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Advanced Biochemistry > Fatty Acid Oxidation (Catabolism) > Flashcards

Fatty Acid Oxidation (Catabolism) Flashcards

Lipid Metabolism: Chapter 20

1
Q

ß-Oxidation Hypothesis

A

ß-Oxidation Hypothesis

  • breakdown occurs at the C that is ß to the carboxyl group
  • fatty acid is progressively degraded by two carbon units
    • Aka. breaking down 2 C’s at a time
  • confirmed in the 1950’s
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2
Q

Why is the degradation of fatty acids called ß Oxidation?

A

Why is the degradation of fatty acids called ß Oxidation?

The degradation of fatty acids is called ß Oxidation b/c breakdown occurs at the C that is ß to the carboxyl group

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3
Q

Fatty Acid Activation

A

Fatty Acid Activation

Before the fatty acids can be oxidized, they must be activated with CoA. The reaction is catalyzed by Acyl-CoA synthetases:

Fatty Acid + CoA + ATP ⇔ fatty acyl-CoA + AMP + PPi

  • the reaction is catalyzed by acyl-CoA synthetases*
  • this is a two step mechanism*
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4
Q

Acyl-CoA Synthases

A

Acyl-CoA Synthases:

  • Catalyze the ATP-dependent transfer of a thiol group (CoA)
  • At least 3 different enzymes that differ in their chain-length specificity
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5
Q

Mechanism of Fatty Acid Activation

A
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6
Q

Describe the activation of fatty acids with CoA

A

Describe the activation of fatty acids with CoA

Before the fatty acids can be oxidized, they must be activated with CoA. The reaction is catalyzed by Acyl-CoA synthetases:

Fatty Acid + CoA + ATP ⇔ fatty acyl-CoA + AMP + PPi

  • catalyzed by acyl-CoA synthetases
    • which catalyze the ATP-dependent transfer of a thiol group (CoA)
  • ATP activates the fatty acid for reaction with thiol
  • pyrophosphate hydrolysis drives the reaction
  • Activation occurs in the cytosol
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7
Q

Fatty Acid Transport into the Mitochondrial Matrix

A

Fatty Acid Transport into the Mitochondrial Matrix

  • fatty acid oxidation occurs inside the mitochondrial matrix
  • fatty acids are transferred to carnitine
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8
Q

Carnitine

A

Carnitine

  • Carnitine carries acyl groups across mitochondrial membrane
    • the fatty acids are converted back to acyl-CoAs in the mitochondrion
    • Carnitine is returned to the cytosol
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9
Q

ß Oxidation of Fatty Acids to Acetyl-CoA

A

ß Oxidation of Fatty Acids to Acetyl-CoA

Four recurring reactions

  1. oxidation
  2. hydration
  3. oxidation
  4. thiolysis

Each recurrence:

  • shortens the chain by 2 C’s
  • produces Acetyl-CoA
    • which can make 1 GTP, 1 FADH2, & 3 NADH in the CAC
  • produces two reducing equivalents
    • FADH2 for the ET chain
    • NADH + H+
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10
Q

3 Names for the Citric Acid Cycle (CAC)

A

3 Names for the Citric Acid Cycle (CAC)

  1. Krebs Cycle
  2. Citric Acid Cycle (CAC)
  3. Tricarboxylic Acid Cycle (TCA cycle)
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11
Q

Overview of Catabolism (Stages)

A

Overview of Catabolism (Stages)

Stage 1: Energy stores are broken down into their building blocks

Stage 2: Building blocks are degraded to the common intermediate acetyl CoA

Stage 3: Energy Production Payoff

  • In the CAC, acetyl groups are oxidized to CO2, generating lots of e- in the form of NADH and FADH2
  • The e- are converted to ATP via the Electron Transport Chain (ETC) & oxidative phosphorylation
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12
Q

Where does Fatty Acid Activation occur?

