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PoM Block 1 > Cellular Metabolism 2- Lipids (2) > Flashcards

Cellular Metabolism 2- Lipids (2) Flashcards

1
Q

Where is acetyl coA generated by fatty acids?

A

in mitochondria

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2
Q

What are the 3 primary sources of fat?

A
  • diet
  • liver de novo biosynthesis
  • storage deposits in adipose tissue
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3
Q

What is the result of a lack of bile salts?

A

majority of fat passes through gut undigested and unabsorbed, resulting in steatorrhea (fatty stool)

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4
Q

What is Orlistat (tetrahydrolipstatin)?

A
  • potent inhibitor of gastric and pancreatic lipases
  • reduces fat absorption by 30%- excreted by faecal route
  • treatment for obesity, but causes abdominal pain, urgency to defecate, flatus and steatorrhea
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5
Q

How are lipids transported in the plasma?

A

by lipoproteins- contain fatty acids w/in a core- soluble hydrophilic outer

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6
Q

Where are chylomicrons produced and what is their role?

A
  • intestines

- dietary fat transport

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7
Q

Where are VLDLs produced and what is their role?

A
  • liver

- endogenous (originated in liver) fat transport

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8
Q

Where are IDLs produced and what is their role?

A
  • originate from VLDLs

- LDL precursor

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9
Q

Where are LDLs produced and what is their role?

A
  • originate from IDLs

- cholesterol transport

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10
Q

Where are HDLs produced and what is their role?

A
  • liver

- reverse cholesterol transport

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11
Q

What is the structure of a chylomicron?

A
  • phospholipid monolayer
  • apoproteins sat in layer
  • triglycerides inside
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12
Q

What is lipoprotein lipase and what is its function?

A
  • located on capillary endothelial cells lining adipose, heart and skeletal muscle tissues
  • recognises apoprotein–> activates enzyme (conformational change)
  • -> digests triglycerides and takes up fatty acids into cell (leaves glycerol in bloodstream)
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13
Q

What is the life cycle of chylomicrons?

A
  • enterocytes make chylomicrons containing lipids
  • HDL transfers apoproteins onto chylomicrons
  • can be recognised by tissues and deliver FFAs
  • then chylomicron remnants can get more apoproteins from HDL–> recognised by liver and taken up, reprocessed
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14
Q

What is the structure of a lipoprotein?

A
  • phospholipid monolayer containing cholesterol and apoproteins
  • surround a core of cholesterol esters and triglycerides
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15
Q

How are cholesterol esters made?

A
  • synthesised in plasma
  • cholesterol + phosphatidylcholine (donates acyl chain)
  • catalysed by LCAT (lecithin:cholesterol acyltransferase)
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16
Q

What is the life cycle of VLDLs, IDLs, HDL, and LDLs?

A
  • liver produces VLDLs- deliver contents to tissues
  • becomes lipid-depleted remnant
  • transfer of proteins from VLDL back to HDL
  • becomes IDL
  • cholesterol esters from HDL packaged and transferred to IDL
  • becomes LDL–> uptake by liver or macrophages
    (N.B. VLDL and HDL are the only ones synthesised by liver)
17
Q

Why are HDLs often referred to as ‘good cholesterol’?

A
  • they take cholesterol from peripheral tissues (dead or dying cells) back to liver for use or disposal by reverse cholesterol transport
  • thus they help to lower total serum cholesterol
18
Q

Why are LDLs often referred to as ‘bad cholesterol’?

A
  • raised LDL levels leads to atherosclerosis
  • transport cholesterol synthesised in liver to peripheral tissues w/ more than 40% of their weight being cholesterol esters
19
Q

How does the carnitine shuttle work?

A
  • generation of Acyl CoA species on cytoplasmic side
  • carnitine acyltransferase 1 transfers acyl group from acyl coA to carnitine–> acyl carnitine
  • acyl carnitine carried by translocase into mitochondrial matrix
  • reverse reaction using carnitine acyltransferase 2 to produce acyl coA and carnitine- which is shuttled back out
20
Q

How many beta oxidation reactions would be needed to generate 8 acetyl coA from palmitic acid (16C)?

A

7 rounds of beta oxidation, so 7FAD, 7NAD+, 7H2O and 7CoA used up
…7FADH2 and 7NADH produced (as well as 8 acetyl coA)

21
Q

What is the initial reaction in the beta oxidation of fatty acids?

A

fatty acid + ATP + coA

  • -> acyl coA + AMP + PPi
  • firstly, fatty acids are converted to an acyl CoA species
  • this reaction is coupled to the hydrolysis of ATP, but instead of going to ADP and Pi, it goes all the way to monophosphate group and PPi
22
Q

What is the initial reaction in the beta oxidation of fatty acids?

A

fatty acid + ATP + coA

  • -> acyl coA + AMP + PPi using acyl coA synthetase
  • firstly, fatty acids are converted to an acyl CoA species
  • this reaction is coupled to the hydrolysis of ATP, but instead of going to ADP and Pi, it goes all the way to monophosphate group and PPi
23
Q

What 4 reactions occur in the beta oxidation cycle following the production of an acyl coA?

A
  1. acyl coA oxidised and FAD reduced to FADH2
  2. hydrated, breaking double bond
  3. another oxidation reaction, NAD+–> NADH
  4. thiolysis- molecule split up and coA displaces acetyl group from acyl coA–> results in acetyl coA (which enters TCA cycle) and an acyl coA species 2C shorter than original
24
Q

What happens to acetyl coA if fat breakdown predominates?

A

e.g. during fasting

acetyl coA forms acetoacetate by condensation–> breaks down into acetone and D-3-hydroxybutyrate (KETONE BODIES)

25
Q

What are some differences between beta oxidation and fatty acid biosynthesis?

A
  • fatty acid biosynthesis involves only 2 enzymes: acetyl coA carboxylase and fatty acid synthase
  • condensing acetyl coA w/ malonyl coA
  • following each round of elongation, the fatty acid undergoes reduction and dehydration and reduction
  • acyl carrier proteins vs coA
  • NADPH vs FAD/NAD+
  • synthesis in cytoplasm
26
Q

What is MCADD?

A
  • medium chain acyl-coenzyme A dehydrogenase
  • autosomal recessive
  • adhere to a high carbohydrate diet, or use iv glucose so that body not dependent on fatty acids for energy

PoM Block 1 (8 decks)

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