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MCD: metabolism > Lipids > Flashcards

Lipids Flashcards

1
Q

3 sources of fats

A

Diet
De novo biosynthesis in the liver - (starting from new in the liver)
Adipocyte stores - they can be hydrolysed to give free fatty acids and glycerol

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2
Q

Describe the process of lipid digestion

A
  • there is a mix of free fatty acids, mono and diacylglycerols that are solubilised
  • These then get taken up by the enterocytes within the intestine
  • The lipid digestion by lipases form monoacylglycerols (MAG), diacylglycerols (DAG) and free fatty acids (FAs) which join Bile Salts, Cholesterol, Lysophosphatidic Acid and fat soluble vitamins to form mixed micelles.
  • the mixed micelles are absorbed by enterocytes
  • Triacylglycerols (TAGs) are resynthesised
  • TAGs are packaged into chylomicrons which then enter the lymphatic system and join the circulatory system
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3
Q

Describe beta oxidation

A
  • Fatty acid -> acyl coA using 2 ATPs in outer mitochondrial membrane
    enzyme = acyl CoA synthethase
  • the Acyl CoA enters the mitochondria from the outer mitochondrial membrane by carnitine shuttle
  • Fatty acyl coA oxidised and FAD is reduced to FADH2
  • the molecule produced is then hydrolysed
  • the product is then oxidised so NAD+ –> NADH
  • remove a molecule of acetyl coA by bringing in a molecule of CoA using beta- ketothiolase
  • The remaining part of fatty acyl CoA which has been shortened by two carbons then repeats the cycle

overall the original fatty acyl CoA has been shortened by 2 carbons

  • during each cycle 1 NADH and 1FADH2 are formed
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4
Q

Overall equation for breakdown of palmitate

A

Palmitoyl coA + 7FAD + 7 NAD+ + 7H20 + 7CoA ——> 8 acetyl coA + 7 FADH2 + 7 NADH

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5
Q

When can acetyl coA from beta oxidation enter TCA?

A

When beta oxidation and carbohydrate metabolism are balanced as oxaloacetate is needed

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6
Q

Which 2 enzymes are involved in biosynthesis of lipids?

A

Acetyl coA carboxylase

Fatty acid synthase

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7
Q

What happens if acetyl coA can’t enter TCA?

A

Produces:
Acetoacetate
D 3 hydroxybutyrate
Acetone

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8
Q

Describe lipogenesis

A

Acetyl coA + HCO3 = malonyl coA using acetyl coA carboxylase
Transfer malonyl to ACP = malonyl ACP using malonyl-coA-ACP transferase
Transfer acetyl from acetyl coA to ACP = acetyl ACP using acetyl-coA-ACP transferase
Condensation of acetyl ACP and malonyl ACP = acetoacyl ACP
Reduction using ketoreductase
Dehydration using dehydratase
Reduction using Ebola reductase

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9
Q

Differences between fat metabolism and synthesis

A 
Synthesis = ACP and uses NADP as reducing agent, happens in ER and mitochondria 
Metabolism = coA and uses NAD+ and FAD as reducing agents , happens in mitochondria
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10
Q

Lipogenesis equation

A

Acetyl coA + 7 malonyl coA + 14 NADP + 14H+ = palmitate + CO2 +6H2O + 8 coA + 14 NADP+

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11
Q

Diseases to do with lipid metabolism

A 
Medium chain acyl coA dehydrogenase deficiency (MCADD) 
- autosomal recessive 
- part of heel prick test
-  no fasting
- have a high carb diet 
Primary carnitine deficiency
- autosomal recessive
- carnitine supplements given
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12
Q

what are saturated fatty acids like?

A
  • they are completely saturated with hydrogen (there are no double bonds) they are straight
  • solids
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13
Q

what are unsaturated fatty acids like?

A
  • they have double bonds which inhibit rotation, therefore, there are kinks in the chain
  • these are liquids
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14
Q

what are adipocytes?

A

in mammals specialised cells called adipocytes take on the role of fatty acid storage

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15
Q

how does bile emulsify fats?

A
  • bile salts are generated by the liver and stored in the gall bladder
  • during digestion they are secreted into the intestine
  • They emulsify fats and aid their absorption
  • biles convert fats into a soluble form so that the lipases can start breaking them down
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16
Q

what does a lack of bile salts cause?

A
  • Lack of bile salts causes fats to pass through the digestive tract undigested and unabsorbed resulting in steatorrhea (fatty stool)
17
Q

what is the structure of bile and how does that relate to how bile works?

