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Molecules and Cells (Unit 1) > Lipids > Flashcards

Flashcards in Lipids Deck (74):
1

What lipid components have Surfactant, emulsifier/detergent properties?

PL, Bile Acids

2

Treatment strategies for hypercholesterolemia:

1.Drugs that promote bile salt excretion (_________)

2.HMG CoA inhibitors ( _____________)

cholestyramine

statin drugs

3

Fabry’s disease. Deficiency in what enzyme?

α-galactosidase A

4

Platelet-activating factor

•Acetyl group at #______ position

•Mediates platelet aggregation during _______________

2

hemostasis

5

Stearoyl CoA Desaturase

1.Places one ___________ between carbons ________& _________

2.Present in____________

3.Contains three proteins … ______________, __________, and ___________

4.Catalyzes:  stearate  ----->__________

                     palmitate ---->____________

 

1.Increase in dietary polyunsaturated FA ----->  __________in activity

2.Insulin,triiodothyronine, hydrocortisone, cholesterol----->________

  of enzyme

double bond; 9 ; 10

ER

desaturase, cytochrome b5, NADPH-cytochrome b5 reductase

oleic; palmitoleic

decrease

induction

6

Bile salts contribute to lipid___________ via mixed micelle formation

solubilization

7

Regulation of Cholesterol Synthesis and Uptake by Extracellular Cholesterol

1. LDL binds to ______________

2. The membrane-bound LDL is ______________..... by ________ coated vesicles

Vesicles lose clathrin...become ______________

Endosomes...fuse with ___________

                  

LDL receptor ...separates from fused endosome-lysosome vesicles.... returns to _____________

 

membrane receptor

endocytosed; clathrin

endosomes

lyzosomes

cell surface

8

Plasma Lipoproteins

1. Chylomicrons-----Primarily transports---- dietary lipid form  

           ___________ to ___________

2. VLDL--- Primarily transports-----___________from +_______ to ____________ and   other tissues 

3. IDL------Primarily transports--------__________to _________ via conversion   to ___________

4. LDL-----Primarily transports------- __________to____________ 

5. HDL------Primarily transports------- ____________ from ___________to ____________

intestines; adipose.

TAG; liver; adipose

cholesterol; tissues; LDL

cholesterol; tissues

cholesterol;tissues

liver

9

Malic enzyme::   ____________-linked malic enzyme or

  Malate:NADP oxidoreductase _____________

NADP; decarboxylating

10

Can’t process chylomicrons after a fatty meal, then Fat deposits in __________

Skin

11

MCAD Deficiency

The clinical symptoms:____________, __________, and __________

The biochemical symptoms:_______________ and ___________

     

symptoms dependency ~ fatty acid oxidation for energy

 

associated with ___________syndrome/sudden infant death

treatment avoid prolonged periods of______________

    vomiting, lethargy, coma

hypoketotic hypoglycemia,  dicarboxylic aciduria

reyes

starvation

12

Two types of Bile Salts

Primary Bile Acids:    Made in ____________

                                      -contain 2 or 3 _________

Secondary Bile Acids: Derived from _____________

                                  -made in ____________ by micro-organisms.

                                   -contains 1 or 2 ___________

Liver

hydroxyls

primary Acids.

intestine

Hydroxyls.

 

13

Cholesterol

Lo solubility in _________

Precursor to ___________ and ___________

Components of  cell membranes

 

H2O

bile salts & steroid hormones

14

Tay-Sachs disease. Deficiency in what enzyme?

β-Hexosaminidase A

15

Effect of Diet on Chol  synthesis

1.  When dietary cholesterol decreases, Biosynthesis in liver & intestine ____________

2. When dietary cholesterol increases,  Biosynthesis in liver & intestine ________

Note: Cholesterol biosynthesis in the liver and intestine ==> meet the needs of other tissues and organs.

