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Biochem - Exam 2 > Lipid Uptake Part 1 > Flashcards

Lipid Uptake Part 1 Flashcards

1
Q

How does the body deal with the biochemical problem of lipids having low solubility?

A
  • solubilize with detergents (bile salts)

- associate with proteins for transport (chylomicrons, VLDL, LDL, HDL)

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2
Q

what are the 3 important lipases for lipids?

A
  • hormone sensitive lipase
  • pancreatic lipase
  • lipoprotein lipase
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3
Q

function of hormone sensitive lipase?

A

mobilizes TAGs from adipose tissue

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4
Q

function of pancreatic lipase?

A

digestion of TAGs - converts triacylglycerol -> fatty acids and monoacylglycerol

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5
Q

How does the weight loss drug orlistat/xenical/alli work?

A

reversibly inhibits activity of pancreatic lipase -> prevents absorption of triglycerides

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6
Q

side effects of orlistat/xenical/alli?

A

reduce absorption of fat-soluble vitamins (A,D,E,K), beta-carotene, fatty acids, 2-monoacylglycerol

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7
Q

cholic acid

A

a bile salt w/ ring structure of cholesterol but has more hydroxyls, a polar side chain, and lacks C5-6 db

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8
Q

where are bile salts made?

A

made in liver -> then transferred to gall bladder and released to intestine

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9
Q

how much of bile salts are recycled to liver?

A

95%

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10
Q

what is cholestryamine/cholybar/questran?

A

bile acid sequestrant - binds negatively charged bile and prevents reabsorption

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11
Q

what is cholestryamine/cholybar/questran used to treat?

A

hypercholesterolemia and the itching caused by liver disease and failure to process bile

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12
Q

chemical description of cholestyramine

A

positively charged resin, not soluble in water

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13
Q

what does the use of cholestryamine stimulate in the body?

A

it removes bile acids, which stimulates liver bile acid synthesis from cholesterol -> stimulates LDL receptor in liver, causing reduced serum cholesterol

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14
Q

what does the action of cholestryamine depend on?

A

dose administered

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15
Q

gall bladder problems present how to patients?

A

trouble digesting high fat meal, upper right quadrant abdomen pain

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16
Q

what does the pancreas secrete to aid in absorption of fat?

A

bicarbonate, lipase, colipase

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17
Q

what induces secretion of pancreatic enzymes?

A

gut hormone cholecystokinin

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18
Q

absorption of fats pathway

A

ingest fat -> bile salts bind TGs -> lipase/colipase break TGs down to FA + 2-MG -> bile salts take 2-MG and FA into enterocytes -> remade into TG -> packaged into chylomicrons -> travel through lymph back to blood/ bile salts recycled to liver

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19
Q

absorption of medium and short chain FAs

A

do not need micelles! enter portal blood rather than lymph - travel in blood bound to serum album

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20
Q

absorption of long and very long chain FAs

A

packed into mixed micelles prior to absorption by microvilli on surface of intestinal epithelial cells - reassembled into TGs -> chylomicrons through lymph to blood

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21
Q

what do long and very long chain FA chylomicrons pick up in the blood?

A

apoCII and apoE

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22
Q

how are TAGs digested?

A

lipoprotein lipase (LPL) on capillaries

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23
Q

synthesis of chylomicrons

A

TGs from sER and ApoB-48 from rER combined in golgi, which secretes nascent chylomicrons that are exocytosed to lymph and travel through lymph to blood

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24
Q

what do chylomicrons contain?

A

TAGs, apoproteins, other lipids (cholesterol esters)

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25
Q

where are chylomicrons produced?

A

intestinal epithelia from dietary fat

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26
Q

VLDL: where produced, function

A

produced in liver mainly from dietary CHO - carries TGs in blood

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27
Q

IDL

A

VLDL remnant produced in blood

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28
Q

what happens to IDL after TG digestion?

A

endocytosed by liver or converted to LDL

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29
Q

LDL

A

remnant of IDL after TG digestion, VLDL end product: contains lots of cholesterol and cholesterol esters

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30
Q

what is the fate LDL in blood?

A

endocytosed by liver and peripheral tissues

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31
Q

where are LDLs produced?

A

in blood

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32
Q

where are HDLs produced?

A

liver and intestine

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33
Q

HDL fxn

A

exchanges proteins and lipids for other lipoproteins - returns cholesterol from peripheral tissues to liver

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34
Q

which human plasma lipoprotein is most dense and which is least dense?

