Fatty Acid Metabolism I Lec. 35 Flashcards
monoglyceride
diglyceride
triglyceride
one fatty acid attached to glycerol
two fatty acid attached to glycerol
three fatty acid attached to glycerol
cholesterol
hydrophobic molecule that has a free hydroxyl group that gives it polarity
what happens to the cholesterol that we consume through our dietary intake?
the cholesterols will be converted into cholesterol esters (not all of them but a very large part of them)
adipose tissue
- fat tissue that is the major storage site for fats
- the filled with lipids (triglycerides) or lipid droplets
- an endocrine organ
adipocytes
these are the major cell type of adipose tissue (lipid storage)
fasting state
have not eaten for a period of time with elevated levels of glucagon in our body
what is the two hormones that tells us that we are hungry?
ghrelin and leptin
ghrelin hormone
this hormone tells us when we are hungry and need to eat
- very small peptide hormone that is released by our stomach and travels through the bloodstream to our brains to signal the hunger
- ghrelin levels will be high when we have not eaten or after will rise after we have eaten
leptin hormone
- released by adipose tissue (adipose tissue is an endocrine organ) and it acts on the hypothalamus to reduce the hunger drive
- elevated in people who are obese
why are leptin levels high in obese individuals?
the theory of leptin resistance tells us that obese individuals become desensitized to effects of leptin due to chronically elevated leptin levels
where does lipid digestion (fat digestion) primarily take place?
within the small intestine
triglycerides
these are highly hydrophobic
- they pack into large lipid globules
what happens to fat globules in the small intestine?
- within the small intestine fat globules will be mixed with bile salts to break down the globules in smaller ones
- this gives a larger surface area for enzymes to act on (more globules to act on)
what is the enzyme that hydrolyzes triglycerides
pancreatic lipase
- its released by the pancreas into the small intestine and will cleave the triglycerides (cleaves at the 1 and 3 positions) into two fatty acids and a 2-monoglycerol (MAG) within the small intestine
what is the mechanism of the pancreatic lipase?
this enzyme acts by cleaving triglycerides at the 1 and 3 positions which will produce 2 fatty acids and a 2-monoacyglycerol
what would happen if the pancreatic lipase enzyme was inhibited?
our bodies would not be able to absorb triglycerides and ultimately become obese
what happens to fatty acids that are taken up intestinal cells?
they will be synthesized back into triglycerides
what is the structure of chylomicrons?
- chylomicrons have tightly packed cores filled with triglycerides and cholesterol esters (both of which are highly hydrophobic)
- the core is surrounded by a phospholipid monolayer (only one layer of phospholipids)
- charged phospholipid heads face the outside while the tail faces the inside (interior)
- free cholesterol is embedded within the phospholipid monolayer
what is the mechanism of chylomicron synthesis?
these are going to be synthesized within the small intestine within the intestinal cells
what can embedded in the phospholipid monolayer of chylomicrons? (free cholesterol, ester cholesterol, both, or neither)
only free cholesterol can embed into the mono phospholipid layer - the cholesterol ester cannot
- proteins also embed on the layer as well
can triglycerides be released into the blood stream?
no they are too insoluble (too hydrophobic) to be released within the bloodstream – chylomicrons are used to transport high hydrophobic molecules through the blood stream instead
where is lipoprotein lipase (LPL) found? what is their function?
it lines the epithelium of capillaries surrounding adipose and muscle tissue
- they degrade the triglycerides into free fatty acids and the 2-monoacylglycerols that are within the chylomicron structure
- so the free fatty acids will either be taken up by muscle tissue for energy or by adipose tissue to be stored
- need to know that this enzyme does not cleave cholesterol esters
what happens to the chylomicron remnants?
the chylomicron remnants are highly enriched in cholesterol esters since the lipoprotein lipase does not breakdown the cholesterol esters; so these dietary cholesterol will be taken up by the liver - however the triglycerides of the chylomicron will be taken up by either muscle or adipose tissue
would would happen to someone who has defective lipoprotein lipase?
the fatty acids would not be able to be taken up and the chylomicrons within the bloodstream would keep accumulating in the blood
what happens if you have a lipoprotein lipase deficiency?
- an individual would have elevated chylomicrons within the blood stream, leading to elevated triglycerides and elevated cholesterol
what is the structure of lipid droplets (fat molecules)? what do they compose of?
they are structurally similar to chylomicrons and have an inner core of triglycerides and cholesterol esters which are surrounded by a phospholipid monolayer
- the lipid monolayer has acyl chains facing the interior
- free cholesterol embedded in monolayer and proteins on the outside of the lipid droplet
what is the main difference between a chylomicron and a lipid droplet?
the lipid droplets are intracellular - so they are found on the inside of cell
- they are also a storage site for excess fat
- lipid droplets are also dynamic in the sense that they can grow and shrink depending upon the rate of lipid turnover - the fusing of lipid droplets will become very large lipid globules and an obese person will store and grow more and more of these
how is lipolysis stimulated?
- through fasting (release of glucagon)
- fight or flight (epinephrine/adrenaline)
- lipolysis results in the hydrolysis of stored triglycerides into fatty acids within adipose tissue, which are subsequently released for use by other tissues (i.e. muscle tissue)
what enzymes are responsible for the enzymatic conversion of triglycerides into fatty acids?
ATGL - adipocyte triglyceride lipase
HSL - hormone sensitive lipase
MAGL/MGL - monoacylglycerol lipase
*** all of these enzymes will break down and cleave the free fatty acids from glycerol one at a time, and is only done in extreme times of energy
ATGL (adipocyte triglyceride lipase) enzyme does what in relation to enzymatic conversion of triglycerides to fatty acids?
this is a lipase that cleaves lipoprotein lipids and is specific for triglycerides which produces a di-glyceride
HSL (hormone sensitive lipase) enzyme does what in relation to enzymatic conversion of triglycerides to fatty acids?
this will cleave the diglyceride at the ester linkage and form a mono acyl glyceride
MAGL (monoacylglycerol lipase)
this enzyme will cleave the ester bone and generate a free fatty acid
how is lipolysis regulated? what is the mechanism?
- when glucagon or epinephrine activates its receptor it leads to the activation of a protein called protein kinase A or PKA and that PKA is going to phosphorylate two proteins (perilipin-1 and ABHD5) and the protein, ABHD5, will recruit triglyceride lipase to the lipid droplet
- this occurs during the starvation- state
what are the two proteins that will be phosphorylated by protein kinase A that’s involved in lipolysis?
perilipin-1 and ABHD5
- together they form a complex but once the protein kinase A activates them they will dissociate and separate
what is the major role of the protein ABHD5 which is involved in regulation of lipolysis?
the protein will recruit adipocyte triglyceride lipase to the lipid droplets
- we do not want this to occur when we are in the fed state
chanarin-dorfman syndrome
this syndrome is associated with the protein ABHD5 due to a mutation in the protein that results in the protein nonfunctioning
- it is a rare autosomal recessive lipid storage disease
- seen in patients with hepatomegaly (enlarged livers)