Increases

 Decreases

16

Role of Ketone Bodies

1.Normally ketone body concentration is___________

2..During starvation,---> __________ FA degradation ---->  increased___________---> increased _____________formation---->:energy source for ___________tissue (skeletal & cardiac muscle) + (brain)

3.____________ sparring effect + ___________sparing effect in muscle

4.During prolonged starvation… energy source for _____________

low

increased

Acteyl CoA

ketone body

non-hepatic

Glucose ;protein

nerve tissue

17

Pancreatic lipase reaction occurs at the lipid-water interface of emulsion

droplets and/or mixed micelles.  Pancreatic lipase/colipase produces____________ and _________

FA & 2-monoacylglycerol 

18

1st bile salts. are _________________prior to reabsorption

deconjugated

19

Glycerol released as a result of ____________ hydrolysis is taken up by__________.

TAG;  liver…

20

POLY  UNSATUTATED  FATTY ACID  FUNCTIONS

1.  Maintain  proper membrane fluidity

2.  Precursors to prostaglandins ,  thromboxanes , and Leukotrienes

21

Peroxisomal Oxidation of Fatty Acids

Peroxisomes contain ________________needed for β-oxidation of fatty acids.

Initial dehydrogenase reaction is different.

Peroxisomal β-oxidation is usually more specific for ___________length fatty acids

Peroxisomal β-oxidation will not proceed beyond ________

Therefore peroxisomal products may be oxidized to__________ in _________

enzymes

longer chain

C8

acetyl CoA; mitochondria

22

LpL and Obesity

1.  During fasting/diabetes- ___________ in  fat storage and __________LpL

2.  well fed- _________ fat storage and__________  LpL

3. _______ LpL  in obese patients with enlarged fat cells

4.  __________LpL during the development of obesity

Decrease; decrease

 Increase; increase

 Increase

Increase

 

23

dicarboxylic aciduria

alter. ox  FA

24

FA synthase consists of several different enzyme functions on a single

___________enzyme

multifunctional

25

Tissues Most Active in TAG Synthesis

Tissue: Liver

Source of FA:    __________ and __________ biosynthesis

Utilization:        _______________

___________________________________________________________

Tissue: Adipose

Source of FA:   ____________ and ___________ biosynthesis

Utilization:        ____________

________________________________________________________

Tissue: Intestinal Mucousa

Source of FA:   ___________

Utilization:        ___________

adipose tissue & liver

lipoprotein production

diet & liver

storage

diet

chylomicron synthesis

26

Nieman-Pick. What enyzme is deficient?

sphingomyelinase

27

Cholesterol Synthesis

1. a. liver ==> __________/ ______________

    b. Intestine ==> ___________

    c. Adrenal cortex ==> ______________

    d. reproductive tissues=> ___________

                                          

   reproductive steroids

2. All carbons are from ____________

3. NADPH derived from _____________

4. Synthesized in the __________

bile salts ; lipoproteins

lipoproteins
adrenal steroids

 Reproductive organs

Acetyl CoA

 hexamethylene succinimide

cytosol

28

Lipid membrane components

Sphingolipids, phospholipids, cholesterol

29

COX-1 is _____________

 

COX-1 is most inhibited by ___________

COX-2

______________…and is generated in response to _____________

COX-2

induction is inhibited by ____________

Constitutive …

NSAIDs

Inducible

inflammation

glucocortiods

30

hypoketotic hypoglycemia

can’t deg. FA

31

Sphingolipid  Degradation

1. Overall pathway ...... composed of series of ____________:

2. All reactions .......occur in __________

3. The pathway is the sequential, stepwise   removal of constituents (i.e.) sugars, by ___________

hydrolases

lysosomes
hydrolases.

