Diabetes, HDL and Tangier Disease

Question 1

how are most calories stored in the body?

Answer 1

TGs

Question 2

how many calories/gram in TGs? And glycogen?

Answer 2

9 (TGs) and 1 (glycogen)

Question 3

what are some advantages afforded to humans by the brain to utilize ketones as fuel?

Answer 3

1) TGs as are precursors of ketones are light but calorically dense and easier to move 2) less reliance on skeletal muscle amino acids for gluconeogenesis allows for preservation of muscle mass and 3) maintenance of larger brain size

Question 4

what is autophagy?

Answer 4

cells degrade their own machinery to ensure cell survival during nutrient limitation, but could cause cell/organ death which is normally restrained by insulin

Question 5

describe reverse cholesterol transport

Answer 5

this is a pathway where excess lipids are cleared from the periphery and brought back into the liver for elimination

the liver and intestines create apoA1 proteins and combine with PLs and cholesterol in the periphery to form discoidal nascent HDL

LCAT enzyme converts discoidal nascent HDL into HDL3 and HDL2 by adding more cholesterol esters, which are then delivered the the liver

Question 6

describe the two methods for delivery of HDL cholesterol

Answer 6

1) HDL3 and HDL2 are recognized by the HDL receptor (SR-B1) in the liver and adrenal cortex and are metabolized for the reutilization of cholesterol esters 2) cholesterol ester transfer protein transffers cholesterol esters to VLDL, LDL, or IDL in exchange for TGs or PLs and they are received by LDLRs

Question 7

describe Tangier disease

Answer 7

rare genetic disease where the ABCA transporter does not transfer the cholesterol to apoA1, causing low levels of HDL and cellular accumulation of cholesterol signs include enlarged spleen, liver, ocular abnormalities, orange tonsils

Question 8

describe the structure of ABCA

Answer 8

ATP dependent protein is comprised of a single strand and can be organized into 2 6-membrane spanning helices, each with an ATP binding site, and a hydrophobic regulator site between ABCA draws pools of excess cholesterol intracellularly, but it is unclear how it is monitored

Question 9

describe genetic regulation of ABCA

Answer 9

ABCA gene has a direct repeat response element called DR-4 in the promoter region, which cna bind LXR or RXR or both, these both upregulate the expression of ABCA and are synergistic, LXR responds to oxysterols and RXR repsonds to 9-cis-retinoic acid