Fat metabolism Flashcards

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1
Q

What are the three main categories that lipid use is defined?

A

1) Bilayer (phosphate bilayer)
2) Energy Stores
3) Intra and extra-cellular signalling

There are some others than are fat-soluble vitamins that have regulatory/ co-enzyme functions

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2
Q

How are lipids transported? Why?

A

Compartmentalised or transported in association with protein
-they are insoluble

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3
Q

What are fatty acids?

A

-carboxylic acids with long chain hydrocarbon side groups

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4
Q

Where can substantial amounts of free fatty acids be found?

A

Blood plasma

-transported on serum albumin to point of consumption

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5
Q

Where is the only place that can’t rely on fat metabolism?

A

The brain as the serum albumin can’t cross the cell membrane

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6
Q

What type of lipids are fats and oils of plants and animals?

A

Tricylglycerols

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7
Q

What types of fatty acids are attached to each carbon?

A

Carbon 1: Usually saturated
Carbon 2: Usually unsaturated
Carbon 3: Either

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8
Q

How is glycerol formed from triacyglycerols?

A

They are Eserified via their carboxyl groups which results in a loss of charge

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9
Q

What are adipocytes?

A

They are specialised molecules for the synthesis and storage of Triacyglycerols (TAG’s)

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10
Q

What is the fat content for normal humans?

A

21% for men

26% for women

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11
Q

Where is the fat stored in the body?

A

1) Adipocytes: - white adipose tissue, TAG’s coalesce to form oily droplets (bady’s main energy reserve)
2) Liver, but most is exported and packaged with other lipids & apoproteins to form VLDL (Very-Low-Density-Lipoproteins

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12
Q

When does the mobilisation of fat occur?

A

Occurs during times of metabolic need which is initiated by hormone-sensitive lipase

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13
Q

What does hormone-sensitive lipase do?

A

Removes the fatty acid from C-1 and/or C-3 leaving a lipid with only 1 or 2 hydrocarbon chains
-the remaining chains are removed by diacylglycerol (if 2 chainz present) or monoacylglycerol (if 1 chain is present)

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14
Q

When is hormone-sensitive lipase activated?

A
  • When phosphorylated by a cyclic AMP (cAMP)

- when glucagon/epinephrine binds to cells

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15
Q

What is beta oxidation?

A

A series of catalysed reactions progressively degrading fatty acids by removing 2 Carbon units & involves the oxidation of the Beta Carbon atom to the carboxyl group

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16
Q

Where does beta oxidation take place and what does it produce?

A

Located in mitochondria

Produces AcetylCoA, NADH & FADH2

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17
Q

What occurs after Long Chain Fatty Acids (LCFA’s) enter the cell?

A
  • Converted in the cytosol to its CoA derivative (known as priming)
  • Catalysed by Long-Chain fatty acetyl-CoA synthatases known as Thiokinases
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18
Q

What is the reaction driven by?

A

Exergonic hydrolysis of pyrophosphate

19
Q

How are acyl-CoA’s transported across an impermeable mitochondrial membrane?

A
  • Carnitine Shuttle

- fatty acids transfer its acyl part on to carnitine forming acylcarnitine

20
Q

How does acylcarnitine tranported into matrix?

A

Exchanged with free carnitine in opposite direction by Carnitine palmitoyltransferase I (CPT-1)

21
Q

How is carnitine obtained?

A

In the diet from meat

-synthesised from lysine and methionine by liver and kidneys

22
Q

How can carnitine deficiencies arise?

A

1) Liver disease
2) Malnutrition/Vegetarian diets
3) Pregnancy or Burns victims which require increased carnitine
4) Haemodialysis

23
Q

How do short&medium fatty acids enter the mitochondria?

A

Chains with less than 12 carbons can enter without the carnitine shuttle and is not dependent on CPT-1

24
Q

What are the reactions of the Fatty acyl-CoA sequence?

