FAs, Lipids, and Cholesterol

Question 1

End Point of FA Synthesis

Answer 1

Palmitic Acid

Question 2

Getting Acetyl CoA into Cytosol for FA Synthesis (3 Steps)

Answer 2

ATP binds isocitrate dehydrogenase and inhibits it, causing buildup of citrate
Citrate moved out of mt matrix into cytosol
ATP-citrate lyase acts as opposite of citrate synthase and cleaves it into OAA and Acetyl CoA

Question 3

Acetyl CoA Carboxylase (2)

Answer 3

Gateway to FA synthesis

Converts Acetyl CoA to Malonyl CoA via carboxylation

Question 4

Acetyl CoA Carboxylase Regulation

Answer 4

AMP-dependent kinase (AMPK) phosphodeactivates it into inactive dimer under starving/epinephrine conditions, whereas protein phosphatase dephosphoactivates it into active polymer from insulin

Question 5

Process of FA Synth (7)

Answer 5

Acetyl CoA attaches to cysteine residue of carrier prot
Malonyl CoA attaches to modified pantothenate on that prot
Malonyl decarbox’d, new carbanion attacks acetyl group
Reduction of last carbonyl group via NADPH
Dehydration of new OH/H
Reduction of new double bond via NADPH
Transfers to cysteine residue, new malonyl CoA added to pantothenate, cycled continues to palmitate (16C)

Question 6

NADPH Production Associated w/ FA Synthesis (2 steps)

Answer 6

Cytosolic NADH-dependent malate dehydrogenase converts OAA to malate. NADP+ dependent malate dehydrogenase converts malate to pyruvate and creates NADPH from it

Question 7

2 Sources of Glycerol PO4 production in Liver

Answer 7

Dihydroxyacetone P from glycolysis converted via glycerol-P dehydrogenase
Glycerol converted via Glycerol kinase

Question 8

1 Source of Glycerol P Production in Adipose Tissue

Answer 8

DHAP from glycolysis converted via glycerol-P dehydrogenase

Question 9

TAG Synthesis (3)

Answer 9

Acyltransferases add to glycerol P twice until its phosphatidic acid
Phosphatase then removes PO4 so its diacylglycerol (DAG)
Acyltransferase then adds acyl so its triacylglycerol (TAG)

Question 10

Hormone-Sensitive Lipase

Answer 10

Activated by protein kinase from glucagon/epinephrine, breaks down TAGs

Question 11

Carnitine Shuttle (purpose and mech[2])

Answer 11

To transport LC FA-CoA from cyt to mt matrix without risk of synthesized FAs going right back in to matrix
Fatty acyl CoA transported to IM space, where carnitine palmitoyl-transferase I switches CoA for Carnitine
Then Fatty Acyl Carnitine transported to matrix, where carnitine palmitoyl transferase II switches back to Fatty Acyl CoA

Question 12

Beta Oxidation Rxns (4)

Answer 12

Oxidation of C2/3 yields double bond and produces FADH2
Hydration of double bond at C3
Oxidation of C3 hydroxyl, yielding NADH
Thiolysis w/ addition of CoA creating Acetyl CoA and Fatty acyl CoA (2Cs shorter)

Question 13

3 Products from Full Beta Oxidation of Palmitoyl CoA

Answer 13

7 FADH2, 7 NADH, and 8 Acetyl CoA

Question 14

Beta Oxidation of Odd-Number Chain FAs

Answer 14

Go through separate pathway where coenzyme form of Vit B12 eventually converts Methylmalonyl-CoA to Succinyl CoA for TCA cycle

Question 15

Ketone Body Synthesis (4)

Answer 15

FA Beta Oxidation yields Acetoacetyl CoA
HMG CoA Synthase adds another acetyl CoA to form HMG CoA
HMG CoA lyase removes acetyl CoA to form acetoacetate
3-Hydroxybutyrate dehydrogenase converts to 3-Hydroxybutarate

Question 16

Phospholipid Synthesis

Answer 16

CTP activates phosphatidic acid by adding CDP to diacylglycerol, and then an alcohol w/ head group can add

Question 17

Cleaving Points for the 4 Phospholipases

Answer 17

A1: C1 acyl group
A2: C2 acyl group
C: C3 after the O, before the P
D: C3 polar head group but leaves the P

Question 18

Phospholipase C Important Mech Involvement

Answer 18

Cleaves Phosphatidyl-inositol 4,5-bisphosphate to IP3 and DAG

Question 19

Niemann-Pick Disease (3)

Answer 19

Sphingomyelinase deficiency (sphingolipidosis)
Causes buildup of sphingomyelin and prevents ceramide release
Foamy appearing cells containing sphingomyelin under microscope

Question 20

Cerebroside

Answer 20

Ceramide w/ sugar residue

Question 21

Ganglioside

Answer 21

Cerebroside w/ charged COO- on terminal sugar

Question 22

Sulfatide

Answer 22

Cerebroside w/ OSO3- on terminal sugar

Question 23

Tay-Sachs Disease (4)

Answer 23

Sphingolipidosis
Beta-Hexosaminidase A deficiency
Causes accumulation of gangliosides (specifically NANA)
Prevents ceramide release

Question 24

Gaucher Disease (4)

Answer 24

Sphingolipidosis
Beta-glucosidase deficiency
Causes buildup of glucocerebrosides
Prevents ceramide release

Question 25

Prostaglandin Synthesis (4)

Answer 25

Dietary linoleic acid converted into arachidonic acid, which COX converts to PGG2 w/ 2 O2, and then peroxidase converts into PGH2, which differentiates into the different prostaglandins

