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Biochemistry > Semester 2: Metabolism of lipids > Flashcards

Semester 2: Metabolism of lipids Flashcards

1
Q

Mobilization of triacylglycerols store in adipose tissue

A
  1. Glucagon, adrenalin, ACTH attaches to receptor
  2. Activates Gs -> adenylyl cyclase -> ATP to cAMP -> PKA
  3. Phosphorylation of Perilipin and HSL (hormone sensitive lipase)
  4. CGI dissociates from Perilipin then associates with ATGL (adipocyte triglyceride lipase)
  5. TG -> DG + FA
  6. HSL: DG -> MG + FA
  7. MGL (monoglycerol lipase): MG -> glycerol + FA
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2
Q

How are fatty acids carried in the bloodstream?

A

Bound to albumin

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3
Q

Activation of fatty acids

A

FA + ATP + CoA Acyl-CoA + PPi + AMP

Takes place in cytosol

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4
Q

Transport of fatty acids into mitochondria: Acyl-Coa synthetase

A
  • In outer mitochondrial membrane

- Catalyzing: Fatty acids -> Fatty acyl-CoA (ATP+CoA -> AMP+PPi)

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5
Q

Transport of fatty acids into mitochondria: Carnitine-acyltransferase I

A
  • Outer mitochondrial membrane
  • Catalyzing: Fatty acyl-CoA + carnitine -> CoA-SH + Acylcarnitine
  • Inhibitor: Malonyl CoA
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6
Q

Transport of fatty acids into mitochondria: Carnitine-acyltransferase II

A
  • Inner mitochondrial membrane
  • Catalyzing: Acylcarnitine into matrix, carnitine to intermem. space
  • CoA-SH + acylcarnitine -> acyl-CoA that can enter beta-ox.
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7
Q

How to convert glycerol to glycolysis intermediate?

A

Glycerol -> glycerol-3-p -> dihydroxyacetone phosphate

enzymes: glycerol kinase, glycerol-p-dehydrogenase

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8
Q

What is PPAR?

A

Peroxisome proliferator/activated receptors - nuclear receptor - transcription factor

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9
Q

PPARalpha

A
  • In muscle, adipose tissue, liver

- Regulates the transcription of fatty acid transporters, CPTI and II + acyl-CoA dehydrogenase

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10
Q

Ketone bodies

A

1) Acetoacetate
2) D-beta-hydroxybutyrate
3) Acetone

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11
Q

When does ketogenesis occur?

A

When there is a high rate of fatty acid oxidation

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12
Q

Lipogenesis, enzyme?

A

Fatty acid synthase - has 7 active sites for different reactions in separate domains

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13
Q

Cofactor requirements for fatty acid synthase

A
  • NADPH
  • ATP
  • Mn2+
  • Biotin
  • HCO3-
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14
Q

Where does beta-ox. occur?

A

Mitochondrial matrix

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15
Q

Where does lipogenesis occur?

A

Cytosol

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16
Q

Committed step in lipogenesis

A

Formation of malonyl-CoA from acetyl-CoA (+bicarbonate)

Via acetyl-CoA carboxylase (prosthetic group: biotin)

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17
Q

Reactions catalyzed by acetyl-CoA carboxylase

A
  1. Transfer of carboxyl group to biotin (ATP-dep.) - Biotin (E1) carboxylase
    - –> Activated CO2 is moved to transcarboxylase active site
  2. Transfer of activated carboxyl group from biotin to acetyl-CoA
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18
Q

Source of NADPH for fatty acid synthesis

A

1) Malate + NADP -> Pyruvate + NADPH+H (by malic enzyme)

2) Glucose-6-p -> Ribulose-5-p (PPP) - Makes two NADPH

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19
Q

Lipids transported from intestines in ….

A

Chylomicrons

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20
Q

Lipids transported from liver in…

A

VLDL

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21
Q

Apolipoprotein of VLDL

A

B-100, Apo Cs

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22
Q

Apolipoprotein of LDL

A

Apo B (B-100)

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23
Q

Apolipoprotein of Chylomicrons

A

Apo As and Cs, E, B-48

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24
Q

HDL is synthesized and secreted in..

A

Both liver and intestine

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25
Q

Function of SRB1

A
  • (Scavenger receptor class B member 1)
  • Is a HDL receptor - accepts cholesterol from HDL
  • HDL3 can accept cholesterol from tissue via this R.
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26
Q

Function of ABCA1

A

Mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins (apo-A1 and apoE), which then form nascent high-density lipoproteins (HDL)

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27
Q

Role of LDL

A

Supply cholesterol and cholesterol esters to many tissues

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28
Q

Role of HDL

A

Removes free cholesterol from tissues and transport it to the liver

29
Q

Cholesteryl ester formation in HDL

A

Phosphatidylcholin (lecithin) + cholesterol –> lysolecithin + cholesteryl ester (by Lecithin-cholesterol acyl transferase (LCAT))

30
Q

Function of StAR

A

Steroidogenic acute regulatory protein is essential for transport of cholesterol to inner mitochondrial membrane

31
Q

Cortisol inactivation done by..

