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Biochemistry > Fatty Acid Metabolism > Flashcards

Fatty Acid Metabolism Flashcards

1
Q

name 3 sources of lipids and fatty acids

A
  • diet
  • adipose storage
  • synthesis and tissue
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2
Q

what is the difference between lipids and fatty acids?

A
  • lipids are bigger, essentially multiple fatty acids
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3
Q

what are the 4 fates of lipids and fatty acids?

A
  • energy substrates
  • precursors
  • structural elements
  • signaling molecules
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4
Q

are lipids and fatty acids more or less energy dense than glucose?

A

more

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5
Q

describe the 7 steps of fatty acid digestion (exogenous pathway)

A
  1. bile salts emulsify dietary fats in the small intestine, forming mixed micelles
  2. intestinal lipases degrade triacyl-glycerols
  3. FAs are taken up by the intestinal mucosa and converted to triacylglycerols
  4. triacylglycerols are incorporated, with cholesterol and apolipoproteins, into chylomicrons
  5. chylomicrons move through lymphatic system and bloodstream to tissues
  6. lipoprotein lipase, activated by apoC-II in the capillary, converts triacylglycerols to FAs and glycerol
  7. FAs enter myocyte or adipocyte and are oxidized as fuel or reesterified for storage (oxidation produces ATP and CO2); chylomicron remnants go back to the liver
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6
Q

what are chylomicrons?

A
  • dietary tryglyceride transport
  • synthesized in enterocyte ER
  • transport FAs for fuel or storage
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7
Q

what are apolipoproteins?

A
  • lipid binding proteins
  • combine with lipids to form lipoproteins
  • diverse functions
  • activate lipases
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8
Q

what 2 ways are FAs transported?

A
  1. free fatty acids: carried by serum albumin through vasculature
  2. lipoproteins: proteins that have phospholipid monolayer and cholesterol component; ex. chylomicron
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9
Q

what are lipoproteins?

A
  • phospholipid, cholesterol, and protein membrane-bound vesicles containing triglycerides
  • contain triacylglycerols, free cholesterol, chilesterol esters, and a phopsholipid monolayer
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10
Q

what are the 4 classes of lipoproteins?

A
  1. chylomicrons - largest, packed with triglycerides
  2. very low density lipoprotein (VLDL) - packed with triglycerides
  3. low density lipoprotein (LDL) - decreased triglycerides
  4. high density lipoprotein (HDL) - decreased triglycerides
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11
Q

draw the steps of triglyeride and cholesterol transport by lipoproteins via the endogenous pathway

A
  • C = cholesterol
  • CE = cholesterol ester
  • FFA = free fatty acid
  • IDL = intermediate-density lipoprotein
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12
Q

what does VLDL do?

A

delivers fatty acids to target tissues

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13
Q

what do LDL and HDL do?

A

transport cholesterol

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14
Q

describe the 6 steps of target, internalization, and degradation of lipoproteins

A
  1. LDL receptor synthesized in RER moves to plasma membrane via golgi apparatus
  2. LDL receptor binds apoB-100 on LDL, initiating endycytosis
  3. LDL is internalized in endosome
  4. LDL receptor is segregated into vesicles, recycled to surface
  5. endosome with LDL fuses with lysosome
  6. lytic enzymes in lysosome degrade apoB-100 and choesterol esters, releasing amino acids, fatty acids, and cholesterol

FA are then released into blood stream and can interact with serum albumin, and are then transported to target tissues

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15
Q

what is the triacylglycerol cycle?

A
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16
Q

what percentage of lipids released from adipose are utilized for fuel?

A
  • 25%
  • the rest are recycled
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17
Q

draw out the steps of adipose triacylglycerol mobilization from adipose tissue

A
  • PKA = protein kinase A
  • CGI = comparative gene indicator
  • ATGL = adipose triglyceride lipase
  • MGL = monoglyceride lipase

*important to remember that in step 1, glucagon is coming from the pancreas in response to low blood glucose

*perilipin stabilizes lipid droplet surfaces to trap triglycerides

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18
Q

what do lipases do?

