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Bioenergetics And Transformation > Fatty Acid Metabolism > Flashcards

Fatty Acid Metabolism Flashcards

1
Q

Why do we store fat ?

A
  • one of the main energy stores
  • reduced and non polar : has a low osmotic pull and so there is little water associated with it giving it a small storage volume
  • high energy yield : 2.5x more than carbohydrates and proteins
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2
Q

Describe the different uses of fat for the body

A
  • needed for lipid synthesis by the body
  • lipids are important signalling molecules
  • lipids are needed for the storage of fat soluble vitamins
  • lipids are important for the calcification of dentine
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3
Q

What are the 2 types of fat storage tissues ?

A
  • white fat (adipose tissue)
  • brown fat
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4
Q

Describe white fat

A
  • TAG is sequestered in cells
  • it is a storage organ
  • clustered in certain locations
  • if it is stored in ectopic locations it is called visceral fat and this increases the risk of type 2 diabetes
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5
Q

Describe brown fat

A
  • it is found close to the heart
  • contains TAG and mitochondria
  • it is an active metabolic organ involved in heat generation
  • found in infants and hibernating animals
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6
Q

Where does the digestion and absorption of dietary lipids take place ?

A

Most digestion and absorption takes place in the small intestine

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7
Q

Briefly describe how lipids are digested

A
  • pancreatic lipases break the ester bonds to yield free fatty acids and mono acyl glycerides
  • bile salts aid digestion by creating an emulsion
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8
Q

How are short chain fatty acids absorbed ?

A

Short chain fatty acids which are less than 12C can enter the blood stream directly

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9
Q

Describe how longer chain fatty acids are digested and absorbed

A

1) longer chain fatty acids are resynthesized into triacylglycerides in the endoplasmic reticulum of mucosal cells
2) TAGs are then packaged into lipoprotein transport particles known as chylomicrons
3) chylomicrons are released into the lymph before entering the blood stream
4) they then travel to adipose tissue for storage
5) chylomicron remnants travel to the liver for processing

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10
Q

Describe the utilisation of fatty acids as fuels

A

this is a 3 stage process :
1) mobilisation of lipids to fatty acids and glycerol in fat cells prior to transportation to energy requiring tissues - lipolysis
2) activation of the fatty acids and transport to mitochondria in the energy requiring tissues
3) stepwise processing into acetyl CoA prior to degradation in central metabolism

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11
Q

Describe lipolysis (stage 1)

A

1) perilipin which is a protein found on the outside of lipid droplets is activated by phosphorylation by protein kinase A and this changes the conformation of the proteins so the enzyme hormone sensitive lipase moves closer to the lipid droplet
2) hormone sensitive lipase will recognise signals when fats are being released from their stores
3) glucagon will send a signal cascade
4) this activates cyclic AMP which activates protein kinase A
5) hormone sensitive lipase will then release fatty acids and glycerol from the fat droplet
6) glycerol can enter the bloodstream and serum albumen will transport fatty acids to the tissues

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12
Q

What stimulates and inhibits lipolysis ?

A

stimulated by :
- adrenaline
- noradrenaline
- glucagon
- ACTH (pituitary hormone)

inhibited by :
- insulin

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13
Q

Describe activation and transport (stage 2)

A

step 1 :
- activation occurs by the synthesis of Acyl CoA
- this requires an input of energy
- requires coenzyme A
- mediated by Acyl CoA synthetase

step 2 :
- carnitine will allow the fatty acids to enter the mitochondria from the cytosol
- it is a small molecule located in the inner mitochondrial membrane
- it is primarily used for transportation of long chain Acyl CoA molecules

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14
Q

Where are fatty acids broken down ?

A

in the mitochondria

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15
Q

Describe the beta oxidation pathway (stage 3)

A
  • saturated acyl CoA is degraded sequentially by the beta oxidation pathway (this means 2C are lost per round)
  • each round produces :
  • FADH2 = 1.5 ATP
  • NADH = 2.5 ATP
  • Acetyl CoA = 10 ATP
  • an acyl CoA which is 16C in length would yield 108 molecules of ATP (8 Acetyl CoA + 7 FADH2 + 7NADH)
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16
Q

How are fatty acids with an odd number of carbons metabolised ?

A
  • beta oxidation leaves propioyl CoA (3C)
  • propionyl CoA carboxylase converts this via methylmalonyl CoA to succinyl CoA which feeds into the citric acid cycle
17
Q

How are unsaturated fatty acids metabolised ?

