Ch. 16: Lipids I: FAs & Eicosanoids Flashcards Preview

Medical Biochemistry > Ch. 16: Lipids I: FAs & Eicosanoids > Flashcards

Flashcards in Ch. 16: Lipids I: FAs & Eicosanoids Deck (88):
1

How do you define lipids based on their solubility?

Soluble in non-polar solvents

Not very soluble in water

2

Which lipids are polar?

FAs
Cholesterol
Glycerophosphatides
Glycosphingolipids

3

Which lipids are non-polar?

Triacylglycerols
Cholesterol esters

4

Important functions of lipids?

Thermal insulation (most impt)
Energy storage as TG

5

Difference bet saturated & unsaturated fats?

Saturated: No C=C

Unsaturated: C=C

6

Saturated FAs: Lauric acid

Molecular formula?

C12 H24 O2

7

Saturated FAs: Myristic acid

Molecular formula?

C14 H28 O2

8

Saturated FAs: Palmitic acid

Molecular formula?

C16 H32 O2

9

Saturated FAs: Stearic acid

Molecular formula?

C18 H36 O2

10

Saturated FAs: Arachidic acid

Molecular formula?

C20 H40 O2

11

FA Oxidation: how many net ATP made from 16C fat?

129 net ATP

12

Hormones that bind to receptors to metabolize TAG ➡️ DAG + FA?

3 enzymes involved?

Epinephrine, glucagon

1) adenylate cyclase
2) protein kinase
3) hormone-sensitive lipase

13

⬆️ FA oxidation indicative of what?

What is ⬆️ produced in liver? Made from what?

Starvation
DM

Ketone bodies
Acetyl CoA

14

Name 3 acyl-CoA synthases & what FAs they act on.

Acetyl-CoA synthase: acetate & low wt carboxylic acids

Medium-chain acyl-CoA synthase: FAs w/4-11 C

Acyl-CoA synthase: FAs w/6-20 C

15

How many ATP needed to activate FAs?

2 ATP used (➡️ 131-2 = 129 net ATP)

16

Activation step: FA + CoASH ➡️ acyl-CoA (thioester), using 2 ATP

Location? Enzyme involved?

On outer mitochondrial membrane

Acyl-CoA synthetase

17

Carnitine is synthesized from which a.a.?

Lys & Met

18

Transport of acyl-CoA ➡️ mitochondrial matrix:

1) Acyl-CoA + carnitine ➡️ ?
Enzyme?
Location of rxn?

Acylcarnitine + CoASH

Carnitine palmitoyl-transferase I (CPT I)
Intermembrane space

19

Transport of acyl-CoA ➡️ mitochondrial matrix:

2) Acylcarnitine ➡️ moved into mitochondrial matrix
Enzyme?

Carnitine-acylcarnitine translocase

20

Transport of acyl-CoA ➡️ mitochondrial matrix:

3) Acylcarnitine + CoASH ➡️ ?
Enzyme?
Location?

Acyl-CoA + carnitine

Carnitine-palmitoyl transferase II (CPT II)
mitochondrial matrix

21

What is an allosteric ➖ of CPTI in liver?

Fxn?

Malonyl CoA (Precursor for FA synthesis)

Prevents simultaneous FA oxidation & sythesis

22

What generally occurs in beta-oxidation?

1 run through cycle makes how much ATP?

Oxidation of acyl-CoA at beta C ➡️ 2 Cs removed as acetyl CoA

17 ATP

23

Beta oxidation: step 1?

Enzyme?

Acyl-CoA ➡️ alpha,beta-unsat. acyl-CoA / delta^2-unsat. acyl-CoA + FADH2

Acyl-CoA dehydrogenase

24

Beta oxidation: step 2?

Enzyme?

Alpha,beta- or delta^2-unsat. acyl-CoA ➡️ L-beta-hydroxyacyl-CoA

Enoyl-CoA hydratase

25

Beta oxidation: step 3?

Enzyme?

L-beta-hydroxyacyl-CoA ➡️ beta-ketoacyl-CoA + NADH

L-beta-hydroxyacyl-CoA dehydrogenase

26

Beta oxidation: step 4?

Enzyme?

