Biochemistry Ii Test 2

Front 1

What is cancer?

Back 1

A group of diseases with a loss of growth control

Front 2

Genes that are activated in cancer

Back 2

Proto-oncogenes

Front 3

Genes that are deactivated in cancer?

Back 3

Tumor suppressors

Front 4

How is gene expression altered in canceer?

Back 4

Mutations

Front 5

morecell divisions more mutations in proto-oncogenes & tumor suppressor genes
What process in cancer?

Back 5

Proliferation

Front 6

Invasionof surrounding tissue in cancer cells

Back 6

Carcinoma in situ

Front 7

Can cancer invade blood vessels?

Back 7

Yes

Front 8

What happens after cancer invades the bloodstream?

Back 8

Metastasis

Front 9

Becausethey have lost ______ control, cancer cells can grow in culture

Back 9

growth

Front 10

Criteria for cancer to grow in culture (3)

Back 10

1. reduced dependence on serum
2. anchorage independence (growth in softagar)3. tumor forming when injected into mice

Front 11

Anchorage independence allows cancer to grow on what type of media?

Back 11

Soft agar

Front 12

New growth

Back 12

Neoplasm

Front 13

tumorthat originates from epithelial cells

Back 13

Carcinoma

Front 14

gland like cancer of epithelial cells

Back 14

Adenocarcinoma

Front 15

Consumedin food
Madein the stomach from nitrites in preservatives(curedmeats)

Back 15

Nitrosamine

Front 16

Nitrosamine is consumed how?

Back 16

In foods with nitrites in preservatives, likeccured meats

Front 17

Producedfrom amines found in fish (salt cured)highgastriccancer rates in Japan, Iceland
This is a result of what?

Back 17

DNA mutations by nitroasmine

Front 18

Pairswith thymine in DNA replication instead of C in nitrosamine

Back 18

Methylated guanine

Front 19

in nitroasmine DNA mutations, what is methylated guanine pairs with _______ in DNA replication instead of ________

Back 19

thymine, cytosine

Front 20

What structures/compounds are formed by nitrosmine-indued mutations in DNA (2)?

Back 20

Methylated guanine

Benzo-a-pyrene

Front 21

canbe considered tumor suppressor genes
Mutationsin them increase mutationrate
What enzymes?

Back 21

DNA repair enzymes

Front 22

DNA repair enzymes involved in breast cancer development

Back 22

BRACA1, BRACA2

Front 23

HNPCC causes colon cancer by what type of mutations?

Back 23

Mismatch repair mutations

Front 24

Causes colon cancer by mismatch repair mutations

Back 24

HNPCC

Front 25

Increasedexpression: Promoterleads toIncreasedProtein Activity
This is done by what substances (2)?
What genes do they act on?
What type of mutation is this?

Back 25

Radiation, chemical carcinogens.

Proto-oncogenes

Gain-of-function

Front 26

Generearrangement stronger promoter, enhancer or fused to another gene creating a fusion protein
What type of gene does this happen to in cancer?
What type of mutation is this?

Back 26

Proto-oncogenes

Gain-of-function

Front 27

Geneamplification
Multiple proto-oncogene copies
What tyep of mutation is this in cancer?

Back 27

Gain-of-function

Front 28

erb-b2 and N-myc are what types of genes?

Back 28

Proto-oncogenes

Front 29

erb-b2

What type of gene?

What type of cancer is it seen in?

Back 29

Proto-oncogene

Some breast cancers

Front 30

N-myc

What type of gene?

What type of cancer is it seen in?

Back 30

Proto-oncogene

Some neuroblastomas

Front 31

Viruses that insert into a genome activate what type fo genes?

Back 31

Proto-oncogenes

Front 32

Virus taht inserts into a genome leads to what type cancer?

Back 32

Burkitt lymphoma

Front 33

Viruses that enter into the genome can create _________ or increase tehir expression?

Back 33

Oncogenes

Front 34

MicroRNAscan act as _________ if they decrease expression of a gene that limits cell proliferation

Back 34

oncogenes

Front 35

Ligands for growth factor receptors.

They can be over or underexpressed in cnacner?

Back 35

Growth factors.

Overexpressed

Front 36

usuallyin plasma membrane can become independent of the Growth factor in cancer
What protein?

Back 36

Growth factor recptors

Front 37

What type of protein is Ras?

Back 37

Signal transdution protein

Front 38

G-protien

GTP-ase activity

Proto-oncogene or tumor suppressor?

Back 38

Ras

Proto-oncogen

Front 39

Which Ras form is active and activates teh kinase cascade?

Back 39

Ras-GTP

Front 40

Which Ras form is inactive ?

Back 40

Ras-GDP

Front 41

Mutationin ______activity means Ras isalways on
what type of gene is this once mutated?

Back 41

GTPase

Oncogene

Front 42

Ras activates ___, a Ser-Thr kinase

Back 42

Raf

Front 43

Ras activates Raf, a ___-___ kinase

Back 43

Ser-Thr

Front 44

Raf AKA

Back 44

MAP Kinase Kinase Kinase

Front 45

MAP AKA

Back 45

Mitogen Activated Kinase

Front 46

MEK AKA

Back 46

MAP Kinase Kinase

Front 47

MEK activates what protein?

Back 47

Map Kinase

Front 48

Nuclear acitve protein activated by Map Kinase

Back 48

AP-1

Front 49

AP-1 phosphorlyates transcription factors that activate what proto-oncogenes (2)

Back 49

myc
fos

Front 50

Phosphorylationcauses __________ in the Ras-MAPK pathway
Any of the genes in the cascadecould become _________ through activating mutations

Back 50

activation

oncogenes

Front 51

Transcriptoin factor.

Activated by translocation.

In the nucleus.

Cauess Acute T-Cell Leukemia

What gene?

Back 51

Hox11

Front 52

Transcription factor

Activated by translocation.

In the nucleus.

Cauess Burkitt Lymphoma.

Also activated by amplification

In the nucleus.

Causes Neuroblastoma or Small Cell Lung Carcinoma.