32

Hormone Sensitive Lipase:  Inhibior: __________     

                                                Activators: _____________,____________, and ______________   

 

LIPOPROTEINLIPASE:  Activator: ___________

Insulin   

Glucagon;  epinephrine; ACTH       

Insulin        ( + )

33

•Two enzymes involved in fatty acid synthesis

 

    a. Acetyl CoA Carboxylase

    b. FA synthase

34

Regulation of Cholesterol Synthesis and Uptake by Extracellular Cholesterol Cont’d

Free chol leaves lyzosomes enters __________ 

In the cytosol increased free cholesterol :

         inhibits_____________

         suppresses ____________

         activates ____________

Down regulation of _____________prevents further uptake and intra-cellular accumulation of cholesterol

cytosol  

HMGCoA Reductase

HMGCoA Reductase

ACAT

Hypercholesterolemia

35

Some LDL & chlylomicron remnants are scavenged by the ____________ system.

macrophage

36

Lipid Transport

1.   Chylomicrons --- Transport ____________ lipid to ___________

2.   Lipoproteins ----- Transport lipid between __________ and __________

3.   Albumin --------- Transport _________from _______ to__________

4.   ketone Bodies -- Transported in solution in__________ (i.e. from liver to skeletal + cardiac tissues)

dietary;adipose

liver; other tissues.

Fatty Acids;adipose;  liver

plasma.

37

Gaucher’s disease. What enyzme is deficient?

β-glucosidase

38

Prostaglandins

1. Synthesized from ______________FA.....20 carbons

                                

2. Three (3) major classes:...... _________, _________, and ________

                            

3. Each class divided in 3 major series:..... 1, 2, 3

                 

                                             

                              

                                  

polyunsaturated

A, E, F

39

PL Synthesis

De novo

    1. Synthesize ___________

   2. Synthesize activated ______________headgroup

   3. Reaction of __________ with __________________--> PL

From pre-existing PLs

       1. Base   Modification reactions

       2. Base   Exchange reactions

    i.e. the identity of PL is established by  identity of _________(polar head group)

Diacylglycerides

Polar

DAG; activated polar head group 
base

 

40

B- Oxidation

Produces: _____________, _________, and ________

FA used as ___________

Occurs in _____________

NADH, FADH2 and Acetyl CoA

FA CoA

mitochondria

41

_____________ + products of _____________lipase/colipase combine to form mixed micelles

Bile salts; pancreatic

42

 Acetyl CoA Carboxylase

1.Allosteric Regulation:  Activator: __________

                                        Inhibitor: ____________

2.Hormonal Regulation: __________ via cAMP ----->   Phosphorylation (________active)

3.  Insulin-----> ___________  (_________active)

4.  Dietary Regulation:   

•___________ carbohydrates /________FAT       ( ____________ enzyme levels)… need to _________ fat

•__________FAT/fasting        (________enzyme levels) … need to ___________ fat

Citrate ;  Palmitate

Glucagon; less

Dephosphorylation; more

High; more;increased; make

High; decreased; degrade

43

Regulation of HMGCoA Reductase

1.   Feedback inhibited by _____________

           (synthesis also repressed by  cholesterol)

2.  Insulin Stimulates  ====>     _____________enzyme

3.   Glucagon  Inhibits  =====>   ______________ enzyme

4.   ______________hormone stimulates  via   induced enzyme synthesis

cholesterol

dephosphorylated

phosphorylated

Thyroid

44

Fatty Acid Synthase

1.   Requires a ___________ molecule. Which is often?

    

2.  Adds __________ carbons at a time via ___________

3.   Requires 2 ___________ for each two carbons added

primer; ( Acetyl CoA )

two ; malonyl CoA

NADPHs

   

45

Activation of HSL

1. Glucagon, epinephrine, or ACTH binds to Membrane Receptor

2. Activates Adenyl cyclase

3. cAMP increases

4. Activates Protein Kinases

5. Phosphorylates “activates” HSL-

6. Insulin inhibits HSL activity via dephos.

46

The COX Story 

Inhibition of COX is needed to provide relief to .____________, ___________ & _________

•Inhibition achieved via _____________

COX-1

Constitutive …. Housekeeping enzyme expressed  in ____________, _________, and __________

COX-1

Mediate the production of _____________ and _____________

 keep integrity of the gastric mucosa, …platelet function, ….renal blood flow

 

Traditional (pre-COX-2) NSAIDs inhibit both COX-1 and COX-2

leads to_________________and potentially ____________ problems

COX-2 inhibitors ….