A

Where does Fatty Acid Activation occur?

the cytosol

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13
Q

Where does ß Oxidation occur?

A

Where does ß Oxidation occur?

the mitochondria

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14
Q

Where does Fatty Acid Oxidation occur?

A

Where does Fatty Acid Oxidation occur?

the mitochondrial matrix

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15
Q

Yield of products per round of ß Oxidation

A

Yield of products per round of ß Oxidation

Fatty acid oxidation is highly exergonic

Yield Per Round :

of the 4 recurring reactions

Direct

w/Krebs Cycle

1 Acetyl-CoA

1 GTP (=ATP)

1 FADH2

3 NADH

1 FADH2

1 FADH2

1 NADH

1 NADH

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16
Q

How many ATP’s is FADH2 equivalent to? NADH?

A

How many ATP’s is FADH2 equivalent to? NADH?

1 FADH2 = 1.5 ATP

1 NADH = 2.5 ATP

17
Q

Oxidation of Unsaturated Fatty Acids requires _____________________________________

to create typical 𝛽 oxidation intermediates.

A

Oxidation of unsaturated fatty acids requires double bond isomerization & reduction to create typical 𝛽 oxidation intermediates

18
Q

The final round of 𝛽 oxidation of odd-chain fatty acids produces _______________ and _____________.

A

The final round of 𝛽 oxidation of odd-chain fatty acids produces 1 propionyl-CoA and acetyl-CoA

19
Q

What is the fate of propionyl-CoA and acetyl-CoA?

A

The fate of propionyl-CoA and acetyl-CoA:

final round of ß oxidation gives propionyl-CoA and acetyl-CoA rather than two molecules of acetyl-CoA.

Propionyl-CoA is oxidized to succinyl-CoA for entry into the CAC

20
Q

What reaction is catalyzed by methylmalonyl-CoA mutase ?

A

This reaction is involved in the pathway to convert propionyl-CoA to succinyl-CoA, which will ultimately be converted to acetyl-CoA for use in the Citric Acid Cycle

21
Q

What are the important metabolic function of ketone bodies?

A

Important metabolic function of ketone bodies

Ketone bodies are important metabolic fuels for peripheral tissues:

  • Heart
  • Skeletal muscle
  • Brain during starvation
22
Q

5 Differences between fatty acid ß oxidation and fatty acid biosynthesis

A

5 differences btwn Fatty Acid ß Oxidation & Biosynthesis

  1. Cellular location - synthesis takes place in the cytoplasm; degradation takes place in the mitochondrial matrix
  2. Acyl group carrier - intermediates in fatty acid synthesis are covalently linked to the sulfhydryl group of acyl carrier protein (ACP); breakdown intermediates are covalently linked to the sulfhydryl group of CoA
  3. Electron acceptor/donor - the reductant in fatty acid synthesis is NADPH; whereas the oxidants in fatty acid degradation are NAD+ and FAD
  4. Stereochemistry of the hydration/dehydration rxn
  5. The form in which C2 units are produced/donated - the growing chain is elongated by C2 units from malonyl-CoA (a C3 compound); Acetyl-CoA is the C2 product from oxidation
23
Q

What does the tricarboxylate transport system do?

A

The tricarboxylate transport system transfers acetyl-CoA into the cytosol for fatty acid synthesis

24
Q

What enzyme is involved in the formation of malonyl-CoA ?

A

Acetyl CoA-carboxylase (ACC) is the enzyme involved in the formation of malonyl-CoA

25
Q

When ATP demand is HIGH…

_____________________________________________

____________________________________

When ATP demand is LOW…

_____________________________________________

____________________________________

A

When ATP demand is HIGH…

acetyl-CoA is produced from fatty acids in the mitochondria and consumed to make ATP

When ATP demand is LOW…

acetyl-CoA must be transported to the cytosol…where it is converted to fat for storage

Advanced Biochemistry (5 decks)

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