What gene?

Back 52

myc

Front 53

Transcription factors.

Activated by phosphorlyation.

In the nucleus.

Caues osteosarcoma or sarcoma.

What genes (2)

Back 53

fos, jun

Front 54

Each ______ Activates expressionof thenext one

Back 54

cyclin

Front 55

Proteins that activate teh cell cycle and allow it to progress

Back 55

Cyclins

Front 56

Phases of teh cell cycle, starting with G0

Back 56

G0

G1

S

G2

M

Front 57

Cyclin that increases throughout G1, stops at S

Back 57

Cyclin D

Front 58

Cyclin that increases through the first half of S phase

Back 58

Cyclin E

Front 59

Cyclin that increases throughout all of S phase, sotps at G2

Back 59

Cylcin A

Front 60

Cyclin that increases throughout G2, Stops at M

Back 60

Cyclin B

Front 61

Cyclin expression by cell cycle.

Name them all

Back 61

G1- D

S- E, A

G2- B

Front 62

Cyclinproteins are degraded by ___________ socellcycle can continue

Back 62

proteolysis

Front 63

Cyclin Dependent Kinases are only active when bound to teh correct ______

Back 63

yclin

c

Front 64

Inhibit CDK activity

Back 64

Cyclin-Kinase Inhibitors

Front 65

Cip/Kip(e.g. p21)
Protein type?
Activity?

Back 65

Cyclin-Kinase Inhibitors

Inhibit CDK activity

Front 66

INK4

What tyep of protien?

Activity?

Specificially, what protein does it act on?

Back 66

Cyclin-Kinae INhibitor

Inhibits CDK activity

Cyclin-D

Front 67

___ is induced in response ToDNA damageStopscell cycle so repairCanoccur before progressing

Back 67

P21

Front 68

P21is induced in response To ___ ______
Stopscell cycle so repairCanoccur before progressing

Back 68

DNA damage

Front 69

Can a cell go back into G1 phase after it enters S?

Why or why not?

Back 69

No!

Its gone through teh G1-S Checkpoint

Front 70

G1-S Checkpoint proteins (5)

Back 70

Cyclin D, Cdk4, Cdk6, Rb, E2F

Front 71

CD4 phosphorlyates what protein?

Back 71

Rb

Front 72

Phosphorlyates Rb

This allows what protein to enter the nucleus and induce transcription?

Back 72

CD4
E2F

Front 73

CD4phosphorylates __
___ is free to bindDNAand activate genes required for DNA synthesis:CyclinE & Cyclin A(which bind ____), cdc25A
Originbinding proteins

Back 73

Rb

E2F

Cdk2

Front 74

Cyclins that bind CDK2 (2)

Back 74

Cyclin E

Cyclin A

Front 75

How are mutations in teh Rb gene usually acquired?

Back 75

They are inherited

Front 76

Inherited genes AKA

Back 76

Familal genes

Front 77

Muchless frequent
Mutationsin both copies
Haveto occur in the same celltoget inactivation
Which type of inheritance of Rb mutation?

Back 77

Sporadic

Front 78

Sporadic inheritance of Rb mutation:

Much ____ frequent
Mutationsin ____ copies
Haveto occur in the ____ ____toget inactivation

Back 78

less

both

same cell

Front 79

bornwith one mutation
Any cell that gets a second mutation
will develop retinoblastoma
100% chance
Occurs in childhood
What gene?
Which inheritance pattern?

Back 79

Rb, Familal

Front 80

___ Regulates cell division and apoptosis

Back 80

P53

Front 81

50%of human tumors have inactivated ___ (both copies)

Back 81

p53

Front 82

Haltsreplication in cells with DNA damage
What protein?

Back 82

p53

Front 83

Cellswith Unrepaired DNA are targeted for apoptosis (programmed cell death) by increased __expression

Back 83

BAX

Front 84

Apoptosis

Back 84

Programemd cell death

Front 85

P53 activatestranscription of ___ (Kip/Cip family) and ______

Back 85

p21, GAAD45

Front 86

Protein family of p21

Back 86

Kip/Cip

Front 87

P53 activatestranscription of p21 (Kip/Cip family) and GADD45 (Growth arrest and DNA damage)
Prevents ___ activation and __phosphorylation

Back 87

CDK, Rb

Front 88

IfDNA is repaired, p53 activates ____ expression & is downregulated by ____

Back 88

mdm2, mdm2

Front 89

NF-1 can lead to what condition?

Back 89

Neurofibramatosis

Front 90

Neurofibrominmutant cells
Have activated ___
Neurofibromatosisdevelops

Back 90

Ras

Front 91

Neurofibrominmutant cells
Have activated Ras
_________________ develops

Back 91

Neurofibramatosis

Front 92

Nervous specific GAP

Back 92

Neurofibromin

Front 93

GAP AKA

Back 93

GTPase Activating Protein

Front 94

Neurofibromin inhibits ___

Back 94

Ras

Front 95

What organism was patched-Smoothened discovered in?

Back 95

Drophilia

Front 96

Patched- Gene type?

Smoothened- Gene type?

Back 96

Tumor-suppressor

Proto-Oncogene

Front 97

Patched and smoothened are co-receptors for what protein?

Back 97

Hedgehog

Front 98

Protein that congrols growth during embryogenesis

Back 98

Hedgehog

Front 99

Patched inhibits ___________

Back 99

Smoothened

Front 100

_______ inhibits smoothened

Back 100

Patched

Front 101

Patchedinhibits Smoothened
________ binding releases inhibition

Back 101

Hedgehog

Front 102

Increasedincidence of Basal cell carcinoma ifPatchedis ___________ OR ifSmoothenedis _________

Back 102

inactivated, activated

Front 103

Increasedincidence of _____ ____ __________ ifPatchedis inactivated OR ifSmoothenedis activated

Back 103

basal cell carcinoma

Front 104

Proteins involved in cell adhesion and can act as tumor suppressors (2)

Back 104

Catenins

Cadherins

Front 105

A.Cellsattach to each other through _________

Back 105

Cadherins

Front 106

Cadherins are dependent on what molecule?