Beta-ketoacyl-CoA ➡️ acyl-CoA + acetyl-CoA

3-ketoacyl-CoA thiolase

27

What can be done with the acetyl CoA produced from beta-oxidation?

1) TCA cycle
2) cholesterol synthesis (in cytosol)
3) form ketone bodies (liver)

28

Beta-oxidation energetics: palmitate

How are 129 ATP obtained? (Breakdown)

7 FADH2 x 2 = 14 ATP
7 NADH x 3 = 21 ATP
8 acetyl CoA x 12 = 96 ATP
- 2 ATP (FA activation)

29

Regulation of FA oxidation:

Lipogenesis: ➕ and ➖ of acetyl-CoA carboxylase? (➖ and ➕ of FA oxidation)

➕ (➖ FA oxidation): insulin

➖ (➕ FA oxidation): Acyl-CoA, glucagon

30

How are VLCFAs (20 C or longer) oxidized?

1) initial beta-oxidation in peroxisomes (no ATP yield)
2) shortened FAs (LCFAs) ➡️ mitochondria for further oxidation

31

What happens to the FADH2 produced in peroxisomal FA oxidation?

oxidized by O2 ➡️ H2O2 by catalase

32

3 disorders in peroxisomal FA oxidation? What occurs?

Zellweger's syndrome (formation of peroxisomes)
Neonatal adrenoleukodystrophy (⬇️ breakdown of VLCFAs)
Childhood adrenoleukodystrophy (same as #2)

Accumulation of VLCFAs in liver & CNS ➡️ severe neuro problems, death

33

What are sources of propionyl CoA?

Odd number FA oxidation

Catabolism of Ile, Val, Met, Thr

Oxidation of side chain of cholesterol

34

Oxidation of propionyl-CoA ➡️ ? ➡️ ? or ?

Reactions require what vitamins?

Succinyl-CoA ➡️ oxidized or converted to glucose

Biotin
Vit B12

35

What generally occurs in alpha-oxidation of FAs?

Oxidation of LCFA ➡️ 2-OH FA ➡️ oxidation to FA w/one less C

36

Alpha-oxidation disorders: Refsum's disease?

Resulting conditions?

Deficiency of phytanoyl-CoA hydroxylase ➡️ accumulation of phytanic acid

Retinitis pigmentosa, failing night vision, peripheral neuropathy, cerebellar ataxia

37

What generally occurs in omega-oxidation of FAs?

Catalyzed by a monooxygenase that requires ?

Oxidation of C atom most remote from carboxyl group in FA

NADPH, O2, P-450

38

What are the products of omega oxidation of FAs?

Dicarboxylic acids ➡️ further oxidized from either end

39

How does oxidation of mono- & poly-unsaturated FAs differ?

Skips FAD+ step (since double bond already present)

40

General steps of ketone metabolism?

2 acetyl CoA ➡️ acetoacetyl CoA (+ acetyl CoA in) ➡️ HMG CoA ➡️ acetoacetate (+ acetyl CoA out) ➡️ acetone or 3-hydroxybutyrate

41

3 ketones generated in the body?

Acetoacetate
Acetone
3-hydroxybutyrate

42

Where does ketogenesis take place? Cholesterol synthesis?

Ketogenesis: mitochondria

Cholesterol synthesis: cytosol

43

How are ketone bodies generated in liver used by extra hepatic tissues?

1) 3-hydroxybutyrate ➡️ acetoacetate
2) Acetoacetate + succinyl CoA (TCA) ➡️ acetoacetyl CoA + succinate (TCA) (via thiophorase)
3) Acetoacetyl CoA ➡️ 2 acetyl CoA ➡️ TCA cycle

44

Regulation of ketogenesis: 1st point?

Lipolysis (TAG ➡️ FFA in adipocytes)

➕: glucagon, epi

45

Regulation of ketogenesis: 2nd point?

Transport of acyl CoA into MT matrix: Carnitine-palmitoyl transferase I (CPT-I)

➖: ⬆️ malonyl CoA

46

Regulation of ketogenesis: 3rd point?

Acetyl CoA ➡️ ketogenesis or TCA?

Starvation: shunts acetyl CoA to ketogenesis (➖ TCA since oxaloacetate ➡️ PEP in gluconeogenesis)

47

What are long chain fatty acids synthesized from?