Question 26

2 Fates of Arachidonic Acid

Answer 26

5-Lipoxygenase converts to Leukotrienes | COX-1 or 2 modify to PGG2

Question 27

2 Prostaglandins and Function

Answer 27

``` Thromboxane A2 (TXA2) promotes platelet aggregation Prostacyclin (PGI2) in endothelium of blood vessels, promoting vasodilation ```

Question 28

Aspirin Mech (3)

Answer 28

Acetylates serine side chain in COX active site, preventing prostaglandin synthesis Platelets don't have nuc, so TXA2 inhibition means they're done so blood thinning Endothelial cells can just degrade COX and make more, so PGI2 still fine

Question 29

Rate-Limiting "Gateway" into Cholesterol Biosynthesis

Answer 29

HMG CoA reductase converts HMG CoA to mevalonate

Question 30

Synthesis of Cholesterol Mevalonate->on (7)

Answer 30

6C mevalonate phopho'd twice to form 5-pyrophosphomevalonate Decarbox'd to isopentenyl pyrophosphate (IPP) (5C) Isomerized to dimethylallyl pyrophosphate (DPP) (5C) IPP added to form Geranyl pyrophosphate (10C) IPP added to form farnesyl pyrophosphate (15C) 2 of those form Squalene (30C) Then hydroxy added and other modifications to turn it into cholesterol

Question 31

Stimulation of HMG CoA Reductase Activity (2)

Answer 31

Phosphoprotein phosphatase dephosphoactivates it | SREBP also binds SRE, stimulating transcription of HMG CoA Reductase

Question 32

Inhibition of HMG CoA Reductase (2)

Answer 32

AMPK phosphodeactivates | Cholesterol inhibits SREBP release from Golgi

Question 33

Statins Action

Answer 33

Lower cholesterol my inhibiting HMG CoA Reductase

Question 34

Bile Acid Synthesis

Answer 34

Cholesterol 7-alpha-hydroxylase adds carboxylic acid to cholesterol alkane tail to for cholic acid or chenodeoxycholic acid

Question 35

Bile Salt Synthesis (2)

Answer 35

Glycine added to cholic acid to make glycocholic acid | Taurine added to chenodeoxycholic acid to make Taurochenodeoxycholic acid

Question 36

Enterohepatic Circulation

Answer 36

Bile salts/acids sent from liver/gallbladder to intestines and those that aren't excreted are recycled back to liver

Question 37

Steroid Synthesis (7 different molecules mentioned total)

Answer 37

Cholesterol to pregnenolone to progesterone which differentiates into cortisol, aldosterone, or testosterone (and then estradiol from there)

Question 38

Congenital Adrenal Hyperplasias (CAH)

Answer 38

Deficiencies in enzymes along the steroid hormone synthesis pathway

Question 39

General Passage of Cholesterol Through Lipoproteins (5)

Answer 39

Chylomicrons w/ lots of TAGs go from GI to muscles/tissues Remnants go to liver Contents repackaged into VLDL w/ some TAGs and cholesterol which goes to tissues LDL returns to liver w/ just cholesterol and cholesteryl esters HDL then secreted in bile, takes up cholesterol from peripheral tissues and returns

Question 40

Lipoprotein w/ Highest TAG component

Answer 40

Chylomicrons

Question 41

Lipoprotein w/ Highest Cholesterol Component

Answer 41

LDL

Question 42

Chylomicron Apolipoproteins (3 prots, 5 points)

Answer 42

Apo B-48 added upon nascent in SI Then C-II and Apo E added from HDL C-II activates lipoprotein lipase to hydrolyze TAGs to FAs and glycerol in capillaries Then Apo C-II returned to HDL from remnant Apo E binds to Rs in liver for endocytosis of the remnant

Question 43

VLDL and LDL Apolipoproteins (3 prots, 5 points)

Answer 43

Apo B-100 on nascent VLDL in liver Then Apo C-II and Apo E added from HDL Apo C-II activates lipoprotein lipase to hydrolyze TAGs to FAs and glycerol in capillaries Apo C-II and Apo E returned to HDL from LDL (which now has CEs and C almost entirely) Apo B-100 binds to LDL Rs on extrahepatic/liver tissues and are endocytosed

Question 44

Cholesteryl Ester Transfer Protein (CETP)

Answer 44

Catalyzes transfer of TAGs to HDL from VLDL and CE from HDL to VLDL

Question 45

Difference b/w Apo B-100 and Apo B-48

Answer 45

Come off same gene w/ same mRNA, but a cytosine is edited in ssRNA to create a stop codon to make Apo B-48 for chylomicrons

Question 46

Familial Hypercholesterolemia

Answer 46

Low LDL Rs causes hypercholesterolemia

Question 47

PCSK9

Answer 47

Gene for LDL R degrading protein on outside of the cell, new even more effective target for inhibition decreasing cholesterol

Question 48

2 Inhibitory Effects by Cholesterol

Answer 48

Blocks HMG CoA Reductase | Blocks synthesis of LDL Rs

Question 49

Cholesterol's Contribution to Arterosclerosis (major point and 4 steps)

Answer 49

Individual has to have high cholesterol *AND* unknown susceptibility to oxidative Endothelium causes/releases oxidative stress LDLs damaged by it Macrophages swallow damaged LDLs and become foam cells Foam cells deposit onto arterial walls causing plaques

Question 50

HDL Circulation

Answer 50

Released as bile and then has intermediate stages which pick up cholesterol from peripheral tissues and return to liver