Back 106

Calcium

Front 107

Cadherins are anchored by ________ insidethe cell
They bindto _____ ________

Back 107

cateenins

actin filaments

Front 108

What makes up the cytoskeleton?

Back 108

Actin filaments

Front 109

Β.b- Catenins can also activate ______________!

Back 109

transcription

Front 110

beta-catenins are bound to ___

Back 110

APC

Front 111

APC AKA

Back 111

Adematous Polyposis

Coli

Front 112

APC is degraded releasing _-__________

Back 112

b-catenins

Front 113

APCis degraded releasing b- Catenins
Translocated to nucleus and activate transcription ___ and _______ _

Back 113

myc, cyclin D

Front 114

What type fo gene is APC?

Back 114

Tumor suppressor

Front 115

Can mutated APC bind to beta-catenins?

Back 115

No

Front 116

APC is inherited in most of what type of cancer?

Back 116

Colon

Front 117

Inherited APC mutation leads to what conditon?

Back 117

Familial adenamatous polyposis

Front 118

Review Apoptosis pathways (intrinsic & extrinsic)

Back 118

DO IT!

Front 119

Bcl-2 protein leads to what?

Back 119

Increased permeability of the mitochondrial membrane

Front 120

Protein that leads to increaesd permeability fo the mitochondrial membrane

Back 120

Bcl-2

Front 121

Antiapoptotic members of teh BCL-2 family?

Back 121

Bcl-2

Bcl-x

Bcl-w

Front 122

Pro-apoptotic members of the Bcl-2 family?

Back 122

Bax

Bak

Box

Front 123

Pro-apoptotic BH3 only members of teh Bcl-2 family (3)

Back 123

Bad

Bid

Bim

Front 124

Growth factor independence in cancer cells is due to a mutation in what gene?

Back 124

Ras

Front 125

______ cells bypass apoptosis

Back 125

Cancer

Front 126

Growthfactor dependent anti-apoptosis pathways
PDGF/Akt/Bad pathway: ___-_ cannot induce apoptosis
Normal cells undergo apoptosis without ______ ______!

Back 126

Bad-P

Growth factors

Front 127

Bcl-2mutation and increased expression is common in what kind of cells?
Why?

Back 127

Cancer

It is anti-apoptotic

Front 128

______ ____ control Bcl-2 expression

Back 128

Micro RNAs

Front 129

MicroRNAs control ___-_ expression

Back 129

BCL-2

Front 130

Normal colonic epithelium

Loss of APC

__________________ epithelium

_____ _______

Activation of Ras

____________ _______

Loss of a tumor-suppressor gene

____ ________

Loss of p53 Function

__________

Other alterations

__________

Back 130

Hyperproliferative

Early adenoma

Intermediate Adeoma

Late Adenoma

Carcinoma

Metastasis

Front 131

Smad4/DPC & TGF-b mutations are seen in what cancer?

Back 131

Colon Cancer

Front 132

VHL is mutated in what type of cancer?

Back 132

Kidney

Front 133

Braca1 and Braca2 are seen in what cancer?

Back 133

Breast cancer

Front 134

Patched and smoothened are seen in what cancers?

Back 134

Basal cell carcinoma

Front 135

Blood lipoprotein produced in intestinal epithelil cells from dietary fat.

Carries TAG in blood

Back 135

Chylomicron

Front 136

Blood lipoprotein produced in liver mainly from dietary carbs. Carries TAGs in the blood

Back 136

VLDL

Front 137

Blood lipoprotein produced in blood

Remnant of VLDL after TAG digestion

Endocytosized by liver or converted to LDL

Back 137

IDL

Front 138

Blood lipoprotein produced in blood
Remnant of IDL TAG digestion, end product of VLDL
Contains high concentration of cholesterol and cholesterol esters
Endocytized by liver adn periopheral tissues

Back 138

LDL

Front 139

Blood lipoprotein produced in liver and intestine.
Exhcnages proteins and lipids with other lipoproteins
Functions in return of cholestrol from peripheral tissues to the liver

Back 139

HDL

Front 140

VLDL AKA

Back 140

Very Low Density Lipoprotein

Front 141

IDL AKA

Back 141

Intermediate Density Lipoprotein

Front 142

LDL AKA

Back 142

Low-Density Lipoprotein

Front 143

HDL AKA

Back 143

high-density Lipoprotein

Front 144

3Fatty acyl groups bonded to glycerol through ester bond

Back 144

Triacylglycerols

Front 145

Do fatty acyl grops have to be identical in TAG?

Back 145

No

Front 146

C2 of TAG is usually saturated or unsaturated

Back 146

Unsaturated

Front 147

Sizes of FA's that can be incorporated into TAGs

Back 147

Medium

SHort

Long

Very long

Front 148

breakfatty acids from glycerol backbone at C1 & C3

Back 148

Lipases

Front 149

importantfor infants to digest FA in milk (2 enzymes)

Back 149

Lingual Lipase

Gastric Lipase

Front 150

Major intestinal lipase results in what product?

Back 150

2-monoacylglycerol

Front 151

long chain polyunsaturated FA
importantfor brain development
Seen in what type of milk

Back 151

Human

Front 152

mostly short and medium chain FA
doesn’tcontain long chain polyunsaturated FA
What type of milk?

Back 152

ow

C

Front 153

Infants have very little __________ lipase

Instead they rely on _______ and _______

Back 153

intestinal

lingual, gastric

Front 154

human milk has lipases that survivethe _______ and are active in the _________

Back 154

stomach, intestine

Front 155

at type of milk has lipases that are survive the stomach adn move to the intestine

Wh

Back 155

Human

Front 156

•The bulk of dietary lipids consumed are _____________
•Foods also contain phospholipids,sterols like ___________ andmany minor lipids, including ___-soluble vitamins
•triglyceride absorption requires threeprocesses
1._____________
2. Hydrolysis to ________________and _____ _____
3. Transport of monoacylglycerol and fatty acids into ___________
•____ _____ and __________ ______ key molecules for digestion of lipids inthe intestine

Back 156

triacylclycerols

cholesterol, fat

Emulsificaiton

monoacylglycerol, fatty acids

enterocytes

Bile acids, pancreatic lipase

Front 157

Bile acids are synthesized where?