A
  • lipase breaks down triglyceride into glycerol and fatty acid
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19
Q

when lipase breaks down triglycerides, what is the fate of the fatty acid chains?

A
  • forms fatty acyl-CoA
  • accounts for 95% of the energy produced from breaking down triglycerides
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20
Q

when lipases break down triglycerides, what is the fate of the glycerol?

A
  • enters glycolysis
  • accounts for 5% of the total energy produced from breaking down the triglyceride
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21
Q

when triglycerides are broken down, fatty acids produce fatty acyl-CoA. where is the fatty acyl-CoA transported?

A
  • it is transported to the mitochondria for oxidation
  • utilizes acyl-carnitine/carnitine transporter
  • CoA passes off its acyl chain to a carnitine acyltransferase molecule on the outer mitochondrial membrane

it is then passed into the intermembrane space

Then goes through acyl-carnitine/carnitine transporter on inner mitochondrial membrane

***acyl-carnitine/carnitine transporter is an antiport – as the acyl chain/ carnitine complex moves in, a carnitine molecule moves out

Entire acyl-carnitine complex gets moves into the matrix

Carnitine passes acyl chains off to CoA that is already in the matrix

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22
Q

what are the 3 stages of fatty acid oxidation?

A
  1. beta-oxidation: breaking down acyl chain into 2-C sections, creates 8 acetyl-CoA molecules that feed into the CAC, and NADH & FADH2 that feed into oxidative phosphorylation
  2. citric acid cycle also produces NADH and FADH2 that feed into oxidative phosphorylation
  3. oxidative phosphorylation
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23
Q

how many ATP molecules are produced during oxidation of a single fatty acid?

A
  • 108
  • this is a very efficient way to store energy
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24
Q

what are the steps of fatty acid beta oxidation? what are the products of each oxidation step?

A

per oxidation step:

  • 1 acetyl CoA - feeds into CAC
  • 1 NADH + H+
  • 1 FADH2

*don’t need to know each individual steps, but know products and acyl-CoA dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase enzymes and what they form

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25
Q

T or F:

in fatty acid beta oxidation, odd carbon and unsaturated fatty acids undergo additional oxidation steps

A

true

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26
Q

what is the function of the FADH2 produced from acyl-CoA dehydrogenase used in fatty acid beta oxidation? what about the NADH + H+ produced by beta-hydroxyacyl-CoA dehydrogenase?

A

they both feed directly into the electron transport chain

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27
Q

what are the two possible fates of acetyl-CoA formed from fatty acid beta oxidation?

A
  • primarily feeds into CAC to produce oxaloacetate which undergoes gluconeogenesis (basically form energy)
  • can form ketone bodies in cases where gluconeogenesis is saturated
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28
Q

what 3 molecules are ketone bodies?

A
  1. acetoacetate
  2. acetone
  3. D-beta-hydroxybutyrate

remember, these are produced from acetyl-CoA

29
Q

ketone bodies are a fuel source for what tissues? which ketone body is the exception and why?

A
  • heart
  • skeletal muscle
  • kidney
  • brain
  • acetone is the exception because it is toxic (build-up can cause ketoacidosis; can also cause breath to smell sweet)
30
Q

which 2 dietary components form acetyl-CoA?

A
  • dietary CHOs form glucose, which forms acetyl-CoA
  • dietary proteins form amino acids, which form acetyl-CoA
  • insulin will increase the production of acetyl-CoA
31
Q

which of the 3 ketone bodies can be converted back to acetyl-CoA?

A

D-beta-hydroxybutyrate and acetoacetate

32
Q

the presence of what hormone drives excess acetyl-CoA to the formation of fatty acids?

A

insulin

33
Q

how does excess acetyl-CoA form fatty acids?