A

11betaOHSDH2 (cofactor: NAD)

32
Q

Cortisol activated by…

A

11betaOHSDH1 (cofactor: NADPH)

33
Q

Cushing syndrome

A

Excess cortisol

34
Q

Adrenal cortex insufficiency

A

Lack of cortisol

35
Q

Side effects of glucocorticosteroids

A
  • Osteoclastogenesis increases –> increased bone resorption
  • Osteoblastogenesis decreases –> decreased bone formation
  • Increased apoptosis of osteocytes –> decreased bone formation
    = osteoporosis
36
Q

Congenital adrenal hyperplasia

A

Defect in cortisol synthesis

- Most frequent: Partial or complete deficiencies of 21hydroxylase, or 11beta hydroxylase

37
Q

From arachidonic acid we will further get:

A

1) Cyclooxygenase pathway –> prostaglandins, thromboxanes

2) Lipoxygenase pathway –> lipoxins, leukotrienes

38
Q

Cyclooxygenase catalyzes what reaction?

A

Arachidonic acid –> PGG2

39
Q

Peroxidase catalyzes what reaction?

A

PGG2 –> PGH2

40
Q

Where can we find TXA2 and what is its function?

A

Platelets, increases calcium –> Platelet aggregation + vascular smooth muscle contraction

41
Q

Where can we find PGI and what is its function?

A

Endothelial cells, cAMP increase –> Platelet aggregation + vascular smooth muscle contraction

42
Q

Where can we find PGD2 and what is its function?

A

Mast cells

  • Increases calcium –> pulmonary vasoconst. + bronchoconstriction
  • Increases cAMP –> vasodilation, relaxation of GI and uterus muscle
43
Q

Prostaglandin F2alpha

A

Inc. Ca2+ –> smooth muscle cell contr. in bronchi, vessel wall, uterus, GI tract

44
Q

Prostaglandin E2

A

Protection of gastric mucosa, bronchodilation etc.

45
Q

COX-1

A
  • Mostly in cytosol
  • Narrow substrate-binding site (completely blocked by aspirin)
  • PG products secreted
46
Q

COX-2

A
  • Mostly in nuclear mem.

- Less inhibition by aspirin than COX1 due to wider substrate binding site

47
Q

What does aspirin do?

A

Inhibits cyclooxygenase enzymes by acetylating Ser. Inactivates COX1, switches catalytic activity of COX2

48
Q

Dioxygenase enzyme

A

Arachidonic acid –> 5-HPETE

49
Q

Dehydrase enzyme

A

5-HPETE –> LTA4

50
Q

LTA4 hydrolase enzyme

A

LTA4 –> LTB4

51
Q

Rate limiting step in fatty acid oxidation

A

Transport of carnitine-acylcarnitine (via CPT1)

52
Q

Acetyl-CoA dehydrogenase

A

Palmitoyl CoA + FAD+ –> Trans-delta2-enoyl-CoA + FADH2

53
Q

Enoyl-CoA hydratase

A

Trans-delta2-enoyl-CoA + H2O–> L-beta-hydroxyacyl-CoA

54
Q

Beta-hydroxyacyl-CoA dehydrogenase

A

L-beta-hydroxyacyl-CoA + NAD+ –> beta-ketoacyl-CoA + NADH+ H

55
Q

Acyl-CoA acetyltransferase (thiolase)

A

Beta-ketoacyl-CoA + CoA-SH –> (C14) Acyl-CoA (myristoyl-CoA) + Acetyl-CoA

56
Q

1 step of ketone body formation: thiolase

A

2 acetyl-CoA —> Acetoacetyl-CoA + CoA-SH

57
Q

HMG-CoA synthase

A

Acetoacetyl-CoA –> HMG-CoA

Acetyl-Coa + H2O -> CoA-SH

58
Q

HMG-CoA lyase

A

HMG-CoA –> Acetoacetate + acetyl-CoA

59
Q

Final reaction in ketone body formation: Acetoacetate to…

A
  • Beta-hydroxybutyrate (beta-hydroxybutyrate dehydrogenase, uses NADH)
  • Acetone (Acetoacetate decarboxylase, releasing CO2)
60
Q

Beta-ketoacyl-CoA transferase

A

Acetoacetate –> Acetoacetyl-CoA

Succinyl-CoA -> succinate

61
Q

Where can we find ACAT2?

A

Enterocytes, hepatocytes

62
Q

Where can we find ACAT1?

A

Kuppfer cells, macrophages

63
Q

HMG-CoA reductase

A

HMG CoA –> Mevalonic acid + CoA

  • (In cholesterol synthesis)
  • Uses 2NADPH+ 2H+
64
Q

How is cholesterol transferred to HDL?

A

1) passive diffusion
2) via SR-BI
3) via ABCA1

65
Q

Coenzymes for bile acid synthesis

A

NADPH, NAD, CoA

66
Q

LXR receptor

A
  • liver x receptor
  • ligand: oxysterol
  • inc. bile acid synthesis
  • inc. cholesterol efflux
  • dec. LDL receptors
67
Q

FXR

A
  • farnesoid x receptor
  • ligand: bile acids
  • inc. bile acid reabsorption
  • inc. LDL receptor
68
Q

SHP

A

Dec. bile acid synthesis

Biochemistry (9 decks)

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