From what?

Secretedinto intestine via gall bladder onresponse to _______________ hormonesecreted by __________ cells

Back 157

Liver

Cholesterol

Cholecystokinin, intestinal

Front 158

___________ moleculesForman interface between polar and non-polar substances
Actas detergents: bind ___ globules asthey are broken up by peristalsis.Emulsifiedfat has _______ surface area so _______ have access.
Micelles: _____ outside___________ inside

Back 158

Amphipathic

fat

greater, lipases

polar, hydrophobic

Front 159

Intestinalhormones_______________ and ________•Secretintriggers ___________ release From pancreas, liver, intestinal cells
•Cholecystokinin triggers ________ secretion from pancreas with ________

Back 159

cholecystokinin, secretin

bicarbonate

lipase, colipase

Front 160

Bilesalts inhibit ______
_________ bindslipase and __ so __ can enter the active siteHydrolyzesFA (all sizes) from __ & __Free __ and ________________

Back 160

lipase

Colipase, FA, FA, C1, C3

FA, monoacylglycerol

Front 161

removesFA from cholesterol
released from what organ?

Back 161

Pancreatic esterase

Pancreas

Front 162

removesFA from phospholipids
Released from what organ?

Back 162

Phospholipase A2

Pancerase

Front 163

FFAand 2 monoacylglycerol mustbe packagedInto ________ with bile salts
Critical _______ Concentration (___) of ____ _____ is _-__ mM
_____ this concentration, no micelles form
Micellesare mixed: ___, ___________, ____________________________, ___ soluble vitamins

Back 163

micelles

Micelle, CMC, bile salts, 5-15

FFA, cholesterol, lysophospholipids, fat

Front 164

Which part of the micelle is absorbed?

Which part is recycled?

Back 164

lipids components.

Bile Salts

Front 165

______ & ______ chain FA don’t requiremicelles

Back 165

Short, medium

Front 166

How are short and medium chain FA's absorbed?

Back 166

Directly by Intestinal Epithelial cells

Front 167

How are long chain FA's and 2-monoacylglycerols absorbed into cells?

Back 167

Transported in micelles

Absorbed into Intestinal epithelial cells

Reassembled into Triacylglycerols

Packaged into chylomicrons

Front 168

Triacylglycerols in teh IEC are packaged into ____________ along with which apolipoprotein?

Back 168

chylomicrons

ApoB48

Front 169

Chylomicrons go form teh intestinal epithelial cells into teh _________ ________ and then into the _____

Back 169

lymphatic lacteals

blood

Front 170

Bilesalts are recycled
Absorbedin the _____

Back 170

ileum

Front 171

Bilesalts are recycled
Absorbedin the _____
Carriedto _____ through _____________circulationReturnedto ____ _______
Lessthan _% are excreted Inthe feces

Back 171

ileum

liver, enterohepatic

gall bladder

5

Front 172

How are FA's activated to synthesize TAGs?

Back 172

Acyetlated by Acetyl-CoA

Front 173

What % of chylomicrons are made up of TAGs?

Back 173

85%

Front 174

Chylomicrons are laregly made of what?

Back 174

Triacylglycerols

Front 175

TG are syntehsized where?

Back 175

Smooth Er

Front 176

Where is ApoB48 synthesized?

Back 176

Rough ER

Front 177

Where does the assembly of lipoproteins occur (2)?

Back 177

ER, Golgi

Front 178

Chylomicrons are sent to the _____ of lymphatics, and then to teh _____, via ___________

Back 178

chyle, blood, exocytosis

Front 179

B-apoprotein ____ is edited in the instienal cell

Back 179

mRNA

Front 180

B-apoprotein mRNA is edited where?

Back 180

Intestinal cells

Front 181

Nascent chylomicrons pick up proteins from HDL to become ______ _____________

Back 181

mature chylomicrons

Front 182

Nascent chylomicrons pick up fproteins from ___ to become mature chylomicrons

Back 182

HDL

Front 183

recognizedby membrane receptors (esp.liver) lipidsenter by endocytosis

Which Apoprotein found on mature chylomicrons?

Back 183

Apo E

Front 184

Activateslipoprotein lipase oncapillary endothelial cells (esp.muscle & adipose tissue)

Which apoprotein foudn on mature chylomicrons?

Back 184

ApoCII

Front 185

Lipoprotein Lpiase on the endothelial cell surface removes FA from _____________ and ___

Back 185

chylomicrns, VLDL

Front 186

Chylomicron remnants are taken up by the liver via which apoprotein?

Back 186

ApoE

Front 187

Which Apo allele is strongly associated with Alzhimers?

Back 187

APOE4

Front 188

___________ ______ on surface of endothelial cells removes FA from chylomicrons and VLDL

Back 188

Lipoprotein Lipase

Front 189

Liver, Lactating mammary glandskidney lungs brain
ALl of these are organs involved in what process?

Back 189

Fatty acid synthesis

Front 190

Structure of a phospholipid

Back 190

Glycerol backbone

3C

C1 = FA

C2 = FA

C3 = Phosphate Group + Head Group

Front 191

Plasmologen Structure

Back 191

Glycerol Backbone

3 C

C1 = DB - Ether linkage to a VLCFA

C2 = FA

C3 = Phosphate Group - Head Group

Front 192

Ceramide Structure

Back 192

Sphingosine Backbone

C2 = FA

C3 = Phspate Group - Choline

Front 193

Glycolipid Structure

Back 193

Sphingosine Backbone

C2 = FA

C3 = O - Carbohydrate

Front 194

Initial substrate of FA synthesis

Back 194

Acetyl-CoA

Front 195

What determines the fate of pyruvate inside the mitochondrial matrix?