A
  • acetyl-CoA converted to malonyl-CoA
  • malonyl-CoA + acetyl-CoA forms palmitoyl-CoA
  • fatty acid synthase converts palmitoyl-CoA to palmitic acid (16-C), which can then be used to make fatty acids
34
Q

name the 5 stages of fatty acid synthesis

A
  1. transport of acetyl-CoA to the cytoplasm
  2. carboxylation of acetyl-CoA into malonyl-CoA
  3. fatty acid synthase combines acetyl-CoA and malonyl-CoA to start an acyl chain
  4. fatty acid synthase adds malonyl-CoA to create palmitate (a fatty acid)
  5. fatty acids modified in the ER
35
Q

what occurs in the cytosol of animal and yeast cells?

A
  • NADPH production
  • isoprenoid and sterol synthesis
  • fatty acid synthesis
36
Q

what happens in the ER of animal cells, yeast cells, AND plant cells?

A
  • phospholipid synthesis
  • sterol synthesis
  • fatty acid elongation
  • fatty acid desaturation
37
Q

what is the citrate shuttle? what is the problem it alleviates?

A
  • acetyl-CoA is produced in the mitochondria matrix, but FA synthesis occurs in the cytoplasmic space
  • the citrate shuttle is the solution to this problem
  • components for FA synthesis are shuttled across mitochondrial membranes in the form of citrate via citrate transporter
  • acyl chains are then used for FA synthesis in the cytosol
38
Q

what is the function of acetyl-CoA carboxylase?

A
  • it carboxylates acetyl-CoA to form malonyl-CoA
  • utilizes biotin which is acquired from the diet - vit B7
  • rate limiting step of lipid formation (where it is regulated)
39
Q

what are the 2 types of fatty acid synthase?

A
  • FAS I - vertebrates and fungi; produces 16 C saturated fatty acids
  • FAS II - bacteria and plants; produces fatty acids with chains longer than 16 C
40
Q

what is an acyl carrier protein?

A
  • it is a FAS prosthetic group
  • shuttles malonyl groups to FAS
  • contains pantothenic acid - vit B5; necessary for acyl carrier proteins
41
Q

how many active fatty acid synthase domains are there?

A

7

42
Q

what is the function of fatty acid synthase?

A

it initiates acyl chain formation in lipid synthesis

43
Q

name 2 essential fatty acids

A
  • linoleate and alpha-linolenate
  • formed by FASII and palmitate in plants only (that is why they are essential - we must get them from our diet)
44
Q

what molecule regulates fatty acid synthesis and fatty acid beta oxidation?

A
  • activity of acetyl-CoA carboxylase
45
Q

describe the coordinated regulation of FA synthesis and breakdown

A
  • active ACC converts excess Acetyl CoA (from glycolysis, which occurs in the mitochondria) to malonyl coa; this reaction occurs in cytoplasmic space
  • Inactive ACC leads to FA breakdown
46
Q

the addition of what to fatty acid forms phospholipids and triglycerides?

A
  • phosphatidic acid
  • phosphatidic acid is formed by glucose and glycerol
  • head groups and fatty acids are added to phosphatidic acid
  • occurs in the ER of most cells
47
Q

the removal of a phosphate group from, and addition of fatty acid chain to phosphatidic acid creates what?

A

triglycerol

48
Q

the addition of a head group to phosphatidic acid creates what?

A

phospholipid

49
Q

excess acetate leads to the formation of what?

A
  • cholesterol via acetyl-CoA
50
Q

cholesteral is the basis of what other molecules?

A
  • hydroxysterols
  • bile acids
  • cholesteryl ester
  • steroid hormones
51
Q

describes the steps involved in cholesterol driving atherosclerotic plaque formation

A
52
Q

what 7 hormones is cholesterol the precursor for?

A
  • pregnenolone
  • progesterone
  • cortisol
  • corticosterone
  • testosterone
  • estradiol
  • aldosterone
53
Q

what are some characteristics of lipoprotein content as you move from VLDL to HDL?