A
  • may have a double bond in the β-γ position which would prevent them from entering the beta oxidation pathway
  • isomerase enzyme will shift the double bond to α-β
18
Q

Describe ketone body formation

A
  • Acetyl CoA enters the citric acid cycle if fat and carbohydrate metabolism is balanced
  • the entry is dependent on availability of oxaloacetate
  • during fasting and starvation oxaloacetate is consumed t form glucose so it is unavailable for condensation with Acetyl CoA
  • this leads to a lack of coenzyme A for fatty acid degradation
  • so Acetyl CoA is diverted to form ketone bodies
19
Q

Where does ketone body formation take place ?

A

ketone bodies are generated in the liver

20
Q

Where is the CoA transferase enzyme found ?

A

it is found in all body tissues but not the liver

21
Q

Summarise fatty acid synthesis

A
  • excess amino acids and carbohydrates are degraded
  • krebs cycle intermediates are produced
  • storage molecules e.g. glycogen and fats are synthesised
22
Q

How are fats stored ?

A
  • fatty acids are stored in the body as triacylglycerols
  • 3 fatty acid chains and glycerol are synthesised in the liver
  • they are transported to the adipose tissue as VLDL
  • they are stored in the adipose tissue until the body needs extra energy reserves and then they are stored as LDL
23
Q

Give an overview of fatty acid synthesis

A
  • acetyl coenzyme A is the building block of fatty acids
  • NADPH is the source of reducing potential
  • all fatty acids are derived from modifying palmitate (16C)
  • it is an energy requiring process

8 Acetyl CoA + 7 ATP + 14 NADPH > Palmitate + 7 ADP + 7 Pi + 14 NADP+ + 8 CoA

24
Q

How does Acetyl CoA cross the mitochondrial barrier ?

A
  • mitochondrial membrane is impermeable to acetyl coenzyme A and so it is converted into citrate and there is a special citrate transporter
  • acetyl CoA is formed inside the mitochondrial matrix
  • fatty acid synthesis occurs inside the cytosol
25
Q

What is the key regulatory enzyme of fatty acid synthesis ?

A

Acetyl CoA carboxylase

26
Q

Describe Acetyl CoA carboxylase

A
  • regulated by covalent modification and allosteric regulation
  • coverts acetyl CoA to malonyl CoA
  • it is a 2 stage reaction
  • requires ATP and biotin as a cofactor
27
Q

Describe the regulation of Acetyl CoA carboxylase

A
  • irreversible step to fatty acid synthesis
  • activity is increased by carbohydrate feeding
  • stimulated by insulin
  • inhibited by glucagon and adrenaline
  • stimulated by citrate and inhibited by palmitoyl CoA (allosteric regulation)
28
Q

What is the role of fatty acid synthase ?

A

it is an enzyme complex of 6 enzymes which catalyses the remaining reactions of fatty acid synthesis

29
Q

Describe the acyl carrier protein (ACP)

A
  • part of the fatty acid synthase enzyme
  • contains a phosphopantetheine prosthetic group
  • it is a long flexible carrier
  • has a cysteamine tail which forms thioesters with Acetyl CoA or Malonyl CoA
30
Q

Describe desaturation and elongation of fatty acids

A
  • other fatty acids are synthesised from palmitate
  • chain elongation occurs by adding 2C units at a time usually in the endoplasmic reticulum
  • desaturation occurs using oxygen as the oxidant and requires NADH
  • occurs in the endoplasmic reticulum
31
Q

Describe polyunsaturated fatty acids

A
  • some polyunsaturated fatty acids are nutritionally essential
  • dietary deficiency is characterised by dermatitis and poor wound healing
  • babies must not be fed low fat milk
32
Q

How is the reducing potential generated ?

A
  • 2 molecules of NADPH are required for each 2C subunit extension of the fatty acid chain
  • 1 NADPH is generated during export of acetyl CoA from the mitochondrion
  • other NADPH is generated by the PPP
33
Q

Describe differences between beta oxidation and fatty acid synthesis

A
  • located in the mitochondrion v cytosol
  • acyl carrier is CoA v ACP
  • C2 unit acceptor is CoA v C2 donor is malonyl CoA
  • electron acceptors are NAD+ and FAD v electron donor is NADPH
  • separate enzymes v multienzyme complex

Bioenergetics And Transformation (10 decks)

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