Back 195

Concentration of Acetyl CoA

Front 196

If Acetyl CoA is ____,PDH is inhibited
Pyruvate converted to ___

Back 196

high

OAA

Front 197

If Acetyl CoA is high, ___ is _________
Pyruvate converted to OAA

Back 197

low, PDH

Front 198

If Acetyl CoA is high,PDH is inhibited
________ converted to ___

Back 198

Pyruvate, OAA

Front 199

Converts pyruvate to OAA in the mitochondira?

Convertes pyruvate into Acetyl-CoA in the mitochondria?

Back 199

Pyruvate Carboxylase

Pyruvate Dehydrogenase

Front 200

Acetyl-CoA is trasnferred from mitochondria to cytosol as what molecule?

Back 200

Citrate

Front 201

Enzyme that converts cytosolic citrate to OAA and Acetyl-CoA

Back 201

Citrate Lyase

Front 202

Citrate Lyase converts _______ to ___ and ______-___

Back 202

citrate, OAA, Acetyl-CoA

Front 203

IsocitrateDehydrogenase is inhibited by ___

Back 203

ATP

Front 204

Isocitrate dehydrogenase is inhibited by what molceules (2)

Isocitrate dehdrogenase is activate dby what molecule?

Inhibition of this enzyme leads to buildup of what molecules in teh mitochondria (2)?

Back 204

ATP, NADPH

ADP

Citrate, Acetyl-CoA

Front 205

Isocitrate dehydrogenase activity?

Back 205

Isocitrate to alpha-ketogluterate

Front 206

Most important regulated step in teh TCA Cycle

Back 206

Isocitrate dehydrogenase

Front 207

Citrate in teh cytosol is cleaved to re-form what molceules?

Back 207

OAA

Acetyl-CoA

Front 208

Citrate -(Citrate Lyase)-> OAA

OAA goes is reduced to what?

By what enzyme?

Back 208

Malate

Malate dehydrogenase

Front 209

Malate dehydrogenase enzyme converts what to what?

Back 209

OAA to malate

Front 210

Malate dehydrogenase enzyme uses what cofactor?

Back 210

NADH

Front 211

Malic acid decarboxylates what to what?

Back 211

Malate to pyruvate

Front 212

How is malate converted to pyruvate?

What cofactor is used?

Back 212

Malic enzyme (decarboxylated)

NADP+ is converted to NADPH

Front 213

Malic enzyme AKA (2 names)

Back 213

Decarboxylating enzyme

NADPH-dependent malate dehydrogenase

Front 214

ces of NADPH for FA synthesis (2)

Sour

Back 214

Pentose Phosphate Pathway

Malic Enzyme

Front 215

PDH

Malic Enzyme

Glucose 6P Dehydrogenase

All are stimulated by high or low insulin:glucagon ratio?

Back 215

High

Front 216

Denovo synthesis of fatty acids is a _________process:
involves _____ major stages

Back 216

cytosolic

3

Front 217

3 basic steps of FA synthesis

Back 217

1. Transport of Acetyl-CoA from mitochondria to cytosol

2. Conversion of Acetyl-CoA to malonyl CoA

3. Conversion of Acetyl-CoA and Malonyl-CoA to FA via steps of multienzyme FAS comples

Front 218

Fatty Acid Synthase AKA

Back 218

FAS

Front 219

AcetylCoA donates _C to form Malonyl CoA

Back 219

2

Front 220

Malonyl CoA has how many C's?

Where do they come from?

Back 220

3

2 from Acetyl-CoA

1 from CO2

Front 221

Enzyme + Cofactors (2) needed for conversion of Actetyl-CoA to Malonyl CoA

Back 221

Acetyl-CoA Carboxylase

Biotoin

ATP

Front 222

Rate limiting stepf of FA Syntehsis

What does it do?

Back 222

ACC

Converts Acetyl-CoA to Malonyl CoA

Front 223

Phosphorlyation or allosteric modification of ACC leads to alterted biosynthesis of what?

Back 223

Fatty Acids

Front 224

Pyruvate carboxylase has what as a cofactor?

Back 224

Biotin

Front 225

Activated form of ACC
Inactive?

Back 225

ACC

ACC-P

Front 226

Insulin activates Acetyl-CoA Carboxylase Phosphatase or Kinase?

Back 226

Phosphatase

Front 227

Insulin activates or represses FAS and ACC?

Back 227

Activates

Front 228

Citrate activates or inhibits ACC?

How?

Back 228

Activates

Allosteric Subunit Polymerization

Front 229

AMP Activated Protein Kinase activates or inhibits ACC?

Back 229

Inhibits

Front 230

AMP-dependent protein kinase is more dependent on ATP-ADP ratio or ATP-AMP ratio?

Back 230

ATP-AMP

Front 231

Palmitoyl-CoA Activates or inhibits ACC?

How/why?

Back 231

Inhibits
Product inhibition

Front 232

Acyl-Carrier Protein AKA

Back 232

ACP

Front 233

ACP is linked to FAS ______

Back 233

serine

Front 234

Pantethenic Acid AKA

Back 234

Vitamin B5

Front 235

Phosphopanetheine is a precursor to what?
What is it derived from?

Back 235

Pantethenic Acid

CoA

Front 236

In FAS, how many C's are added at a time?

Where do they come from?

What cofactor is required?

Back 236

2

Malonyl-CoA

NADPH

Front 237

What is FAS composed of (think subunits) ?

Back 237

2 identical subunites

Homodimers

Front 238

How many enzyme activiteis of FAS?

Back 238

7 + ACP

Front 239

Second Acyl Binding site on FAS?

Back 239

Cysteine on FAS

Front 240

ACP ends in what group?
What attaches here?

Back 240

Sulfhydryl group

Malonyl-CoA

Front 241

Which site of ACP is the acyl binding site of malonyl?

Back 241

P

Front 242

ACP ends in what gropu?

What attaches here?

Back 242

Sulfhydryl

Malonyl CoA

Front 243

Cysteinyl group in FAS

What attaches here?

