Lipid Transport and Storage

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Lipid Transport and Storage

• Medical Biochemistry
• Lectures 54 and 55

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CLINICAL ASPECTS

• 1. Imbalance in the rate of triacylglycerol
  formation and export causes fatty liver. 
• Accumulation of lipid as triacylglycerol in the
  liver causes cirrhosis and impaired liver
  function.

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Fatty liver falls into two categories

• a. Raised levels of plasma free fatty acids
  resulting from mobilization of fat from adipose
  tissue or from the hydrolysis of lipoprotein
  triacylglycerol by lipoprotein lipase in
  extrahepatic tissues. 
• Increasing amounts of free fatty acids are taken
  up by the liver and esterified. The production
  of VLDL does not keep pace with the influx of
  free fatty acids, allowing triacylglycerol to
  accumulate, causing fatty liver. 
• During starvation, quantity of triacylglycerol in
  the liver is increased, and ability to secret
  VLDL is impaired. This may be due to low levels
  of insulin.

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• Due to a metabolic block in the production of
  plasma lipoproteins, thus allowing
  triacylglycerol to accumulate. 
• Lesion could be due to 
• 1. A block in apolipoprotein synthesis
• 2. A block in the synthesis of lipoprotein from
  lipid and apolipoprotein
• 3. A failure in the secretory mechanism itself.
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• In experimental animals, deficiency of choline,
  treatment with puromycin, ethionine, carbon
  tetrachloride, chloroform, phosphorous, lead, and
  arsenic causes fatty liver.

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Ethanol also causes fatty liver Alcoholism
leads to fat accumulation in the liver,
hyperlipidemia, and ultimately cirrhosis
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• A. Increased NADH/NAD ratio causes
• Shift in the malate oxaloacetate, which may
  reduce activity of the citric acid cycle. 
• Net effect of inhibiting fatty acid oxidation is
  to cause increased esterification of fatty acids
  in triacylglycerol, which may be the cause of
  fatty liver. 
• B. also causes increase in lactate/pyruvate
  ratio that results in hyperlacticacidemia, which
  in turn decreases the capacity of kidney to
  excrete uric acid.
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• C. Increase in acetyl-CoA causes increased
  lipogenesis and cholesterol

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