NBME - 6/24 - TBL Metabolism of MCAD Deficiency

Question 1

Why do we do Fatty Acid Metabolism?

Answer 1

Keeps you alive while you sleep without having to wake you up to eat!

Question 2

Fatty Acid enters your blood…then what

Answer 2

Picked up by Albumin, goes everywhere. Eventually it finds a mitochondrion, and goes in via the Carnitine Transport System.

Guess what the next question is…

Question 3

Outline the Carnitine Transport System

Answer 3

Fatty acid is hanging around outside the mitochondria, hits Acyl-CoA Synthase which is bound up in the membrane, turning it to FA-CoA, which now can diffuse through.

The membrane bound Carnitine transporter in the outer matrix pumps in Carnitine for CPT I to use. CPTI takes that FA-CoA and swaps the CoA for a Carnitine, making FA-carnitine, which can now diffuse into the inner membrane.

However, FA-Carnitine isn’t very useful. We use CPT II to turn FA-Carnitine back to FA-CoA, which can undergo beta oxidation

Question 4

How many ATP are used to turn FA to FA-CoA?

Answer 4

2 ATP

Question 5

What does a FA-Carnitine look like?

Answer 5

A FA bound to the middle of a carnitine which is a zwitter-ion

Question 6

Who gets MCADD and what does it look like clinically?

Answer 6

Presents in children < 2 y.o. as hypoketosis and hypoglycemia with an infection.

Can progress to them being comatose secondary to a bunch of Medium chain FAs in their brain

Question 7

Labs for MCADD

Answer 7

FA intermediates accumulating in the plasma and urine, which are dangerous because they are basically just free floating unesterified carboxyl groups.

C6:0

C8:0

C8:1, cis - delta 4

c8: 1, cis - delta 5
c10: 1, cis - delta 4 - PATHOGNOMONIC

Question 8

How do we break down VLCFA?

Answer 8

Trim it down to an MCFA in peroxisomes first, then send it to the mitochondria

Question 9

When do we use omega oxidation?

Answer 9

We do this in the smooth ER when beta oxidation is on the fritz, but it can only do 1 carbon at a time and generates C6-C8 dicarboxyllic acids, which is often an indicator for some disorder involving FA oxidation.

Question 10

FA nomenclature based on size

Answer 10

Carbons:

20+ = Very long chain

12 - 20 = Long chain

6 - 12 = MCFA

4 - 12 = MCADD related stuff

Less than 6 = Short chain

Question 11

First step of Beta oxidation!

Fatty Acyl CoA to:

Answer 11

Fatty Acyl CoA to trans fatty enoyl CoA via Acyl CoA dehydrogenase, which turns FAD to FADH2 (makes since, we gotta put those H’s somewhere)

1.5 ATP

Question 12

Second step of Beta Oxidation

Answer 12

Trans fatty enoyl CoA gets turned to L-B-Hydroxyacyl CoA via Enoyl CoA reductase (just need water for this step)

Question 13

Third step of Beta oxidation now that all the trans are gone.

Answer 13

L-B-Hydroxy acyl CoA gets turned to B-Ketoacyl CoA by B-Hydroxyacyl CoA dehydrogenase (Uses NAD+ to NADH, this should make since, we are trying to oxidize. Beta OXidation)

2.5 ATP

Question 14

Final step, what is our main goal?

Answer 14

B-Ketoacyl CoA gets broken up into something useful

Fatty Acyl CoA (2 carbons fewer)

and an Acetyl CoA

All thanks to B-Keto Thiolase

Question 15

What step of Beta Oxidation is messed up because of MCADD?

Answer 15

The first step.

Question 16

MCFAs build up where due to MCADD?

Answer 16

Mitochondria

Question 17

MCADD has something tightly bound to it, describe it

Answer 17

MCADD has tightly bound FAD to it. This mobile carrier, ETF (Electron Transfer Flavoprotien) transfers electrons from FAD to CoQ of the mitochondrial ETC.

Question 18

Why do kids have to be infected to get MCADD?

Answer 18

Think about it. Kids love to eat, and unless they are sick, they won’t voluntarily fast to trigger MCADD.

Question 19

It’s difficult to go over Beta oxidation of weird fatty acids, which was one of the quiz questions, but the NBME isn’t going to ask how many steps it takes. If they do, there really isn’t a quick way to do it, so don’t waste time just to sit there wondering if you missed a step. Pick C and drive on.

Answer 19

Happy studying guys.