Back 243

S

Acetyl

Front 244

In FAS:
Malonyl ________ condenses with carbonyl carbonAcetylgroup now attached to ___ site
___ is released
_ carbons are added to carboxyl end
4carbon b-keto acid now on the ___ site

Back 244

carboxyl

ACP

CO2

2

ACP

Front 245

FAS:
1.Reductionof b-keto acyl group to ________ by _____
2._____removal formsa doublebond
3.Reduction ofthe double bond by _____
Transferof the 4 carbon acyl chain to ________ site
NewMalonyl group binds to ___ site

Back 245

hydroxyl, NADPH

Water

NADPH

cysteinyl

ACP

Front 246

FAS summary:
1.Malonyltransfer to ___ site
2.Condensation& loss of ___
3.Reductionof b-keto group to ___
4.______ ____ forms
5.ReductionTransferto ________ site

Back 246

ACP

CO2

-OH

Double bond

Cysteinyl

Front 247

EachRound of FAS Reactions adds _ more C tothe growing acyl chain until it’s__ carbons long
Then hydrolysis from ___

Back 247

2

16

ACP

Front 248

Malonyl CoA ________ CPT1

Back 248

Inhibits

Front 249

CPT1 is inhibited by what molecule?

Back 249

Malonyl CoA

Front 250

CPT1 AKA

Back 250

Carnitine Plmitoyl Transferase

Front 251

________ ___ inhibits ____
Preventsa fatty acid futile cycle

Back 251

Malonyl-CoA, CPT1

Front 252

Acetyl-CoA to malonyl coa reaction is done by what enzyme?

Back 252

Acetyl-CoA carboxylase

Front 253

Where does elongation fo palmitate or FA's happen?

Back 253

ER

Front 254

Palmitate activated by CoA

Back 254

almitoyl-CoA

P

Front 255

Paomitoyl-CoA is elongated how many C's at a tiem?

What donates the C's & what is released?

What cofactor is reduced?

Palmitate elongation is similar to FAS, except Acyl chain is attached to what molecule rather than ACP?

Back 255

2

Malonyl CoA, CO2

NADPH

CoA

Front 256

Palmitoyl CoA elongation main reaction?

Back 256

Palmitoyl-CoA to Steratoyl CoA

Front 257

Steratoyl CoA C length?

Back 257

18C

Front 258

How many C's in a VLCFA?

Back 258

22-24

Front 259

22-24 C'sa re seen in what type of FA?

Back 259

VLCFA

Front 260

VLCFA's are expecially in what organ?

Back 260

Brain

Front 261

Where does desaturation of Fatty acids take place?

Back 261

ER

Front 262

Desaturation of fatty acids in the ER use what molecule?

WHat substrates are oxidized (2)

Back 262

Molecular Oxygen

Fatty Acid, NADH

Front 263

Desaturation of FA's.

Products?

Back 263

Water

Monounsaturated Fatty acyl CoA

Front 264

Human desaturases only work on C_ adn below

m < _

Back 264

9

7

Front 265

Essential Polyunsaturated Fatty Acids AKA

Back 265

PUFA

Front 266

Most common essential PUFA

Back 266

Palmitate (18) --> Palmitoleic Acid (18:1)

Front 267

Palmitate C formula

Back 267

16:0

Front 268

Palmitoleic Acid C Formula

Back 268

16:1 delta 9

Front 269

Stearic C Formula

Back 269

18:0

Front 270

Oleic C Formula

Back 270

18:1 delta 9

Front 271

Palmitate is desaturated to form what molecule?

Back 271

Palmitotieic Acid

Front 272

Sterate is desaturated to form what molecule?

Back 272

Oleic

Front 273

Can humans desaturate C5?

C6?

C12?

Back 273

Yes

Yes

No

Front 274

Human desaturases only work on C_ and below

m < _

Back 274

9

7

Front 275

Requirements for eicosanoid syntheseis (3)

Are tehse essential or non-essential?

Back 275

3 (double bonds 3 from teh end) = essential

Linoleic Acid = essential

3-linoleic acid = essetial

Front 276

Linoleic Acid C formula

Back 276

18:2 delta 9,12

Front 277

3-linoleic acid C formula

Back 277

18:3 delta 9, 12, 15

Front 278

Linoleic Acid C formula

Back 278

18:2 delta 9,12

Front 279

Linoleic acid(__:_ delta _, _)
1. Desaturated to _________ __:_ delta _,_, __
2. Elongation (at ___ end) to (__:_ delta _,__, __)
3. Desaturation to ___________ ___ (__:_ delta _, _,__, __)

Back 279

18:2, 9, 12

Linoleoyl 18, 3, 6, 9, 12

COO, 20, 3, 8, 11, 14

Arachnoidyl CoA 20, 4, 5, 8, 11, 14

Front 280

___________ acidis used for synthesisof eicosanoids: prostaglandins

Back 280

Aarachnoidic

Front 281

Arachidonic acidis used for synthesisof ___________: prostaglandins

Back 281

eicosanoids

Front 282

________ ____ elongation& desaturation makes EPA (20:5 D 5, 8,11,14,17)

Back 282

Linoleic Acid

Front 283

Linolenic acid elongation& desaturation
EPA (__:_ delta _, _,__, __,__)

Back 283

20, 5, 5, 8, 11, 14, 17

Front 284

EPA AKA

Back 284

Eicosanoidic Acid

Front 285

Eico: __ carbons
Pentanoic: _ double bonds

Back 285

20

5

Front 286

Where are TAG and VLDL synthesized (2)

Back 286

Liver smooth ER

Adipose

Front 287

Liver uses what substrates to make TAG and VLDL?
Adipose?

Back 287

DHAP, Glycerol

Glycerol only!

Front 288

Intermediate in synthesis of VLDL and TAG

Back 288

Phosphatidic Acid

Front 289

Source of glycerol phosphate in the liver for VLDL adn TAG Syntehseis?

