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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
where are chylomicrons produced?
intestinal epithelia from dietary fat
26
VLDL: where produced, function
produced in liver mainly from dietary CHO - carries TGs in blood
27
IDL
VLDL remnant produced in blood
28
what happens to IDL after TG digestion?
endocytosed by liver or converted to LDL
29
LDL
remnant of IDL after TG digestion, VLDL end product: contains lots of cholesterol and cholesterol esters
30
what is the fate LDL in blood?
endocytosed by liver and peripheral tissues
31
where are LDLs produced?
in blood
32
where are HDLs produced?
liver and intestine
33
HDL fxn
exchanges proteins and lipids for other lipoproteins - returns cholesterol from peripheral tissues to liver
34
which human plasma lipoprotein is most dense and which is least dense?
most dense: HDL | least dense: chylomicron
35
% weight of protein and TG in chylomicrons
protein: 2 TG: 88
36
% weight of protein and TG in VLDL
protein: 10 TG: 54
37
% weight of protein and TG in LDL
protein: 23 TG: 11
38
% weight of protein and TG in HDL
protein: 55 TG: 4
39
location of ApoA-1?
HDL
40
function of ApoA-1?
activates LCAT + structural role
41
location of ApoB-100?
VLDL, LDL
42
function of ApoB-100?
binds LDL receptor + structural role
43
location of ApoB-48?
chylomicron
44
function of ApoB-48?
structural role
45
location of ApoCII?
chylomicrons, VLDL, HDL
46
function of ApoCII?
activates lipoprotein lipase
47
location of ApoE?
chylomicron, VLDL, HDL
48
function of ApoE?
binds to LDL receptor - triggers clearance of VLDL and chylomicron remnants
49
what two apoproteins are encoded together on a single gene?
B-48: intestine (chylomicrons) | B-100: liver (VLDLs)
50
what is the mRNA difference b/w ApoB-48 and ApoB-100?
stop codon difference - C is changed to U in intestine mRNA (B-48)
51
chylomicron fate
once in blood, lipoprotein lipase (LPL) digests TG -> liver picks up remnants w/ apoE receptor
52
lipoprotein lipase
extracellular enzyme anchored to capillary walls of most tissues
53
what is LPL anchored by?
heparin sulfate
54
what is LPL activated by?
apoCII
55
adipose isoenzyme of LPL vs. muscle isoenzyme of LPL
adipose: higher Km, more active after meal when TGs high muscle: lower Km, can obtain FAs even when low conc
56
what stimulates synthesis and secretion of the adipose isoenzyme of LPL?
insulin
57
de novo synthesis of FAs
primarily in the liver from 2C compounds - excess carb consumption, stored as TG in adipose tissue
58
is de novo synthesis of FAs the exact reverse of B-oxidation? why or why not?
no - completely different set of enzymes, occurs in cytosol, not mitochondria, and uses NADPH
59
what do both stages of de novo FA synthesis use?
acetyl-coA and multifunctional proteins in enzyme complexes
60
what multifunctional protein does stage 1 of de novo FA synthesis use?
acetyl-coA carboxylase
61
what multifunctional protein does stage 2 of de novo FA synthesis use?
FA synthetase
62
what are the ingredients for FA synthesis?
cytosolic acetyl-coA exported from mito as citrate and NADPH from PPP and malate -> pyruvate rxn
63
what does insulin/glucagon ratio induce synthesis of?
pyruvate DH, malic enzyme, citrate lyase
64
what does acetyl-coA carboxylase produce?
malonyl coA
65
what does malonyl coA inhibit and why?
CPT1 - when making malonyl coA, don't want it transported into mitochondria for breakdown
66
what cofactor does acetyl-coA carboxylase require?
biotin
67
acetyl-coA carboxylase reaction
acetyl-coA + bicarb + ATP -> malonyl-coA + water + ADP + Pi
68
which is more active: polymer or monomer of acetyl-coA carboxylase?
polymer
69
how is acetyl-coA carboxylase regulated?
- citrate: polymerization and activation - palmitoyl-coA: inhibition - high calorie diet: induces transcription - phosphorylation: inactivation - insulin: activates (dephosphorylates)
70
function of FA synthase complex
sequentially adds 2C units from malonyl coA to the growing FA chain
71
FA synthase complex composition
1 protein: 7 different enzyme activities + acyl-carrier protein; dimer of identical polypeptides arranged head to tail
72
how many cycles of FA synthase occur before the final step of FA synthesis?