Dietary glucose (via pyruvate)

48

Where are the enzymes for fatty acid synthesis located in cell?

Cytosol (different enzymes from FA breakdown)

49

What is required for FA synthesis?

Reduced NADPH (from HMP shunt)
ATP

50

What is initial & control step in FA synthesis?

Enzyme? Requires what co-factor?

Acetyl CoA ➡️ Malonyl CoA
(CO2 transfered from HCO3- ➡️ enzyme ➡️ acetyl CoA)

Acetyl CoA carboxylase (requires biotin)

51

What are the 8 proteins (7 enzymes + carrier protein) that make up the FA synthase multi-enzyme complex?

Ketoacyl synthase
Acetyl transacylase
Malonyl transacylase
Hydratase
Enoyl reductase
Ketoacyl reductase
Acyl carrier protein (ACP)
Thioesterase

52

FA synthase multi-enzyme complex: What vitamin does the acyl carrier protein (ACP) need?

What important residue does it contain?

Pantothenic acid (4'-P-panthotheine)

Contains SH residue (ketoacyl synthase also contains SH from Cys)

53

Where does the first acetyl group come from (to start FA synthesis)?

What provides subsequent acetyl groups?

Acetyl CoA ("seed")

Malonyl CoA

Ex: C15 & C16 of palmitate is from acetyl CoA ➡️ C1-C14 from Malonyl CoA

54

What are the first 5 reactions (in order) of FA synthesis? Enzymes for each step?

1) priming reaction (acetyl transacylase / malonyl transacylase)
2) condensation (beta-ketoacyl synthase)
3) 1st reduction w/NADPH (beta-ketoacyl reductase)
4) dehydration (beta-hydroxyacyl dehydratase)
5) 2nd reduction w/NADPH (enoyl reductase)

55

After first 5 reactions of FA synthesis, what are the 2 possible following steps?

If acyl group is 16 C: enzyme loses affinity, releases palmitate (via thioester hydrolase)

If acyl group is not yet 16 C: acyl group transferred to beta-ketoacyl synthase, return to reaction 1

56

What are the 3 generators of NADPH in the cytosol? (➡️ used in lipogenesis)

1) pentose P pathway
2) isocitrate dehydrogenase
3) malic enzyme

57

How is acetyl CoA used in lipogenesis obtained?

MT: Acetyl CoA + oxaloacetate ➡️ Citrate, moved out of MT ➡️ cytosol (via anti-port w/malate) ➡️ oxaloacetate + acetyl CoA (via ATP citrate lyase)

58

How are FAs with > 16 C (18-24 Cs) made?

Elongation of palmitate in ER or MT (liver)

59

What are the two essentials FAs? (Common name, omega series, systematic name, formula)

Linoleic acid (omega 6; 9,12-octadecadienoic; C18 H32 O2)

Alpha-linolenic acid (omega 3; 9,12,15-octadecatrienoic; C18 H30 O2)

60

What important compounds are derived from the 2 essential FAs?

Linoleic acid ➡️ arachidonic acid

Alpha-linolenic acid ➡️ docosahexaenoic acid (DHA)

61

Almost all naturally occurring, unsaturated LCFAs exist as which isomer?

Cis isomer

62

Unsaturated FAs: Palmitoleic acid

Systematic name? Molecular formula? Omega series?

9-hexadecenoic

C16 H30 O2

Omega 7

63

Unsaturated FAs: Oleic acid

Systematic name? Molecular formula? Omega series?

9-octadecenoic

C18 H34 O2

Omega 9

64

Unsaturated FAs: Arachidonic acid

Systematic name? Molecular formula? Omega series?

5,8,11,14-eicosatetraenoic

C20 H32 O2

Omega 6

65

Main 2 functions of unsaturated FAs?

1) fluidity of TG reserves, phospholipid membranes

2) precursors of eicosanoids

66

What are the 2 most common monounsaturated FAs in mammals?

How are their double bonds introduced?

Palmitoleic acid
Oleic acid

ER: double bond (bet C9-C10) via FA oxygenase (requires O2 & NADPH)

67

Arachidonic acid is precursor for what 4 compounds?

Prostaglandins (via cyclooxygenase)
Thromboxanes
Prostacyclins

Leukotrienes (via 5-lipoxygenase)

68

How are EFAs (precursor FAs) stored?