Back 289

DHAP

Glycerol kinase

Front 290

Source of glycerol phosphate in teh adipose for VLDL adn TAG synthesis?

This occurs along with what process?

Back 290

DHAP

Glycolysis

Front 291

G3P + 2FA --> ?

What process is this used in?

Back 291

Phosphatidic acid

VLDL or TAG synthesis

Front 292

G3P + 2FA = Phosphatidic Acid

Where do the FA's com from?

Back 292

Fatty Acyl CoA

Front 293

Phosphatidic acid with phosphate removed

Back 293

Diacylglycerol

Front 294

Diacylglycerol AKA

Back 294

AG

D

Front 295

DAG + FA = ?

Back 295

TAG

Front 296

DAG + FA = TAG
Where does FA come from?

Back 296

FA-CoA

Front 297

Microsomal Transfer Protein AKA

Back 297

MTP

Front 298

Where is MTP located?

Back 298

rough ER

Front 299

__________ _______ _______ (___) onrough ERRequiredfor VLDL (and chylomicron) assembly Gives them __________ ___

Back 299

Microsomal Transfer Protein, MTP

Apoprotein B100

Front 300

VLDLprocessed in _____,packaged into _________ ________in the ER
membrane phospholipids surround ___

Back 300

Golgi, secretory vesicles

TAG

Front 301

Which is denser, VLDL or chylomicrons?

Why?

Back 301

VLDL is denser

Chylomicrons have higher % of TAG

Front 302

Which Apoprotein is on VLDL?

Back 302

Apoprotein B100

Front 303

TAG are stored in adipose cells during the fed or fasting state?

What hormone is involved?

Back 303

Fed

Insulin

Front 304

Nascent ____ pick up CII and E

Back 304

VLDLs

Front 305

Nascent VLDLs pick up which Apolipoproteins?

Back 305

CII

E

Front 306

Nascent VLDLs pick up ___ and _From ___ in circulation
Chylomicrons& VLDLDonate __ to tissue
__ activates LPL (basementmembrane of capillaryendothelial cells)
VLDL --> ___
Chylomicrons-->________
Glycerol-->_____

Back 306

CII, E, HDL

FA

CII

IDL

Remnants

Liver

Front 307

Glucose taken up into adipose cells during fed state.

What happens to it?

Back 307

Undergoes glycolysis.

Converted to DHAP.

DHAP used as substrate for TAG synthesis

Front 308

Adipose LPL isozyme has a ____ Km
Worksbest when chylomicron, VLDL are ____

Back 308

high

high

Front 309

Decreased insulin increased glucagon --> increased ____
Stimulateslipolysis (__ release)
_______ ______ _ Phosphorylates & activates _______-_________ ______

Back 309

cAMP

FA

Protein Kinase A

Hormone sensitive lipase

Front 310

Decreasedinsulin increased glucagon-->increased cAMP
Stimulateslipolysis (FA release)
Proteinkinase A Phosphorylates & activates Hormone-sensitive lipase
FAenter cells of muscle,Othertissues and is _______to produce energy
Glycerol is sent to _____ complexed with _______

Back 310

oxidized

liver, albumin

Front 311

Synthesisof new ________leads to resynthesis ofTAG
Controlsrate of FA release

Back 311

glycerol

Front 312

Adipose: synthesizes newGlycerolfrom ________, _____ _____, or ________

Back 312

lactate, amino acids, pyruvate

Front 313

PEPCK activity?

Induced by what molecule?

requies 2 cofactors?

Back 313

OAA to PEP

cAMP

ATP, GTP

Front 314

In glycerneogenesis, G3P is converted to _____

Then that is converted to ________-_-_________ and __ are added.

What proportion of free FAs are resyntehsized to TAG and retained in the adipose?

Back 314

DHAP

Glycerol-3-Phosphate, FA

30-40%

Front 315

Glycerophospholipids and sphingophsopholipids are components of what?

Back 315

Cell membrane

Front 316

Glycerophospholipids and sphingophospholipids are defined by what?

Back 316

Backbone

Head group (C3)

Front 317

Adipose stores

Blood lipoproteins

What type of molecule?

Back 317

Triacylglycerol

Front 318

Phosphatidylcholine

Phosphatidylethanolamine

Phosphatidylserine

PIP2

Phosphatdiylglycerol

Cardiolipin

What kind of molecule?

Back 318

Glycerophospholipids

Front 319

Plasmalogens

Platelet activating factor

What type of molecule?

Back 319

Ether Glycerolipids

Front 320

Sphingomylein is what type fo molecule?

Back 320

Sphingophospholipids

Front 321

Cerebrosides

Sulfatides

Globosides

Gangliosides

What type of molecule?

Back 321

Glycolipids

Front 322

Triacylglycerols

Glycerophospholipids

Ether glycerolipids

What type of molecule?

Back 322

Glycerolipids

Front 323

Glycerophospholipids

Sphingophospholipids

What type of molecule?

Back 323

Phospholipids

Front 324

Sphingophospholipids and glycolipids

What type of molecule?

Back 324

Sphingolipids

Front 325

Glycerol

3 FA

What molecule?

Back 325

Triacylglycerol

Front 326

Glycerol.

2 FA

Phosphate group - Head group

What molecule?

Back 326

Glycerophospholipid

Front 327

Glycero-ether

FA

Phosphate - Head group

What molecule?

Back 327

Ether glycerolipid

Front 328

Sphingosine

FA

Phosphate - Head Group

What molecule?

Back 328

Sphingophospholipid

Front 329

Sphingosine

FA

Carbohydrate

Whtat molecule?

Back 329

Glycolipid

Front 330

Head groups are hydro______: charged or polar

Back 330

philic

Front 331

Head groups are hydrophilic: ________ or _____

Back 331

charged, polar

Front 332

Phospholipids containing glycerol are synthesized from what intermediate?

Back 332

Phosphatitid acid

Front 333

Phosphatidic Acid --> DAG --> Head group is activated by CDP-->what types of glycerophospholipids?