A

most dense: HDL

least dense: chylomicron

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35
Q

% weight of protein and TG in chylomicrons

A

protein: 2
TG: 88

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36
Q

% weight of protein and TG in VLDL

A

protein: 10
TG: 54

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37
Q

% weight of protein and TG in LDL

A

protein: 23
TG: 11

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38
Q

% weight of protein and TG in HDL

A

protein: 55
TG: 4

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39
Q

location of ApoA-1?

A

HDL

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40
Q

function of ApoA-1?

A

activates LCAT + structural role

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41
Q

location of ApoB-100?

A

VLDL, LDL

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42
Q

function of ApoB-100?

A

binds LDL receptor + structural role

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43
Q

location of ApoB-48?

A

chylomicron

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44
Q

function of ApoB-48?

A

structural role

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45
Q

location of ApoCII?

A

chylomicrons, VLDL, HDL

46
Q

function of ApoCII?

A

activates lipoprotein lipase

47
Q

location of ApoE?

A

chylomicron, VLDL, HDL

48
Q

function of ApoE?

A

binds to LDL receptor - triggers clearance of VLDL and chylomicron remnants

49
Q

what two apoproteins are encoded together on a single gene?

A

B-48: intestine (chylomicrons)

B-100: liver (VLDLs)

50
Q

what is the mRNA difference b/w ApoB-48 and ApoB-100?

A

stop codon difference - C is changed to U in intestine mRNA (B-48)

51
Q

chylomicron fate

A

once in blood, lipoprotein lipase (LPL) digests TG -> liver picks up remnants w/ apoE receptor

52
Q

lipoprotein lipase

A

extracellular enzyme anchored to capillary walls of most tissues

53
Q

what is LPL anchored by?

A

heparin sulfate

54
Q

what is LPL activated by?

A

apoCII

55
Q

adipose isoenzyme of LPL vs. muscle isoenzyme of LPL

A

adipose: higher Km, more active after meal when TGs high
muscle: lower Km, can obtain FAs even when low conc

56
Q

what stimulates synthesis and secretion of the adipose isoenzyme of LPL?

A

insulin

57
Q

de novo synthesis of FAs

A

primarily in the liver from 2C compounds - excess carb consumption, stored as TG in adipose tissue

58
Q

is de novo synthesis of FAs the exact reverse of B-oxidation? why or why not?

A

no - completely different set of enzymes, occurs in cytosol, not mitochondria, and uses NADPH

59
Q

what do both stages of de novo FA synthesis use?

A

acetyl-coA and multifunctional proteins in enzyme complexes

60
Q

what multifunctional protein does stage 1 of de novo FA synthesis use?

A

acetyl-coA carboxylase

61
Q

what multifunctional protein does stage 2 of de novo FA synthesis use?

A

FA synthetase

62
Q

what are the ingredients for FA synthesis?

A

cytosolic acetyl-coA exported from mito as citrate and NADPH from PPP and malate -> pyruvate rxn

63
Q

what does insulin/glucagon ratio induce synthesis of?

A

pyruvate DH, malic enzyme, citrate lyase

64
Q

what does acetyl-coA carboxylase produce?

A

malonyl coA

65
Q

what does malonyl coA inhibit and why?

A

CPT1 - when making malonyl coA, don’t want it transported into mitochondria for breakdown

66
Q

what cofactor does acetyl-coA carboxylase require?

A

biotin

67
Q

acetyl-coA carboxylase reaction

A

acetyl-coA + bicarb + ATP -> malonyl-coA + water + ADP + Pi

68
Q

which is more active: polymer or monomer of acetyl-coA carboxylase?

A

polymer

69
Q

how is acetyl-coA carboxylase regulated?

A
  • citrate: polymerization and activation
  • palmitoyl-coA: inhibition
  • high calorie diet: induces transcription
  • phosphorylation: inactivation
  • insulin: activates (dephosphorylates)
70
Q

function of FA synthase complex

A

sequentially adds 2C units from malonyl coA to the growing FA chain

71
Q

FA synthase complex composition

A

1 protein: 7 different enzyme activities + acyl-carrier protein; dimer of identical polypeptides arranged head to tail

72
Q

how many cycles of FA synthase occur before the final step of FA synthesis?

A

6

73
Q

what is the final step of FA synthesis?

A

thioesterification to palmitate

74
Q

what reactions occur in each cycle of FA synthase?

A

CRDRS:

  • condensation
  • reduction
  • dehydration
  • reduction
  • scoot over (transacetylation)
75
Q

what is located at each end of each FA synthase polypeptide?

A

SH - one derived from the vitamin pantothenic acid and one from a terminal Cys

76
Q

what is the significance of the SH groups on FA synthase polypeptide?

A

can form thioesters with the acyl groups

77
Q

what enzymes perform each reaction in one FA synthase cycle?

