oxidized?
They are broken down in the peroxisome like VL FAs but the first carbon is ox. to CO2 by alpha ox.
What is omega-ox and where, how, and why does it take place?
Ox. on omega carbon. Takes place in the ER by Cytochrome P450. Fat made to a Dicarboxyl FA. Then broken to M Chain FA to be used elsewhere or excreted in urine.
What happens if glucose is used up and the liver’s storage of glycogen is depleted?
Keton bodies are formed to be used in the brain
Name the three ketone bodies
3-Hydroxybutyrate, acetoacetate, and acetone.
Where are ketone bodies formed?
The liver
How does the body signal to make ketone bodies?
increased B-ox. increases NADH and acetyl CoA. The increased NADH drives the TCA cycle backwards and oxaloacetate is converted to malate which is used for glu gen. The low oxaloacetate diverts acetyl CoA into ketone body sun rather than TCA
How are ketone bodies synthesized? What enzymes?
2 acetyl CoA are joined by thiolase to make acetoacetly CoA. Another Acetly CoA is added by HMG-synthase. HMG CoA is cleaved by HMG CoA lyase into Acetoacetate which spontaneously loses CO2 to make acetone or uses NADH to make 3-hydroxybutyrate (D-beta-) by use of 3-hydroxybutyrate dehydrogenase.
How are ketone bodies converted into acetyl CoA when delivered to target tissues?
3-Hydroxybutyrate to Acetoacetate by 3-hydroxybutyrate dehydrogenase. Acetoacetate to Acetoacetyl CoA by Succinyl CoA: acetoacetate CoA transferase (CoA from sucinyl CoA). Then acetoacetate cleaved by Thiolase into two acetyl CoA.
What is Ketoacidosis?
depression of blood pH by excessive ketone body production when starving or diabetes
What does ketone body formation compensate for?
Hypoglycemia. but high ketone body count also points to MCAD.