Back 333

PC

PE

PS

Front 334

Phosphatidic Acid-->DAG-->DAG is activated by CDP--> What types of glycerophospholipids?

Back 334

PI

Cardiolpiin

PG

Front 335

PE& PC __________ areactivated by CDP then added to ___

Back 335

headgroups, DAG

Front 336

PE can be converted to PC
how?

Back 336

3 methylations. Methyl groups donated by SAM

Front 337

PE can be converted to PS
How?

Back 337

Ethanolamine is replaced by serine

Front 338

PS can be converted to PE
How?

Back 338

By decarboxylation

Front 339

___ is activated by CDP to synthesize Cardiolipin andPI

Back 339

DAG

Front 340

DAGis activated by CDP to synthesize ___________ and __

Back 340

cardiolipin, PI

Front 341

•6carbon sugar
'•Attachedat anomeric carbon

Back 341

Inisotol

Front 342

Where is cardiolipin found?

Back 342

inner mitochondrial membrane
heart

Front 343

2 phospatidylglycerolscovalently bound to form what molecule

Back 343

Cardiolipin

Front 344

Premature newborns are Deficient in ____

Back 344

DPPC

Front 345

acute respiratory distresssyndrome

Back 345

ARDS

Front 346

_____: _____________ ratio is Measured to determine lungmaturity

Back 346

DPPC:Sphingomylein

Front 347

At what age do lungs mature in teh womb

WHat happens at this point?

Back 347

DPPC expression, leads to increase in PC and decrease in sphingomylein

Front 348

Major component in lung surfactant

Back 348

DPPC

Front 349

Plasmalogens are synthesized in ___________

Back 349

Peroxisomes

Front 350

Go Over Lecture 3 Slide 33

Back 350

Do it!

Front 351

•Ethanolamineplasmalogen in _____

Back 351

lein

my

Front 352

•Cholineplasmalogen in _____

Back 352

eart

h

Front 353

Platelet Activating Factor AKA

Back 353

PAF

Front 354

PAF is seen in what type of cells?

Back 354

Phagocytic blood cells

Front 355

PAF is similar to which plasmalogen?

Back 355

Choline

Front 356

Difference between PAF and choline?

Back 356

PAF has Acetyl gropu on C2 and Alkyll on C1

Front 357

Glycerophospholipids are broken down by what enzymes?

Where?

Back 357

Phospholipases

Cell membranes or lysosomes

Front 358

C1 is cleaved by which Phospholipase?

Back 358

Phospholipse A1

Front 359

C2 of glycerophospholipid is frequently ______________ ____
Removed to produce _____________

Back 359

arachnadoic acid

eicosanoids

Front 360

Phospholipase that cleaves C2 bond?

Back 360

Phospholipase A2

Front 361

Important in removing oxidizedunsaturated FA groups from glycerophospholipids

Back 361

Phospholipase A2

Front 362

Cleaves phopshate gropu from glycerophospholipid

Back 362

Phospholipase C

Front 363

Cleaves O and head gropu from Glycerophospholipid

Back 363

Phospholipase D

Front 364

Cleaves PIP2to formDAG & IP3 second messengers

Back 364

Phospholipase C

Front 365

Sphingolipids have whaty type of backbone?

Back 365

Ceramidew

Front 366

Function of sphingolipids?

Back 366

Intercellular communication

Front 367

Act as ABO blood group determinants.

What molecule?

Back 367

Sphingolipids

Front 368

Ceramide is syntehsized from wht molecule?

Back 368

Serine

Front 369

Ceramidesynthesis from serine
1._________ ___ condenses with serine (carboxyl group of serine is lost as ___)
2.Reduction to form _________________ (_____)
3. Very long chain fatty acid forms _____bond with _____ group
4. Oxidation to a ______ bond (_____)

Back 369

Palmitoyl CoA, CO2

Dihydrosphingosine, NADPH

amide, amino

double, FADH2

Front 370

Choline is transferred from PC toform the only ___________________: sphingomyelin

Back 370

sphingophospholipid

Front 371

_______ is transferred from __ toform the only sphingophospholipid: ______________

Back 371

Choline, PC, sphingomylein

Front 372

ere is sphingomylein found?

Wh

Back 372

Mylein sheath of nerves

Front 373

Ceramide + Choline = ?

Back 373

Sphinhomylein

Front 374

Ceramide + Galactose = ?

Back 374

Galactocerebroside

Front 375

Ceramide + Gluscose = ?

Back 375

Glucocerebroside

Front 376

Glucocerebroside + NANA = ?

Back 376

Ganglioside

Front 377

Galactocerebroside + Sulfated Galactose = ?

Back 377

Sulfatide

Front 378

Glucocerebroside + Glucose + Galactose = ?

Back 378

Globoside

Front 379

____ donates sulfate to form Sulfatides

Back 379

PAPS

Front 380

___ activates sugars
CDP activates ___, _______________ , & _______

Back 380

UDP

DAG, Ethanolamine, Choline

Front 381

PAPS AKA

Back 381

Active Sulfate

Front 382

Leptin results in what?

Back 382

Weight loss

Front 383

Leptin:results in weight loss
– Released from __________ when TAG levelsare ____
– Binds to receptors in __________
– Signals through ___-____ pathway
– Stimulates release of ____________ _____________
– _____ patients may be leptin resistant

Back 383

adipocytes, high

hypothalamus

Jak-STAT

anorexigenic neuropeptides

Obese

Front 384

Adiponectin
–Secretion _______ as _________ gets larger
–Maybe linked to _______ resistance in obesity
–Receptorssignal activation of ___ activated protein kinase (____)–&transcription of peroxisome proliferator activated receptor a (_____)
–IncreasedFA uptake & oxidation by ______ & _____
–Low adiponection-->more circulating ___
–Antidiabeticdrugs (fibrates& thiazolidinedione)target _____

Back 384

decreases, adipocyte

insulin

AMP, AMPK, PPARa

liver, muscle

fat

PPARa

Front 385

FIbrates

Thiazolidinedione

What type of drugs?

Back 385

Antidiabetic drugs