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Medical Biochemistry > Topic 14: Lipolysis and FA Oxidation > Flashcards

Topic 14: Lipolysis and FA Oxidation Flashcards

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USMLE® Step 1 flashcards
1
Q

Where does DIETARY fat go first upon absorption?

A

General Circulation, bypassing Hepatic Portal via lymphatic circulation

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2
Q

Where do ketones come from?

A

Processing of FFAs in the liver

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3
Q

What happens to the glycerol upon lipolysis?

A

Glycerol via Glycerol Kinase –> G-3-P via G-3-PDH –> DHAP

DHAP can go to Gluconeogenesis (most likely since breaking down fats means you need energy)
OR
directly to the glycolytic pathway

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4
Q

What is Step 1 of FA Beta-Oxidation?

A

it must be ACTIVATED first with CoA via Acyl-CoA Synthetase

This was also seen in the enterocyte for reassembly of TAGs.

NOTE: ATP is used to generate pyrophosphate and POWER this irreversible reaction. (2 ATP Equivalents)

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5
Q

What is Step 2 of FA Beta-Oxidation?

A

Fatty Acyl-CoA is combined with CARNITINE via CPT-1 to form AcylCarnitine + free CoA.SH

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6
Q

What is Step 3 of FA Beta-Oxidation?

A

Acylcarnitine is exchanged for Carnitine via CAT (Carnitine Acylcarnitine Translocase) to enter the matrix

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7
Q

What is Step 4 of FA Beta-Oxidation?

A

Acylcarnitine via CPT-2 has CoA added and Carnitine removed –> Fatty Acyl-CoA + Carnitine

Note: Reverse action of CPT-1 in cytosol

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8
Q

Are there two separate, distinct pools of CoA in the cytosol and matrix?

A

Yup. They never cross the IMM and are two separate pools.

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9
Q

What is Step 5 of FA Beta-Oxidation? (Fatty Acyl-CoA has just entered mitochondria)

A

Fatty Acyl-CoA via Acyl-CoA Dehydrogenase –> Enoyl CoA

Generates FADH2

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10
Q

What is Step 6 of FA Beta-Oxidation?

A

Enoyl CoA via Crotonase has H2O added to beta carbon –> Beta-Hydroxy-Acyl-CoA

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11
Q

What is Step 7 of FA Beta-Oxidation?

A

Beta-OH-Acyl-CoA via a different Acyl-CoADH oxidizes to –> Beta-KetoAcyl CoA

Generates NADH

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12
Q

What is Step 8 of FA Beta-Oxidation?

A

beta-ketoAcyl CoA via Thiolase adds another CoA –> Acetyl CoA!! + Shorter Chain Fatty Acid (which goes back to the top, rinse and repeat)

Generates Acetyl CoA!

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13
Q

How many carbons are removed per each cycle through beta-oxidation?

A

2 carbons at a time

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14
Q

What is the exception to the beta-oxidation with regard to different length fatty acids?

A

Different Dehydrogenase enzyme to deal with the various lengths of FAs.

MCFA and SCFA can enter the mitochondria without needing to be activated in the cytosol first.

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15
Q

What is the effect of a double bond (unsaturation) on FA metabolism?

A

less 1.5 ATP – minimal effect

This is because the step making FADH2 is skipped.

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16
Q

How many ATP are generated from 16C Saturated FA?

A 
7 C-C Cycles (last cycle yields 2 acetyl-CoA)
7FADH2 (*1.5)= 10.5 ATP
7 NADH (*2.5) = 17.5 ATP
8 Acetyl CoA (*10) = 80 ATP
FA Activation = -2 ATP
Total = 106 ATP

Don’t forget the cost for activation and that the last cycle will yield two Acetyl CoA.

17
Q

How many ATP are generate from 16:2C unsaturated FA?

A

So 2 double bonds, all we have to do is skip the first step which is what yields FADH2.

7 C-C Cycles
5 FADH2 (*1.5) = 7.5 ATP
7 NADH (*2.5) = 17.5 ATP
8 Acetyl CoA (*10) = 80 ATP
FA Activation = -2 ATP
Total = 103 ATP

Again, don’t forget to count the cost of -2 ATP for activation.

18
Q

Why do ketones result from Beta-Oxidation?

A

Beta-Oxidation generates a plethora of Acetyl CoA, of which the liver only needed some. Backup causes them to go to the ketone pathway.

19
Q

What tissues can generate ketones?

A

mostly the Liver, but also the kidney

20
Q

What tissues can use Ketones as fuel?

A

Brain, Heart, Skeletal muscle

21
Q

What are the ketone bodies we talked about?

A

1) Acetoacetate
2) Acetone
3) Beta-Hydroxybutyrate (not strictly a ketone but whatevs)

22
Q

When would we see high levels of ketone bodies in the blood/urine?

A

Starvation!!
also, uncontrolled Diabetes mellitus – just like being starved all the time

Glucagon levels are UP UP UP - lipolysis increases

23
Q

Where do excess Acetyl-CoAs in the cytosol go to?

A

Cholesterol Synthesis

24
Q

Where do excess Acetyl CoAs in the mitochondria go?

A

ketone synthesis

25
Q

What is Step 1 of Ketone formation?

A

Acetyl-CoA + Acetyl-CoA via Acetyl-CoA Transferase –> Acetoacetyl-CoA plus free CoA

26
Q

What is Step 2 of Ketone formation?

A

Acetoacetyl-CoA + Acetyl-CoA via HMG-CoA Synthase –> Hydroxymethylglutaryl-CoA plus free CoA

27
Q

What is Step 3 of Ketone formation?

A

HMG-CoA via HMG-CoA Lyase removes Acetyl-CoA –> Acetoacetate!! BOOM ketone!

28
Q

Is there a Step after Acetoacetate formation?

A

Of course. Acetoacetate is converted to and back from Beta-Hydroxybutyrate based on the the concentrations of the two.

Also Acetoacetate spontaneously and irreversibly to degrades to CO2 and Acetone!!

29
Q

How can you tell an animal is ketotic without running bloodwork?

A

Smell their breath –> ACETONE!

Fruity or Flowery smell (I think it smells like gasoline)

30
Q

What is Peroxisomal Beta-Oxidation used for?

A

VLFCA - VERY Long Chain Fatty Acids

Broken down in similar fashion (2 C at a time) until short enough and dumped to cytosol for normal FA Beta-oxidation

31
Q

What are the end products of VLCFA Beta-Oxidation?

A

Acetyl CoA and MCFA (octanoic acid)

32
Q

When is peroxisomal beta-oxidation utilized?

A

Fasting, High-fat feedings, Thermoregulation (hibernators)

Pretty much when Fat is the ONLY energy source being used.

33
Q

How is Beta-Oxidation regulated?

A

CPT-1 is INHIBITED by Malonyl CoA (1st step of building fats)

HSL STIMULATED by: Glucagon, Epi, NorE, Thyroxine, ACTH, TSH, GH

HSL INHIBITED by: Insulin and Ketones

34
Q

What did Dr. Eng hint would be on the exam?

A

How to calculate ATP Yield from various length fatty acids.

Regulation of of Beta-oxidation via CPT-1 and HSL.

35
Q

What’s the advantage of brain and muscle being able to utilize ketone bodies for fuel?

A

Immediate fuel for the TCA Cycle (ketones can be directly broken down into 2 acetyl CoAs)

Reduces Acidic content of blood (ketones are acids)

36
Q

What enzyme do statins target to inhibit cholesterol synthesis?

A

HMG-CoA Reductase

Medical Biochemistry (26 decks)

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