Lecture 13

Question 1

Lipid Anabolism is ___ and where occurs

Answer 1

building up FA, basically the opposite of β oxidation happens in the cytosol

Question 2

Key intermediate in lipid anabolism (rate limiting step in FA synth)

Answer 2

Malonyl-CoA it is the rate limiting step in FA synthesis

Question 3

Answer 3

Maonyl-CoA

Question 4

Malonyl-coa synthesis

Answer 4

Basically carboxylating Acetyl-coa

biotin + HCO₃- + ATP → ADP + Pi + modified biotin w/ CO₂ → then we add Acetyl-CoA ⇒ malonyl-CoA

Question 5

Synthetase

Answer 5

has a T to it always uses ATP or ADP

Question 6

Synthase

Answer 6

no T so it doesn’t use ATP or ADP

Question 7

Overview of lipid anabolism

Answer 7

1. transport Ac-CoA from mitochondria to cytosol
2. sythesis of malonyl-coa
3. elongation (malonyl-coa pathway)
   
   1. condensation step
   2. reduction step
   3. deydration
   4. another reduction

Question 8

during condesation of malonyl coa synthesis ____ comes off as water, not CO₂

Answer 8

the double bond O

Question 9

Fattty acid synthesis done in

Answer 9

the liver

Question 10

Fatty acid synthase complex

Answer 10

enzyme does all four rxns to build FA

condensation, reduction, dehydration, reduction

2 landings with Sulfur (function like CoA)

Question 11

Acyl carrier protein function

Answer 11

Built in to FA complex:

carries acyl groups by thioester linkage

very similar to Co-Ash, they both have pantothenic acid

Question 12

Acetyl CoA carboxylase is mainly

Answer 12

• carboxylating Acetyl-CoA
• a biotin dependent carboxylation
• & spends ATP

Question 13

ACC

Substrates

Cofactors

Products

Answer 13

Acetyl-CoA carboxylase

Subs: Biotin + HCO₃ + ATP

Cofactors: biotin

Prod: Maolonyl CoA

Question 14

ACP

Answer 14

Acyl Carrier Protein in E. coli

similar to CoA

Question 15

Where in the cell does anabolic rxn occur?

Answer 15

cytosol

Question 16

NADPH sources

Answer 16

malic enzyme

pentose phosphate pathway

Question 17

main way to get NADPH is

Answer 17

pentose phosphate patway

Question 18

FAS in bacteria

Answer 18

7 activities in 7 separate polypeptides

Question 19

FAS in mammals

Answer 19

7 activities in one large polypeptide

Question 20

Main carbon source for anabolism (provides the building blocks)

Answer 20

Citrate!

when it is abundant it leaves the mitochondria → cytosol and gets cleaved into OAA and Acetyl-CoA which are used in anabolism

Question 21

Minor source of NADPH for anabolism

Answer 21

Malate

malic enzyme takes malate → Pyr (which is used to make more NADPH)

Question 22

____ is an allosteric inhibitor of carnitine Palmitoyl-CoA

Answer 22

malonyl-CoA

Question 23

____ will activate FAS through malonyl-coa

Answer 23

Citrate

Question 24

hormonal regulation of FAS

Answer 24

glucagon, epinephrine, block synthesis and increase degredation of FA

Question 25

Fatty acid synthesis location in the cell

Answer 25

cytosol

Question 26

Fatty acid oxidation location in the cell AKA ß oxidation

Answer 26

matrix

Question 27

Key rxns to modify FA

Answer 27

elongation and desaturation

Question 28

essential FA that we must consume

Answer 28

omega 3 FA Omega 6 FA complex polyunsaturated Made by plants, which we consume and use for other things

Question 29

Linoleate

Answer 29

Essential FA made by plants only

Question 30

arachidonate

Answer 30

Derived from linoleate--an omega-6 precursor for important molecules: COX

Question 31

arachidonic acid are oxidizer molec that make

Answer 31

physiologcal regulatiors: **prostaglandins & thromboxanes**

Question 32

respponsible for controling inflamation, smooth muscle contraction, uterine function, gastric function...

Answer 32

prostaglandins and thromboxanes---super responsive

Question 33

COX

Answer 33

cycloxigenase

Question 34

Aspirin covalently bonds to ____ of COX

Answer 34

serine part of COX

Question 35

covalent inhibitor or COX

Answer 35

aspirin

Question 36

prostaglandins are

Answer 36

chemicals that promote inflamation, pain and fever

Question 37

NSAID's

Answer 37

Non-Steroidal Anti- Inflamatory Drugs acetominophen aspirin ibuprofen naproxen

Question 38

isozymes meaning

Answer 38

two differnet versions of an enzyme, encoded from different genes. have a common ancestor

Question 39

involved in normal gastric function

Answer 39

COX 1

Question 40

involved in inflamation and fever

Answer 40

COX 2

Question 41

why does taking antiinflamatory does cause gastric bleeding?

Answer 41

becuase if enough drug (which should inhibit COX2) is taken, it also starts inhibiting COX1 causing bleeding.

Question 42

COX-2 specific inhibitions

Answer 42

colecoxib rofecoxib

Question 43

Vioxx

Answer 43

a COX2 specific inhibitor (rofecoxib) that causes rare cardiac problems. the drug that Merck made

Question 44

"on pathway, off pathway"

Answer 44

inhibiting one thing can inhibit other things in the way

Question 45

Isoprenes

Answer 45

branched lipid structure used to make sterols (eg: cholesterol)

Question 46

Answer 46

basic Isoprene structure

Question 47

Answer 47

HMG-CoA

Question 48

4 stages in cholesterol synthesis

Answer 48

1. mevalonate production 2. conversion to active isoprenes 3. condensation of isoprenes, conversion to squalene 4. conversion to cholesterol

Question 49

Mevalonate production rxns

Answer 49

acetyl-coa → acetoacetyl-coa → HMG-CoA → mevalonate

Question 50

mevalonate production occurs where

Answer 50

cytosol

Question 51

competivie inhibitors of HMG-CoA reductase

Answer 51

**statins** they are rate limiting enzyme for cholesterol synthesis

Question 52

commitment step of making isoprenes

Answer 52

synth of mevalonate

Question 53

low density lipoprotein

Answer 53

LDL: a way to send insoluble things into bloodsteam (which is basically water)