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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
Function of SRB1
- (Scavenger receptor class B member 1) - Is a HDL receptor - accepts cholesterol from HDL - HDL3 can accept cholesterol from tissue via this R.
26
Function of ABCA1
Mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins (apo-A1 and apoE), which then form nascent high-density lipoproteins (HDL)
27
Role of LDL
Supply cholesterol and cholesterol esters to many tissues
28
Role of HDL
Removes free cholesterol from tissues and transport it to the liver
29
Cholesteryl ester formation in HDL
Phosphatidylcholin (lecithin) + cholesterol --> lysolecithin + cholesteryl ester (by Lecithin-cholesterol acyl transferase (LCAT))
30
Function of StAR
Steroidogenic acute regulatory protein is essential for transport of cholesterol to inner mitochondrial membrane
31
Cortisol inactivation done by..
11betaOHSDH2 (cofactor: NAD)
32
Cortisol activated by...
11betaOHSDH1 (cofactor: NADPH)
33
Cushing syndrome
Excess cortisol
34
Adrenal cortex insufficiency
Lack of cortisol
35
Side effects of glucocorticosteroids
- Osteoclastogenesis increases --> increased bone resorption - Osteoblastogenesis decreases --> decreased bone formation - Increased apoptosis of osteocytes --> decreased bone formation = osteoporosis
36
Congenital adrenal hyperplasia
Defect in cortisol synthesis | - Most frequent: Partial or complete deficiencies of 21hydroxylase, or 11beta hydroxylase
37
From arachidonic acid we will further get:
1) Cyclooxygenase pathway --> prostaglandins, thromboxanes | 2) Lipoxygenase pathway --> lipoxins, leukotrienes
38
Cyclooxygenase catalyzes what reaction?
Arachidonic acid --> PGG2
39
Peroxidase catalyzes what reaction?
PGG2 --> PGH2
40
Where can we find TXA2 and what is its function?
Platelets, increases calcium --> Platelet aggregation + vascular smooth muscle contraction
41
Where can we find PGI and what is its function?
Endothelial cells, cAMP increase --> Platelet aggregation + vascular smooth muscle contraction
42
Where can we find PGD2 and what is its function?
Mast cells - Increases calcium --> pulmonary vasoconst. + bronchoconstriction - Increases cAMP --> vasodilation, relaxation of GI and uterus muscle
43
Prostaglandin F2alpha
Inc. Ca2+ --> smooth muscle cell contr. in bronchi, vessel wall, uterus, GI tract
44
Prostaglandin E2
Protection of gastric mucosa, bronchodilation etc.
45
COX-1
- Mostly in cytosol - Narrow substrate-binding site (completely blocked by aspirin) - PG products secreted
46
COX-2
- Mostly in nuclear mem. | - Less inhibition by aspirin than COX1 due to wider substrate binding site
47
What does aspirin do?
Inhibits cyclooxygenase enzymes by acetylating Ser. Inactivates COX1, switches catalytic activity of COX2
48
Dioxygenase enzyme
Arachidonic acid --> 5-HPETE
49
Dehydrase enzyme
5-HPETE --> LTA4
50
LTA4 hydrolase enzyme
LTA4 --> LTB4
51
Rate limiting step in fatty acid oxidation
Transport of carnitine-acylcarnitine (via CPT1)
52
Acetyl-CoA dehydrogenase
Palmitoyl CoA + FAD+ --> Trans-delta2-enoyl-CoA + FADH2
53
Enoyl-CoA hydratase
Trans-delta2-enoyl-CoA + H2O--> L-beta-hydroxyacyl-CoA
54
Beta-hydroxyacyl-CoA dehydrogenase
L-beta-hydroxyacyl-CoA + NAD+ --> beta-ketoacyl-CoA + NADH+ H
55
Acyl-CoA acetyltransferase (thiolase)
Beta-ketoacyl-CoA + CoA-SH --> (C14) Acyl-CoA (myristoyl-CoA) + Acetyl-CoA
56
1 step of ketone body formation: thiolase
2 acetyl-CoA ---> Acetoacetyl-CoA + CoA-SH
57
HMG-CoA synthase
Acetoacetyl-CoA --> HMG-CoA | Acetyl-Coa + H2O -> CoA-SH
58
HMG-CoA lyase
HMG-CoA --> Acetoacetate + acetyl-CoA
59
Final reaction in ketone body formation: Acetoacetate to...
- Beta-hydroxybutyrate (beta-hydroxybutyrate dehydrogenase, uses NADH) - Acetone (Acetoacetate decarboxylase, releasing CO2)
60
Beta-ketoacyl-CoA transferase
Acetoacetate --> Acetoacetyl-CoA | Succinyl-CoA -> succinate
61
Where can we find ACAT2?
Enterocytes, hepatocytes
62
Where can we find ACAT1?
Kuppfer cells, macrophages
63
HMG-CoA reductase
HMG CoA --> Mevalonic acid + CoA - (In cholesterol synthesis) - Uses 2NADPH+ 2H+
64
How is cholesterol transferred to HDL?
1) passive diffusion 2) via SR-BI 3) via ABCA1
65
Coenzymes for bile acid synthesis
NADPH, NAD, CoA
66
LXR receptor
- liver x receptor - ligand: oxysterol - inc. bile acid synthesis - inc. cholesterol efflux - dec. LDL receptors
67
FXR
- farnesoid x receptor - ligand: bile acids - inc. bile acid reabsorption - inc. LDL receptor
68
SHP
Dec. bile acid synthesis

Biochemistry (9 decks)

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