Fatty Acid Metabolism I Lec. 35 Flashcards

1
Q

monoglyceride
diglyceride
triglyceride

A

one fatty acid attached to glycerol
two fatty acid attached to glycerol
three fatty acid attached to glycerol

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2
Q

cholesterol

A

hydrophobic molecule that has a free hydroxyl group that gives it polarity

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3
Q

what happens to the cholesterol that we consume through our dietary intake?

A

the cholesterols will be converted into cholesterol esters (not all of them but a very large part of them)

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4
Q

adipose tissue

A
  • fat tissue that is the major storage site for fats
  • the filled with lipids (triglycerides) or lipid droplets
  • an endocrine organ
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5
Q

adipocytes

A

these are the major cell type of adipose tissue (lipid storage)

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6
Q

fasting state

A

have not eaten for a period of time with elevated levels of glucagon in our body

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7
Q

what is the two hormones that tells us that we are hungry?

A

ghrelin and leptin

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8
Q

ghrelin hormone

A

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
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9
Q

leptin hormone

A
  • 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
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10
Q

why are leptin levels high in obese individuals?

A

the theory of leptin resistance tells us that obese individuals become desensitized to effects of leptin due to chronically elevated leptin levels

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11
Q

where does lipid digestion (fat digestion) primarily take place?

A

within the small intestine

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12
Q

triglycerides

A

these are highly hydrophobic

- they pack into large lipid globules

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13
Q

what happens to fat globules in the small intestine?

A
  • 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)
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14
Q

what is the enzyme that hydrolyzes triglycerides

A

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

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15
Q

what is the mechanism of the pancreatic lipase?

A

this enzyme acts by cleaving triglycerides at the 1 and 3 positions which will produce 2 fatty acids and a 2-monoacyglycerol

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16
Q

what would happen if the pancreatic lipase enzyme was inhibited?

A

our bodies would not be able to absorb triglycerides and ultimately become obese

17
Q

what happens to fatty acids that are taken up intestinal cells?

A

they will be synthesized back into triglycerides

18
Q

what is the structure of chylomicrons?

A
  • 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
19
Q

what is the mechanism of chylomicron synthesis?

A

these are going to be synthesized within the small intestine within the intestinal cells

20
Q

what can embedded in the phospholipid monolayer of chylomicrons? (free cholesterol, ester cholesterol, both, or neither)

A

only free cholesterol can embed into the mono phospholipid layer - the cholesterol ester cannot
- proteins also embed on the layer as well

21
Q

can triglycerides be released into the blood stream?

A

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

22
Q

where is lipoprotein lipase (LPL) found? what is their function?

A

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
23
Q

what happens to the chylomicron remnants?

A

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

24
Q

would would happen to someone who has defective lipoprotein lipase?

A

the fatty acids would not be able to be taken up and the chylomicrons within the bloodstream would keep accumulating in the blood

25
Q

what happens if you have a lipoprotein lipase deficiency?

A
  • an individual would have elevated chylomicrons within the blood stream, leading to elevated triglycerides and elevated cholesterol
26
Q

what is the structure of lipid droplets (fat molecules)? what do they compose of?

A

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
27
Q

what is the main difference between a chylomicron and a lipid droplet?

A

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
28
Q

how is lipolysis stimulated?

A
  • 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)
29
Q

what enzymes are responsible for the enzymatic conversion of triglycerides into fatty acids?

A

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

30
Q

ATGL (adipocyte triglyceride lipase) enzyme does what in relation to enzymatic conversion of triglycerides to fatty acids?

A

this is a lipase that cleaves lipoprotein lipids and is specific for triglycerides which produces a di-glyceride

31
Q

HSL (hormone sensitive lipase) enzyme does what in relation to enzymatic conversion of triglycerides to fatty acids?

A

this will cleave the diglyceride at the ester linkage and form a mono acyl glyceride

32
Q

MAGL (monoacylglycerol lipase)

A

this enzyme will cleave the ester bone and generate a free fatty acid

33
Q

how is lipolysis regulated? what is the mechanism?

A
  • 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
34
Q

what are the two proteins that will be phosphorylated by protein kinase A that’s involved in lipolysis?

A

perilipin-1 and ABHD5

- together they form a complex but once the protein kinase A activates them they will dissociate and separate

35
Q

what is the major role of the protein ABHD5 which is involved in regulation of lipolysis?

A

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

36
Q

chanarin-dorfman syndrome

A

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)