Beta-Oxidation

Question 1

What does the following notation represent in relation to lipids: 18:1?

Answer 1

18 carbons with one double bond

Question 2

How is hormone sensitive lipase regulated?

Answer 2

Deactivated by Insulin, Activated by glucagon, epinephrine and norepinephrine

Question 3

How are fatty acids activated?

Answer 3

By linkage to CoASH catalyzed by Fatty acyl CoA synthetase. First link to AMP with PPi as product (use ATP)

Question 4

Where does B-oxidation occur?

Answer 4

In the Mitochondria Matrix

Question 5

How does palimtoylCoA cross the impermeable membrane into the matrix?

Answer 5

The carnitine shuttle

Question 6

How does the Carnitine Shuttle work?

Answer 6

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

Question 7

What is the major regulator of FA metabolism?

Answer 7

CPT I

Question 8

How is CPT I regulated?

Answer 8

Allosteric Inhibition by Malonyl-CoA. Acetyl CoA is converted to Malonyl CoA by ACC, and ACC is inhibited by AMP and activated by insulin

Question 9

What is the effect of CPT II deficiency?

Answer 9

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

Question 10

What happens in one cycle of B-ox.?

Answer 10

OHOC Ox., Hydration, Ox., Carbon bond cleavage

Question 11

What are the four main enzymes involved in B ox. in order and substrates?

Answer 11

Acyl-CoA Dehydrogenase (FAD-FADH2), Enoyl-CoA-Hydratase (H2O), Hydroxyacyl-CoA Dehydrogenase (NAD+-NADH), Thiolase (CoA-SH)

Question 12

How many ATP are made per cycle of B ox.?

Answer 12

14 ATP (but minus 2 ATP for Fatty acyl CoA synthetase)

Question 13

What is MCAD?

Answer 13

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

Question 14

How is MCAD diagnosed?

Answer 14

Lipid profile in the blood (lots of it)

identification of mutations in the ACDH gene

Question 15

What is the MCAD prognosis?

Answer 15

If caught before hypoglycemic episodes not bad. Improves with age

Question 16

What is Jamaican Vomiting sickness?

Answer 16

Similar to MCAD. Caused by toxin from the ackee fruit. Usually not fatal.

Question 17

What enzyme compensates for cis fatty acids/ wrong place for double bond?

Answer 17

Enoyl CoA Isomerase and 2,4-Dienoyl CoA reductase (second uses NADPH)

Question 18

What is more useful to the cell B ox. of unsaturated or saturated fats?

Answer 18

saturated. No extra enzymes.

Question 19

How are odd chain FAs taken care of and by what enzymes?

Answer 19

PropionylCoA is carboxylated (ATP and HCO3- used) by propionyl CoA carboxylase into methylmalonyl CoA and then made into succinyl CoA by methylmalonyl CoA mutase

Question 20

What are and where are VL chain FAs oxidized

Answer 20

<22C. Degraded by peroxisome

Question 21

How is VL ox. different than B ox.?

Answer 21

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

Question 22

Can humans produce branched chain FAs?

Answer 22

No. Plants only

Question 23

How and where are branched FAs oxidized?

Answer 23

They are broken down in the peroxisome like VL FAs but the first carbon is ox. to CO2 by alpha ox.

Question 24

What is omega-ox and where, how, and why does it take place?

Answer 24

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.

Question 25

What happens if glucose is used up and the liver’s storage of glycogen is depleted?

Answer 25

Keton bodies are formed to be used in the brain

Question 26

Name the three ketone bodies

Answer 26

3-Hydroxybutyrate, acetoacetate, and acetone.

Question 27

Where are ketone bodies formed?

Answer 27

The liver

Question 28

How does the body signal to make ketone bodies?

Answer 28

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

Question 29

How are ketone bodies synthesized? What enzymes?

Answer 29

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.

Question 30

How are ketone bodies converted into acetyl CoA when delivered to target tissues?

Answer 30

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.

Question 31

What is Ketoacidosis?

Answer 31

depression of blood pH by excessive ketone body production when starving or diabetes

Question 32

What does ketone body formation compensate for?

Answer 32

Hypoglycemia. but high ketone body count also points to MCAD.