new 5 fatty acid catabolism

8/13/2019 New 5 Fatty Acid Catabolism

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Fatty Acid Catabolism

A AngelesChem 40


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Digestion, Mobilization and Transport of FatsRefer to ourpreviousdiscussion


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About one third of our energy needs comes from

dietary triacylglycerols ~80% of energy needs of mammalian heart and liverare met by oxidation of FA


(chemically inert) and slow delivery

Fats are hydrolyzed into fatty acids and glycerol inthe cytoplasm

Energy derived from glycerol ~5%


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Glycerol can enter the glycolytic pathway

What happens to glycerol?

How many ATPs can we derive from1 mol of glycerol?


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Fat (fatty acid) catabolism provides:

1. Reducing equivalents that will ultimately produceATP2. Acetyl-CoA that can


be converted to ketone bodies (alternate fuel

source for brain and other tissues) in the liver be used for cholesterol biosynthesis act as a biosynthetic precursor


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-oxidation of fatty acids occurs in mitochondria Small (< 12 C) fatty acids diffuse freely across

mitochondrial membranes Larger fatty acids are transported via acyl-

Fatty Acid Transport to the Mitochondria

carn t ne carn t ne transporter


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Fatty Acid Transport to the Mitochondria1. Fatty acid activation in the cytosol

Fatty acid + CoA + ATP Fatty acyl-CoA + AMP + 2Pi

Favorable! G o=-34 kJ/mol


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2. Fatty acid transferto carnitine to formfatty-acyl carnitine

Fatty AcidTransport to the

Mitochondria

This FAsfate is

sealed.

3. Transport(facilitateddiffusion)

4. Removal of carnitinein the matrix


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Fatty Acid Transport to the Mitochondria


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Occurs in three stages consider the oxidation of

Oxidation of Fatty Acids

palmitate


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STEP 1:

Dehydrogenation ofFatty Acyl CoA

Formation of double

-oxidation of Fatty Acids

bond between

carbons (oxidation) Yields 1 FADH 2


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STEP 2:

Hydration of doublebond

-OH is added to the


carbon


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STEP 3:

Dehydrogenation at carbon

-OH carbonyl carbon


(oxidation) Yields 1 NADH Priming for nucleophilic

attack


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STEP 4:

Thiolysis Yields 1 acetyl CoA + acyl

CoA (n-2)



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Summary:

Every other carbon is converted to aC=O

Allows nucleophilic attack by CoA-SH


on remaining chain 1 CoA-SH is used for every 2 carbon

segment to release acetyl-CoA

Each round produces: 1 FADH2, 1NADH, 1 Acetyl-CoA (2 in the lastround)


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How many rounds of -

oxidation occurs for a FAwith even numberedcarbons?


(n/2)-1 rounds


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How many ATPs are formed in one complete

oxidation of stearic acid? Activation: -2 ATPs (the FA already has CoA, no

need to subtract)


8 rounds of -oxidation: 8(1 FADH 2 and 2 NADH) 9 Acetyl CoAs go into the TCA Answer: 120 ATPs Compare this energy yield with that of one

glucose molecule


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What happens if the FA is unsaturated?

Bypasses the initialdehydrogenation step Cis-isomer Trans-isomer

2 Subtract 1.5 ATPs per

unsaturation


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Most dietary fatty acids are even-numbered

Many plants and some marine organisms alsosynthesize odd-numbered fatty acids


- - -numbered fatty acids

Bacterial metabolism in the rumen of ruminants

also produces propionyl-CoA


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Subtract 6 ATPs in the last

TCA cycle

-oxidation of Fatty

Acids


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How many ATPs are formed in one complete

oxidation of pentadecanoic acid? Activation: -2 ATPs -


6 Acetyl CoAs go into the TCA 1 succinyl CoA goes into the TCA

Answer: 86 ATPs


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Can we live off fatty acids alone?

Entry of acetyl-CoA into citric acid cycle requiresoxaloacetate When oxaloacetate is depleted, acetyl-CoA is converted

Ketone Body Production

Production of ketone bodies increases duringstarvation

Ketone bodies are released by liver to bloodstream Organs other than liver can use ketone bodies as fuels


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Acetone can be exhaled

Acetoacetate and -hydroxybutyrate are transported inthe blood to other tissues

Ketone Body

Production

Too high levels of acetoacetate

and -hydroxybutyrate lower bloodpH dangerously (acidosis)

Accumulation of ketone bodies inthe bloodstream ketosis


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Synthesis

Fats are an important energy source in animals Two-carbon units in fatty acids are oxidized in a four-step -

oxidation process into acetyl-CoA


In the process, NADH and FADH 2 are formed willeventually be used in the ETC to produce ATP

Acetyl-CoA formed in the liver can be either oxidized via thecitric acid cycle or converted to ketone bodies that serve asfuels for other tissues

new 5 fatty acid catabolism

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