A
  • higher density
  • more protein
  • more phospholipids
  • less triglycerides
54
Q

what occurs during the exogenous pathway, endogenous pathway, and reverse cholesterol transport? (very basic)

A
  • exogenous pathway: digestion of fats, chylomicrons release FAs in vasculature, chylomicron remants returned to liver
  • endogenous pathway: VLDL from liver releases FA and is converted to LDL in vasculature, returned to liver as LDL
  • reverse cholesterol transport: HDL lipoproteins from the liver take up excess cholesterol from macrophage foam cells and return them to the liver
55
Q

draw the steps of triglyeride and cholesterol transport by lipoproteins via the exogenous pathway

A

C = cholesterol

CE = cholesterol ester

FFA = free fatty acid

IDL = intermediate-density lipoprotein

56
Q

draw the steps of triglyeride and cholesterol transport by lipoproteins via reverse cholesterol transport

A

C = cholesterol

CE = cholesterol ester

FFA = free fatty acid

IDL = intermediate-density lipoprotein

57
Q

how do fatty acids form fatty acyl-CoA?

A
  • fatty acyl-CoA synthetase and ATP forms a fatty acyl-adenylate and PPi.
  • fatty acyl-CoA synthetase forms fatty acyl-CoA and AMP
58
Q

in beta oxidation, which carbon is oxidized?

A

the beta carbon!

59
Q

what happens in the mitochondria of animal cells?

A
  • fatty acid oxidation
  • acetyl-coa production
  • ketone body synthesis
  • fatty acid elongation
60
Q

what happens in the chloroplasts of plant cells?

A
  • NADPH, ATP production
  • fatty acid synthesis
61
Q

what happens in peroxisomes of plant cells?

A
  • fatty acid oxidation
62
Q

malonyl-CoA is necessary for what?

A

acyl chain initiation and synthesis

63
Q

describe how fatty acid synthase initiates acyl chain formation

A
  • Acetyl coa donates acetyl group to FAS
  • Acyl carrier protein takes malonyl group from malonyl coa
  • Condensation reaction occurs; acetyl group and malonyl group come together
  • Forms beta and alpha carbons for fatty acid; beta end is from acetyl group, alpha end is from malonyl group
  • Beta carbon is reduced via reduction steps which occur by NADPH (produces NADP); NADPH reduces the beta carbon; it is the electron donor (NADPH is a product of the pentose phosphate pathway)
  • Acyl carrier protein keeps adding malonyl groups (2 C per malonyl group) via reduction steps, until 16 C palmitate molecule is formed
64
Q

is palmitate is the only product of fatty acid synthase?

A

yes

65
Q

describe how activated ACC drives the production of fatty acids

A

the conversion of acetyl-CoA to malonyl-CoA serves 2 functions:

  1. malonyl-CoA forms fatty acids
  2. malonyl-CoA inhibits the breakdown of fatty acids in the mitochondrial matrix by inhibiting carnitine acyl-transferase
66
Q

describe how inactivated ACC drives the breakdown of fatty acids

A
  • conversion of acetyl-CoA to malonyl-CoA cannot occur unless ACC is activated
  • no malonyl-CoA = no fatty acid synthesis
  • in the absence of malonyl-CoA, carnitine acyl-transferase can function to drive the reaction of fatty acid breakdown in the mitochondrial matrix
67
Q

how is fatty acid synthesis and breakdown regulated when blood glucose is high?

A

high blood glucose = fatty acid synthesis

  • pancreas releases insulin
  • ​insulin allows phosphatase to dephosphorylate inactivated ACC, causing it to become active
  • activated ACC will convert excess acetyl-CoA to malonyl-CoA
  • ​malonyl-CoA synthesizes fatty acids and inhibits carnitine acyl-transferase
68
Q

how is fatty acid synthesis and breakdown regulated when blood glucose is low?

A

low blood glucose = fatty acid breakdown

  • pancreas releases glucagon
  • glucagon allows protein kinase A to phosphorylate ACC, causing it to become inactive
  • no conversion of acetyl-CoA to malonyl-CoA
  • carnitine acyl-transferase can function, allowing the breakdown of fatty acids in the mitochondrial matrix

Biochemistry (32 decks)

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