Biochemistry Q

[residency2014]

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Could you let me know how each of these dz (diabetes, alcoholism, and Glucose 6-Phosphatase deficiency) leads to hyperTGL and an increase in serum VLDL and chylomicrons? Thanks.

 

[Phloston]

Could you let me know how each of these dz (diabetes, alcoholism, and Glucose 6-Phosphatase deficiency) leads to hyperTGL and an increase in serum VLDL and chylomicrons? Thanks.

Diabetes: decreased insulin / decreased effects of insulin --> decreased lipoprotein lipase activity (decreased chylomicron TGA uptake at peripheral tissues) + increased hormone-sensitive lipase activity (increased release of TGAs from adipose tissue). Remember that the lipoprotein lipase / hormone-sensitive lipase ratio is increased when insulin's effects increase.

Alcohol: increased NADH/NAD+ ratio --> increased conversion of glyceraldehyde stores to glycerol. Then, since gluconeogenesis is impaired (since OAA is shunted to malate via NADH --> NAD+), increased FAs are released into the bloodstream. Glycerol + 3FAs --> TGAs.

Von Gierke's: decreased glucose production from G6P means increased gluconeogenesis. Increased FAs released into the bloodstream.

Alcohol's main effect on cholesterol is increasing HDL.

 

[residency2014]

Thanks for your explanation. It's very helpful. But how is serum VLDL increased in these diseases? This is especially challenging for me to figure out. My understanding is that alcohol increases TGL synthesis in the liver (through the pathways you described) + acetaldehyde disrupts tubulin, leading to decrease in VLDL release --> fatty liver.

 

[Phloston]

Thanks for your explanation. It's very helpful. But how is serum VLDL increased in these diseases? This is especially challenging for me to figure out. My understanding is that alcohol increases TGL synthesis in the liver (through the pathways you described) + acetaldehyde disrupts tubulin, leading to decrease in VLDL release --> fatty liver.

I don't think EtOH leads to increased serum VLDLs. It leads to increased serum HDLs.