A
  • bile salts have a hydrophobic face and hydrophilic face which allows the bile salts to interact with solute and triacylglyerols
  • Bile salts present the hydrophobic face to the triacylglycerols and the hydrophilic face to the solvent.
18
Q

what is a mixed micelle?

A

A Mixed Micelle forms which is a mixture of triacyl-, diacyl-, monoacylglycerols and free fatty acids.

19
Q

why is having anhydrous food supplies needed?

A
  • good way of keeping compact food stores for subsequent mobilisation when needed
  • if stored as glycogen people would be much heavier as glycogen needs water to be soluble
  • every gram of glycogen needs 2 grams of water
20
Q

what is orlistat?

A

reduces fat absorption by 30% which is almost completely excreted by the faecal route - treats obesity.

21
Q

compare caloric yield of fatty acids and carbohydrates?

A
  • The caloric yield of fatty acids is about double that of carbohydrates
  • More than half the body’s energy needs (including the liver but NOT the brain) comes from the oxidation of fatty acids.
22
Q

how can acetyl CoA enter the TCA cycle?

A
  • can only enter is beta oxidation and carbohydrate metabolism are balanced
  • this is because oxaloacetate is needed for entry of acetyl CoA into the TCA cycle
23
Q

what happens is fat breakdown predominates carbohydrate metabolism?

A

If fat breakdown predominates (e.g. when fasting/starving), acetyl CoA forms:
• Acetoacetate
• D-3-hydroxybutyrate
• Acetone

24
Q

how many of what kind of bond generate the Acyl CoA from the fatty acid?

A

2 phosphoanhydride bonds

this is the same as ATP

these are needed to start off the reaction

25
Q

how does the Carnitine Shuttle

work?

A
  • the species is firstly coupled to a molecule of carnitine (catalyst = Carnitine Acyltransferase I) to form Acyl Carnitine
  • Acyl Carnitine is then transported across the membrane by a translocase
  • Carnitine Acyltransferase II then removes the acyl group from acyl carnitine and passes it on to CoA to form Acyl CoA and reform carnitine.
  • The carnitine is moved back across the membrane to the cytoplasmic side by a translocase to pick up more Acyl CoA
26
Q

net ATP production of palmitate B oxidation?

A

You get far more ATP from fatty acids compared to from glucose metabolism

27
Q

what enzymes does fatty aid biosynthesis involve?

A
  • Acetyl CoA Carboxylase

- Fatty Acid Synthase (FAS)

28
Q

how are fatty acids formed?

A

decarboxylative condensation reactions involving the molecules Acetyl-CoA and Malonyl-CoA.

29
Q

what does the fatty acid undergo after elongation?

A
  • the fatty acid undergoes reduction and dehydration
    Ketoreducatase (KR)
    Dehydratase (DH)
    Enol Reductase (ER
30
Q

what is the lipogenesis process?

A
  • first acetyl CoA is converted to malonyl CoA using the enzyme Acetyl CoA carboxylase
  • malonyl is transferred from malonyl CoA to the Acyl carrier protein to make malonyl - ACP.
  • Transfer of acetyl from a CoA species to acyl carrier protien (ACP) to form Acetyl-ACP (catalysed by Acetyl-CoA-ACP Transferase)
31
Q

what happens to the acetyl ACP?

A
  • acetyl ACP is condensed with malonyl ACP to make 4C species acetoacyl - ACP
32
Q

what are the differences between fatty acid synthesis and fatty acid degredation?

A

Differences:
• Carriers: CoA v ACP
• Reducing Power: FAD/NAD+ v NADPH

33
Q

what are Acyl-CoA Dehydrogenases ?

A
  • family of enzymes - there are different types of enzymes for the different lengths of fatty acid chain.
  • 5 types: 3-hydroxy, Short, Medium, Long, Very Long
34
Q

what is MCADD?

A
  • Autosomal Recessive - occurs predominantly in caucasians.
  • 1/ 10,000
  • accounts for 1/100 sudden infant death
  • If diagnosed - avoid fasting and have a rich carbohydrate diet
  • part of heel prick test
  • patients must make sure thir body is not dependent upon fatty acids for energy
35
Q

what is a primary carnitine deficiency?

A
  • Autosomal recessive
  • Carnitine is needed to chaperone the Acyl group into the mitochondrial matrix from the outer membrane of the mitochondrion.
  • Carnitine can be given as a supplement to treat this deficiency.

MCD: metabolism (9 decks)

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