A 
condensation = synthase
reduction = reductase
dehydration = dehydratase
reduction = reductase
scoot over = transacylase
78
Q

which two reactions in the FA synthase cycle use NADPH?

A

the reductases

79
Q

FA synthesis balanced equation

A

8 acetyl-coA + 7 ATP + 14 NADPH + 14 H+ –> palmitate + 8 coASH + 7 ADP + 7 Pi + 14 NADP+

80
Q

difference b/w FA synthesis and FA oxidation

A

synthesis: requires ACP as acyl group carrier, NADPH as e- donor, and malonyl-coA as 2C donor
oxidation: uses coA as acyl carrier, FAD and NAD+ as e- acceptors, and acetyl-coA as 2C product

81
Q

what stimulates FA synthase gene expression?

A

high insulin/glucagon ratio

82
Q

what transcription factors are associated w/ FA synthase gene expression?

A

USFs (upstream stimulatory factors) and SREBPs (sterol response element binding proteins)

83
Q

FA modifications

A
  • elongation of long-chain FAs
  • desaturation - addition of db’s
  • formation of TAGs - storage form
  • formation of phospholipids and sphingolipids
  • formation of prostaglandins from linoleic acid
84
Q

where does elongation of FAs occur?

A

in ER

85
Q

what enzyms is responsible for elongation of FAs?

A

FA elongase

86
Q

what is a common product of FA elongation from palmitate?

A

steric acid (18C)

87
Q

what provides 2C units that are added onto palmitate?

A

malonyl-coA

88
Q

what provides the reducing equivalents for FA elongation?

A

NADPH

89
Q

what organ makes very long chain FAs (22-24 C) ?

A

brain

90
Q

what is Stargardt-like macular degeneration?

A

juvenile eye disease caused by mutations in elongation of very long FAs - ELOVL4 gene

91
Q

where does desaturation of FAs occur?

A

in ER

92
Q

what is required for desaturation of FAs?

A

molecular oxygen

93
Q

three enzyme steps for desaturation of FAs?

A
  1. NADH-cyt b5 reductase (flavoprotein w/ FAD)
  2. cytochrome b5 (uses Fe)
  3. desaturase (uses Fe coordinated to His)
94
Q

what is the limit of human desaturases?

A

cannot add db’s past C-9

95
Q

what are the most common human desaturated FAs?

A

palmitoleic acid - 16:1^9

oleic acid - 18:1^9

96
Q

synthesis of TGs

A

glycerol or glucose -> glycerol-3-P -> phosphatidate -> diacylglycerol -> triacylglycerol -> transported in blood by VLDLs or stored in adipose tissue

97
Q

where is glycerol kinase not found?

A

adipose tissue -> so glycerol in adipose is returned to liver

98
Q

what is the primary site of lipid synthesis?

A

liver, but also can be done by adipose tissue

99
Q

what stimulates synthesis and secretion of LPL?

A

insulin

100
Q

how does phosphorylation affect hormone sensitive lipase?

A

activates it

101
Q

what phosphorylates HPL?

A

protein kinase A

102
Q

what regulates protein kinase A in the phosphorylation of HPL?

A

(+) increased cAMP

(+) low insulin/high glucagon

103
Q

phospholipid synthesis

A

glycerol-3-P -> -> phosphatidate -> CDP-diacylglycerol -> phosphatidyl inositol (inositol - N head group)

104
Q

second mechanism of phospholipid synthesis

A

head group (Ser) reacts w/ CTP to form CDP-serine then reacts with diacylglycerol

105
Q

what is the key intermediate in phospholipid synthesis?

A

CDP-intermediate

106
Q

respiratory distress syndrome

A

failure to produce enough phosphotidylcholine in lung surfactant

107
Q

phospholipid degradation

A

cleaved by various phospholipases

108
Q

what is special about the C2 fatty acid of phospholipids and what is done with it?

A

tends to be unsaturated (e.g. arachidonate) - cleaved in membrane by phospholipase A2 for prostaglandin synthesis

109
Q

what are sphingolipids important for?

A

myelin sheath on nerve cells and antigenic determinants for the ABO blood groups

110
Q

sphingolipid synthesis

A

serine + palmitoyl coA -> -> sphingosine -> (acylation of amino group) -> ceramide -> (add phosphatidyl choline, release diacylglycerol) -> sphingomyelin

111
Q

what do gangliosides and cerebrosides add onto ceramide instead of choline?

A

sugar head groups

112
Q

what generic pathway causes more problems for spingolipids and ceramides: synthesis or breakdown?

A

breakdown

Biochem - Exam 2 (5 decks)

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