How are they released?

As esters of 2-position of glycerol backbone of cell membrane phospholipids

Activation of appropriate phospholipase

69

What activates phospholipase A2 ➡️ release arachidonic acid?

Stimuli ➡️ Intracellular Ca2+ w/calmodulin ➡️ activates phospholipase A2 (and C)

70

What inhibits phospholipase A2 activity?

Glucocorticoids (cortisol)

71

Inhibitors of cyclooxygenase?

Aspirin
Indomethacin

Selective for COX2: Celecoxib, Rofecoxib

72

Synthesis of prostanoids: first 3 substrates?

Arachidonic acid ➡️ PGG2 ➡️ PGH2

73

Synthesis of prostanoids: 5 pathways from PGH2

PGH2 ➡️ PGI2 (➡️ 6-keto-PGF-1alpha)

Enzyme?

prostacyclin synthase


74

Synthesis of prostanoids: 5 pathways from PGH2

PGH2 ➡️ PGE2

Enzyme?

PGE2 endoperoxide isomerase

75

Synthesis of prostanoids: 5 pathways from PGH2

PGH2 ➡️ PGD2

Enzyme?

PGD2 endoperoxide isomerase

76

Synthesis of prostanoids: 5 pathways from PGH2

PGH2 ➡️ PGF-2alpha

Enzyme?

PGF-2alpha endoperoxide isomerase

77

Synthesis of prostanoids: 5 pathways from PGH2

PGH2 ➡️ TXA2 (➡️TXB2)

Enzyme?

Thromboxane synthase

78

Eicosanoids: PGD2

Major site of synthesis? Major biological activities?

Mast cells

➖ platelet & leukocyte aggregation
➕ vasodilation, cAMP levels
⬇️ T cell proliferation, lymphocyte migration, IL-1a, IL-2

79

Eicosanoids: PGE2

Major site of synthesis? Major biological activities?

Kidney, spleen, heart

➕vasodilation, cAMP levels
➕ uterine contractions
➕ platelet aggregation
Keeps fetal ductus arteriosus open
⬇️ T cell proliferation, lymphocyte migration, IL-1a, IL-2

80

Eicosanoids: PGF-2 alpha

Major site of synthesis? Major biological activities?

Kidney, spleen, heart

➕ vasoconstriction
➕ bronchoconstriction
➕ smooth muscle contraction

81

Eicosanoids: PGH2

Major biological activities?

➕ platelet & leukocyte aggregation
➕ vasoconstriction

82

Eicosanoids: PGI2

Major site of synthesis? Major biological activities?

Heart, vascular, endothelial cells

➖ platelet aggregation & leukocyte aggregation
➕ vasodilation, cAMP levels
⬇️ T cell proliferation, lymphocyte migration, IL-1a, IL-2

83

Eicosanoids: TXA2

Major site of synthesis? Major biological activities?

Platelets

➕ platelet aggregation
➕ vasoconstriction
➕ lymphocyte proliferation
➕ bronchoconstriction

84

Eicosanoids: TXB2

Major site of synthesis? Major biological activities?

Platelets

➕ vasoconstriction

85

Eicosanoids: LTB4

Major site of synthesis? Major biological activities?

Neutrophils, monocytes, eosinophils, basophils, mast cells, epithelial cells

vascular permeability
➕ leukocyte chemotaxis & aggregation
T cell proliferation, INF-gamma, IL-1, IL-2

86

Eicosanoids: LTC4

Major site of synthesis? Major biological activities?

Monocytes & alveolar macs, Eosinophils, Basophils, Mast cells, Epithelial cells

➕ Microvascular vasoconstrictor
Vascular permeability
➕ Bronchoconstriction
➕ INF-gamma
Part of SRS-A

87

Eicosanoids: LTD4

Major site of synthesis? Major biological activities?

Monocytes & alveolar macs, eosinophils, mast cells, epithelial cells

➕ Microvascular vasoconstrictor
Vascular permeability
➕ Bronchoconstriction
MAIN part of SRS-A
➕ INF-gamma

88

Eicosanoids: LTE4

Major site of synthesis? Major biological activities?

Basophils, mast cells

Microvascular vasoconstrictor
Bronchoconstriction
Part of SRS-A