A

1) Formation of a trans-a, beta double bond
- Caused by dehydrogenation and produces FADH2

2) Hydration of the double bond to form 3-L-hydroxyacyl-CoA

3) NAD+ dependent dehydrogenation of the beta-hydroxyacyl-CoA
- forms beta-ketoacyl-CoA and NADH

4) alpha Carbon - beta Carbon cleavage in a thiolysis reaction to form Actyl-CoA and a new acyl-CoA

25
Q

What is acetyl-CoA useful for?

A

Links fatty acid oxidation reactions & gluconeogenesis

26
Q

How many times are the beta oxidation reactions carried out per fatty acid?

A

(n/2)-1 times where n= carbon number which must be even

27
Q

What does each cycle produce?

A
  • an acetyl group
  • 1 NADH
  • 1 FADH2
28
Q

What happens to FADH2 after beta oxidation?

A

reoxidised by the mitochondrial electron-transport chain to reduce CoQ

29
Q

What is MCAD deficiency?

A

Medium-Chain Fatty Acyl CoA dehydrogenase deficiency

  • autosomal recessive disorder
  • decreased ability to oxidise fatty acids with 6 to 10 C
  • Severe hypoglycemia due to increased glucose reliance

-Cause of 10% of Sudden Infant Death Syndrome due to human milk being that length

30
Q

What is the ATP output for each fatty acid?

A
  • highly exergonic
  • each FADH2 provides 2ATP
  • each NADH provides 3ATP
  • each Acetyl CoA provides 12 ATP in the TCA cycle

Take away 2ATP from total due to it being used in fatty acyl-CoA formation

So a 16C acid produces 129ATP

31
Q

What are Ketone bodies?

A

Important energy sources in heart & skeletal muscle

  • are soluble so no need for lipoproteins or albumin
  • produced when acetyl-CoA exceeds oxidative capacity
  • Used in proportion to blood by extrahepatic (outside the liver) tissues
32
Q

Examples of ketone bodies?

A
  • Acetoacetate
  • 3-hydroxybutyrate
  • Acetone
33
Q

How is acetyl CoA produced?

A

the oxidative carboxylation of pyruvate by pyruvate dehydrogenase

34
Q

What is the ‘Tricarboxylate Transport System’ (TCA Cycle)?

A

1) Oxoloacetate is reduced to malate by malate dehydrogenase
2) Malate is oxidatively decarboxylated to pyruvate by malic enzyme

NOT COMPLETED QUESTION CARD

35
Q

How isthe carboxylation of Acetyl-CoA to Malonyl CoA achieved?

A
  • Catalysed by Acetyl CoA Carboxylase
  • Addition of CO2 through breakdown of ATP to release energy for reaction
  • Biotin is the coenzyme
36
Q

How is palmitic acid formed? first 4 reactions

A

1) Acetate is transferred from acetyl CoA to the -SH group of ACP
2) The 2C unit is transferred to the thiol group of a cysteine residue
3) The ACP accepts a 3C malonate unit from malonyl CoA
4) The acetyl group on the cysteine residue condenses with the malonyl group on ACP - CO2 is released and the loss of free energy drives the reaction

37
Q

How is palmitic acid formed? Steps 5,6,7

A

5) The keto group is reduced to an alcohol
6) A molecule of water is removed to introduce a double bond between carbons 2&3
7) The double bond is reduced

38
Q

What is the final stoichiometry of the formation of palmitate

A

8Acetyl-CoA + 14NADPH + 7ATP = Palmitate + 14NADP + 8CoA + 6H2O + 7ADP + 7Pi

39
Q

What is the structure of palmitate?

A

16Carbon fully saturated

40
Q

How can Palmitate be further elongates and where?

A

Elongated in the Smooth Endoplasmic reticulum (SER) or mitochondria onlt 2C added

-SER uses elongase system where Malonyl-CoA is the 2C donor and NADPH supplies the electrons

41
Q

How are fatty acids desaturated?

A

Desaturases are present in SER and will de-saturate long-chain fatty acids by adding double bonds

42
Q

How are certain polyunsaturated fatty acids obtained?

A

In the diet through red meats predominantly

43
Q

How are fatty acids regulated?

A

Insulin and Glucagon regulate the opposing lipid pathways