Fatty acid metabolism Flashcards

1
Q

What is the importance of fatty acids?

A
  • used for fuel
  • building blocks - cell walls
  • synthesis of glycerophospholipids, steroids and lipid-based hormones
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2
Q

What are fatty acids stored as?

A

triacylglycerols

- in the cytoplasm of adipocyte cells

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3
Q

Compare the energy/ATP yield of triacylglycerols (TAGS) to that of glycogen.

A

1g of TAG stores 6 X more energy than 1g of glycogen

  • beta-oxidation of hexadecanoic acid yields 106 molecules of ATP
  • aerobic respiration of glucose yields 32 molecules of ATP
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4
Q

What releases fatty acids from triglycerides?

A

Lipases

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5
Q

How do you activate the fatty acids?

A
  • formation of a thioester linkage to CoA to form an acyl CoA
  • acyl CoA is then oxidised
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6
Q

How do the fatty acyl-CoA’s get transported into the inner mitochondrial membrane?

A
  • if it is C8 and lower acyl-CoA, it can diffuse across the inner mitochondrial membrane
  • if it is C10 and greater acyl-CoA, this will be actively transported via conjugation to carnitine to form an acyl carnitine through the carnitine shuttle system. This is then transferred back to CoA prior to beta-oxidation
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7
Q

Where does fatty acid beta-oxidation occur?

A

mitochondrial matrix and peroxisome

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8
Q

What are the steps in fatty acid beta-oxidation?

A
  1. oxidation
  2. hydration
  3. oxidation
  4. thiolysis
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9
Q

What does fatty acid beta-oxidation produce?

A

an acetyl CoA and an acyl CoA

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10
Q

What happens in step 1 of fatty acid beta-oxidation?

A
  1. Acyl CoA is oxidised by acyl-CoA DH, introducing a double bond in the 2-3 positions
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11
Q

What happens in step 2 of fatty acid beta-oxidation?

A
  1. hydration of the double bond to form a 3-hydroxyacyl-CoA

- enzyme: enoyl CoA hydratase

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12
Q

What happens in step 3 of fatty acid beta-oxidation?

A
  1. oxidation of the 3-hydoxyacyl-CoA to form 3-ketoacyl-CoA

- enzyme: 3-hydroxyacyl-CoA DH

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13
Q

What happens in step 4 of fatty acid beta-oxidation?

A
  1. cleavage of 3-ketoacyl-CoA to produce acetyl CoA and an acyl CoA
    - cleavage at the 2 & 3 position
    - enzyme: β-ketothiolase
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14
Q

What happens during the beta-oxidation of monounsaturated fatty acids?

A
  • do cycles of beta-oxidation till the double bond is close to the carbonyl
  • then use enzyme cis-Δ3-enoyl isomerase to convert a C3-C4 double bond to a C2-C3 double bond required for the next steps of the oxidation
  • an enoyl CoA will be produced
  • can undergo Step 2 of fatty acid beta oxidation
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15
Q

What happens during the beta-oxidation of polyunsaturated fatty acids?

A
  • do cycles of beta-oxidation till one of the double bonds is close to the carbonyl
  • then use enzyme cis-Δ3-enoyl isomerase to convert a C3-C4 double bond to a C2-C3 double bond required for the next steps of the oxidation
  • go another round of beta oxidation (gets rid of first double bond)
  • do STEP 1 again, and oxidise to form another double bond in the 2-3 position
  • use a reductase to convert both double bonds into a single 3-4 double bond (so only 1 double bond now present)
  • then use isomerase to convert a C3-C4 double bond to a C2-C3 double bond required for STEP 2 of fatty acid oxidation
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16
Q

What are the products formed after an odd-chain fatty acid beta oxidation? (C5 fatty acid for e.g)

A
  • will produce acetyl-CoA and propionyl CoA in the final cycle
  • the propionyl CoA can then enter the TCA cycle
17
Q

Why is beta-oxidation done in the peroxisome?

A

to shorten long-chain fatty acids for easier transport in to mitochondria
- very long chain fatty acids are not easily transported by carnitine shuttle

18
Q

What is the major difference between beta-oxidation that happens in the mitochondria vs peroxisome?

A
  • in the first oxidation step
  • in mitochondria e- are transferred to FADH2 and used in the et chain
  • in peroxisomes, e- are passed to FADH2 who transfer to form hydrogen peroxide
  • H2O2 is converted to H2O and O2 by a catalase enzyme in the peroxisome
  • no ATP produced
19
Q

What is medium chain acyl CoA dehydrogenase (MCAD) deficiency?

A
  • fatty acid oxidation disorder
  • autosomal recessive disorder
  • symptoms seen in early childhood, generally after fasting or illness
  • symptoms: seizures, come and hypoglycaemia
  • can be detected with dried blood spot analysis during newborn screening
  • treated by avoiding long periods of fasting
20
Q

Where does fatty acid beta-oxidation usually occur?

A

in the liver