________________

____________

____________

.pain, inflammations, fever

NSAIDs

gastrointestinal tract, kidneys, and platelets

TXB A2; prostaglandins

gastrointestinal ; kidney

celecoxib (Celebrex)

rofecoxib (Vioxx)

meloxicam (Mobic)

 

47

How are lipids stored>

Triacylglycerides, adipose tissue

48

TAG Synthesis: Key Points

Tag Synthesis Requires:

1.   Fatty_____________CoAs

2.   Glycerol -3 - PO4  (_________and ________)                 

        Dihydroxyacetone - PO4 (_________and ________)                      

         glycerol (in ________ only)

�  In liver and adipose involves __________  and  _________ as intermediates.

�     Intestinal mucousa only _________ + ___________ are intermediates

Acyl

Liver; adipose

Liver; adipose

Liver

phosphatidate ; DAG

DAG

MAG

49

Hormone Sensitive Lipase: release FA from ___________ for energy

LipoProtein Lipase: release FA from lipoproteins for ___________ in _____________& use

in other tissues

adipose

storage; adipose

50

Abeta-lipoproteinemia

Defective synthesis of ______________…

Formation of ____________ and ______________are affected…

Can’t transport _____________lipid for storage

Chylomicrons, VLDLs, and LDLs are absent from _________

Can led to _____________ and ___________.

B apoproteins

chylomicrons & VLDLs

dietary

plasma

Neuropathy and red cell deformations

51

Plasmologens

Ether linkage in #_____ position

Present in __________ & ____________

1

myelin; heart tissue

52

Chemical Properties
of
FATTY ACIDS

1.  Little Attraction for Water

2.   Significant attraction for fatty alkyl   chains

3.   Chemically Inert (generally)

53

Key Points of Dietary Lipid Absorption

I.In the Gastric Lumen:

via the action of ___________and gastric lipases…

  1. Dietary TAG ---------->  Partially emulsified TAG (_________hydrolysis or emulsified)

via __________action of emulsification products, PLs, churning, peristaltic motions…

 2. Partially emulsified TAG ------------> Emulsified TAG

II. In the Intestinal Lumen:

via pancreatic lipase/colipase action…

2. Emulsified TAG ----------> __________+_________

3. FA + MAG + bile salts ---> ____________

III.   At the Intestinal Cell Membrane:

     1.  FA + MAG (from mixed micelles )          diffuse into __________cell.

  IV. Inside Mucosal Cells

        1.   FA + MAG ---------------> ___________

        2.   TAG  ------------------->____________

        3.   Chylomicrons secreted via the      ____________ system.

lingual ; gastric

30%

detergent

FA + MAG

Mixed Micelles

mucosal

TAG

Chylomicrons

  lymphatic

54

Bile Salt Metabolism: Key Pts.

1.   Use in ___________ of dietary fat.

2..  major end products of ______________degradation

3.   Primary bile salts synthesized in___________

4.   Bile salts are re-used

5.  2nd bile salts are made in the ____________ from 1st bile salts

                          

 

             

                            

                              

emulsification

cholesterol 

liver

intestines

55

Triacylglycerols

1.   Stored Energy

2.   Fatty Acid Components are generally __________

3.   Efficient Energy Storage

4.   TAG yield ___________as much ATP as   glycogen

5.   Energy Stored as _________ may last for up to   24 h of fasting

6.   Energy stored as ________may last for as much as   several weeks of fasting  

Reduced

2.5

glycogen

TAG

56

In order to use TAGs for Energy:

F.A. components must be________or _____________

F.A. release involves two lipases:

       A. Hormone - _______________

       B. ___________ Lipase

mobilized

sensitive lipase

Lipoprotein

57

Lipid  pool

(FA, PL,

TAG, SL, lipids in transport

(lipoproteins/chylomicrons)

… chol., chol.-esters, TAG, PL

 

58

Lipid Functions

1.    Energy Storage

2.    Membrane Components

3.    Surface Active Properties

4.    Specific Biological Properties

59

Sphingolipidoses

 

1.  when ____________ enzyme is missing or         defective....

       a.  it’s substrate accumulates in the ______________ of cells

2.  sphingolipidoses......

       b.  the continued ____________ SL  degradation products

 

degradative

lysosomes

accumulation

60

Where does fatty acid synthesis occur?

Cystol

61

atherosclerosis

      a.   occurs over time .... complex   process

      b.   may lead to ____________of   blood flow

   .....___________ infarction / stroke

2.   Two Types

       a.   __________ hypercholesterolemia

       b.   _____________ hypercholesterolemia

restriction

myocardial

dietary

genetic or familial

62

Activation of Lipoprotein Lipase (LpL)

1.   ______________is on surface of lipoproteins

2.   LpL is on ______________ cell surfaces (adipose, cardiac & skeletal muscle)

Therefore, when lipoproteins gets close to cell surface,

                       1.___________

                        2. Cause? __________________

Apo C-II

capillary endothelial

Apo CII associates with LpL

Causing it to become active

63

Hydroxylation

1. Occurs in ___________(many tissues).....

                            .....uses___________F.A.

2.. Nerve Tissue.....

                      ......Uses ___________F.A.

3. F.A. Hydroxylated at # __________ position.

Mitochondria 

short chain

long chain

2

64

Regulation of  β-Oxidation

1. CAT I. Inhibitor: ____________                           

2. beta - Hydroxy CoA DH. Inhibitor: ___________ 

3. Thiolase. Inhibitor: ____________

 Malonyl CoA

 

NADH

Acetyl CoA

65

Reverse Transport of Cholesterol. Definition

The movement of cholesterol from the tissue cells to the liver for elimination…

66

Components of Complex Lipid Synthesis                                                 

 

Phosphatidylglycerol , Leukotrienes, Bile salts, Steroid hormones

67

During fatty acid oxidation the flux of acetyl CoA is such that  Pyruvate DeHydrogenase is ___________& Pyruvate Carboxylase is ___________

During fatty acid synthesis the flux of acetyl CoA is derived from ____________oxidation.

The lowered flux level of ____________ derived from carbohydrate oxidation allows

both __________and ___________ to be active ….

inhibited; activated.

carbohydrate

acetyl CoA

PyrDH;PyrCO2lase

68

Krabbe’s disease

Deficiency in what enzyme?

β-galactosidase

69

VLDLs & HDL are synthesized in____________and Chylomicrons are synthesized in the ___________. Others lipoproteins primarily formed in the ___________. 

liver ; intestine; circulation

70

B- Oxidation Steps

 

                             1. dehydrogenation

            2. hydration

                             3. Oxidation

      4. Cleavage (thiolysis)

71

Synthesis of Fatty Acids  From Palmitate

1. ___________ of the C16 Chain

2. _____________of the C16 Chain

3. ____________of the C16 Chain

4. _____________ and ______________ of the C16 chain

5. _______________, ___________, and ___________ of the   C16 chain

Elongation

Desaturation 

Hydroxylation 

Elongation and Desaturation

72

B- Oxidation

1.__________does not cross inner mitochondrial membrane

2.CAT & CoA on both sides

3.Carnitine acyl carrier

  in inner membrane

  transports C12 ~C18 FA

4. 

  via ______________________

FA

carnitine independent mechanism

73

Inside the liver cholesterol is released from ___________ and is either eliminated directly as cholesterol or converted to_____________ and eventually eliminated as bile salts and/or bile salt metabolic products…

HDL;  bile salts

74

______________is product

  (C16 to C18)

 

 Stearoyl CoA