Lipid and ketone Metabolism Flashcards

1
Q

What are the 3 classes of lipids?

A
  • fatty acid derivatives
  • hydroxy- methyl- glutaric acid derivatives (HMG)
  • vitamins A,D,E,K
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2
Q

Give 4 examples of fatty acid derivative lipids?

A
  • fatty acids
  • triglycerides
  • phospphlipids
  • eicosanoids (local mediators)
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3
Q

give examples of HMG lipids?

A

ketone bodies
cholesterol
cholesterol esters
bile acids and salts

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4
Q

Outline happens to triglycerides as they enter the body?

A
  • digested in small intestine lumen by pancreatic lipases
  • recombined in small intestine epethilia
  • transported in blood by lipoproteins (chylomicrons)
  • stored in adipose tissue
  • transported with albumin when needed to consumer tissues which use fatty acid oxidation to produce enegry
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5
Q

What is the general formulae for a fatty acid

A

CH3 (CH2)n (COOH)

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6
Q

Why are poly unsaturated fatty acids essential?

A

we cannot add C=C bonds past C9

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7
Q

outline the dynamic system of storage of triglyceride in adipose tissue

A
  • triglyceride is constantly being broken down to fatty acid and glycerol
  • the glycerol leaves the cell and is metabolised in liver
  • the fatty acid will be released when [glucose] low or combines with coA to create fatty acyl coA
  • Fatty acyl coA combines with glycerol 1P to create fatty acid
  • Glycerol 1P comes from the breakdown of glucose (also creates pyruvate)
  • therefor constant supply of glucose needed for triglyceride storage
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8
Q

When [glucose] is low, the fatty acids cannot be recombined with glycerol to create triglycerides and they are released into blood on albumin. When they they reach consumer tissue, where and how are they activated ready for metabolism?

A

theyre activated in the cytoplasm by linking to coA with energy from ATP
this creates fatty acyl coA, AMP and 2 Pi

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9
Q

How are fatty acyl coA molecules transported into the mitochondrions matrix for catabolism?

A

carnitine shuttle:

  • fatty acyl CoA reacts with carnitine with the CAT1 enzyme to create fatty acyl cartnitine and CoA
  • the carnitine shuttle transporter moves fatty acyl caritine into the matrix
  • fatty acyl carnitine reacts with CoA on the inside of the matrix (with CAT2 enzyme)
  • This creates the fatty acyl coA and carnitine again (carnitine moves back into inner membrane space)
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10
Q

What regulates the rate of fatty acyl coA entering the mitochondrion?

A

the carnitine shuttle is inhibited by malonyl coA from the krebs cycle when energy levels are high

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11
Q

describe the catabolism (B oxidation) of fatty acids

A
  • 2C removed each time, so many cycles needed
  • FADH and NADH created in each cycle
  • H20 and CoA used in each cycle
  • Each cycle produces 1 acetyl co A which enters into the krebs cycle
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12
Q

What happens to the glycerol from the triglyceride?

A
  • Taken to liver
  • Glycerol kinase and ATP convert it to glycerol phosphate
  • This is either used for triglyceride synthesis
  • or oxidised by NAD+ to DHAP which enters glycolysis
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13
Q

Other then entering krebs cycle, what can acetyl co A do?

A
  • enter fatty acid synthesis (by combining with oxaloacetate to citrate which can leave cell and be cleaved agin) to create triglycerides of phospohlipids
  • be converted to HMG to create ketone bodies or cholesterol (for steriod hormones)
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14
Q

What vitamin does acetyl coA contain?

A

B5

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15
Q

What are the 3 types of ketone bodies? How are they all interlinked?

A
  • Acetoacetate
  • (breaks down by sponatneous loss of co2 to form) Acetone)
  • Beta hydroxybutyrate (forms from acetoacetate reduction with NADH)
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16
Q

What are normal, starvation and untreated diabetic levels of ketones in blood plasma?

A

normal- <1mM
starvation- 2-10mM
untreated diabetic- 10+ mM

17
Q

When are ketones produced and why?

A

When insulin: glucagon ratio low (low insulin in diabetes or starving)
released as an alternative source of energy for the liver and muscles to save any glucose for the brain

18
Q

What enzyme converts acteyl coA to HMG CoA?

A

synthase

19
Q

What enzyme converts HMG coA to acetoacetate (ketone bodies) and what enzyme converts HMG coA to mevalonate (and then cholesterol)?

A

HMGcoA–> acetoacetate by lyase

HMG coA–> mevalonate by HMG coA reductase

20
Q

What do statins do and how do they work?

A

they reduce cholesterol levels by inhibiting HMG coA reductase

21
Q

How are ketone bodies catabolised in muscle?

A
  • any b hydroxybutyrate is converted to acetoacetate by NAD+
  • CoA from succinyl CoA added to make acetoacetate CoA
  • This is converted to acteyl coA which is used in krebs cycle
22
Q

How is ketone body production in liver controlled by level of fatty acid catabolism?

A
  • fatty acid catabolism more when starving so we want positive feedback
  • when more fatty acid oxidised to acetyl coA, more NADH produced
  • This inhibits isocitrate and a- ketogluterate dehydrogenases
  • So more acetyl coA builds up
  • so more acetyl coA for ketone body production
23
Q

How is the proportion of HMG coA being converted to ketones increased and cholesterol decreased when starving?

A

low insulin: glucagon ratio inhibits HMGco A reductase and activates lyase so more ketones produced

24
Q

Are ketones watersoluable?

A

yes