6
73
what is the final step of FA synthesis?
thioesterification to palmitate
74
what reactions occur in each cycle of FA synthase?
CRDRS: - condensation - reduction - dehydration - reduction - scoot over (transacetylation)
75
what is located at each end of each FA synthase polypeptide?
SH - one derived from the vitamin pantothenic acid and one from a terminal Cys
76
what is the significance of the SH groups on FA synthase polypeptide?
can form thioesters with the acyl groups
77
what enzymes perform each reaction in one FA synthase cycle?
``` condensation = synthase reduction = reductase dehydration = dehydratase reduction = reductase scoot over = transacylase ```
78
which two reactions in the FA synthase cycle use NADPH?
the reductases
79
FA synthesis balanced equation
8 acetyl-coA + 7 ATP + 14 NADPH + 14 H+ --> palmitate + 8 coASH + 7 ADP + 7 Pi + 14 NADP+
80
difference b/w FA synthesis and FA oxidation
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
what stimulates FA synthase gene expression?
high insulin/glucagon ratio
82
what transcription factors are associated w/ FA synthase gene expression?
USFs (upstream stimulatory factors) and SREBPs (sterol response element binding proteins)
83
FA modifications
- 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
where does elongation of FAs occur?
in ER
85
what enzyms is responsible for elongation of FAs?
FA elongase
86
what is a common product of FA elongation from palmitate?
steric acid (18C)
87
what provides 2C units that are added onto palmitate?
malonyl-coA
88
what provides the reducing equivalents for FA elongation?
NADPH
89
what organ makes very long chain FAs (22-24 C) ?
brain
90
what is Stargardt-like macular degeneration?
juvenile eye disease caused by mutations in elongation of very long FAs - ELOVL4 gene
91
where does desaturation of FAs occur?
in ER
92
what is required for desaturation of FAs?
molecular oxygen
93
three enzyme steps for desaturation of FAs?
1. NADH-cyt b5 reductase (flavoprotein w/ FAD) 2. cytochrome b5 (uses Fe) 3. desaturase (uses Fe coordinated to His)
94
what is the limit of human desaturases?
cannot add db's past C-9
95
what are the most common human desaturated FAs?
palmitoleic acid - 16:1^9 | oleic acid - 18:1^9
96
synthesis of TGs
glycerol or glucose -> glycerol-3-P -> phosphatidate -> diacylglycerol -> triacylglycerol -> transported in blood by VLDLs or stored in adipose tissue
97
where is glycerol kinase not found?
adipose tissue -> so glycerol in adipose is returned to liver
98
what is the primary site of lipid synthesis?
liver, but also can be done by adipose tissue
99
what stimulates synthesis and secretion of LPL?
insulin
100
how does phosphorylation affect hormone sensitive lipase?
activates it
101
what phosphorylates HPL?
protein kinase A
102
what regulates protein kinase A in the phosphorylation of HPL?
(+) increased cAMP | (+) low insulin/high glucagon
103
phospholipid synthesis
glycerol-3-P -> -> phosphatidate -> CDP-diacylglycerol -> phosphatidyl inositol (inositol - N head group)
104
second mechanism of phospholipid synthesis
head group (Ser) reacts w/ CTP to form CDP-serine then reacts with diacylglycerol
105
what is the key intermediate in phospholipid synthesis?
CDP-intermediate
106
respiratory distress syndrome
failure to produce enough phosphotidylcholine in lung surfactant
107
phospholipid degradation
cleaved by various phospholipases
108
what is special about the C2 fatty acid of phospholipids and what is done with it?
tends to be unsaturated (e.g. arachidonate) - cleaved in membrane by phospholipase A2 for prostaglandin synthesis
109
what are sphingolipids important for?
myelin sheath on nerve cells and antigenic determinants for the ABO blood groups
110
sphingolipid synthesis
serine + palmitoyl coA -> -> sphingosine -> (acylation of amino group) -> ceramide -> (add phosphatidyl choline, release diacylglycerol) -> sphingomyelin
111
what do gangliosides and cerebrosides add onto ceramide instead of choline?
sugar head groups
112
what generic pathway causes more problems for spingolipids and ceramides: synthesis or breakdown?
breakdown

Biochem - Exam 2 (5 decks)

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