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COB Biochemistry > Lectures 31-32: Lipid Metabolism > Flashcards

Lectures 31-32: Lipid Metabolism Flashcards

1
Q

Which lipases break down short and medium chain fatty acids in triacylglycerols

A

Lingual (tongue) and gastric (stomach) lipase

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2
Q

What emulsifies fats and where does this occur?

A

Bile salts; small intestine

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3
Q

Which lipase digests all lengths of fatty acids? What are the end products of lipase digestion?

A

Pancreatic lipase; Forms 2 fatty acids and 1 monoacylglycerol

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4
Q

Secretin

A

Hormone released in response to acidic material which signals release of bicarbonate to increase pH to 6, a more optimal pH for intestinal enzymes

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5
Q

Esterase

A

Removes fatty acids from cholesterol esters

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6
Q

Phospholipase A2

A

Removes fatty acids from phospholipids

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7
Q

What is the course of small to medium chain fatty acids once in the small intestine?

A

Absorbed by intestinal epithelial cells, enter portal blood and transported to liver bound to serum albumin

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8
Q

What is the course of long chain fatty acids and 2-MAGs once in the small intestine?

A

Packaged into micelles, emulsified by bile salts and absorbed across microvilli

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9
Q

Chylomicrons

A

Package of proteins, phospholipids, cholesterol, fat soluble vitamins and recombined TAGs

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10
Q

What is the major apoprotein involved in the synthesis of chylomicrons?

A

B48

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11
Q

Where does the re-synthesis of TAGs occur and what molecule acts as an activator/primer for this process?

A

Intestinal cells; CoA primes FA to reform TAG and uses apoprotein B48 and other lipids to synthesize chylomicron

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12
Q

Describe the pathway of a nascent chylomicron to the point that it becomes a mature chylomicron

A

Secreted by intestinal cells into the lymphatic system and enter the blood via thoracic duct. Once they accept ApoE or ApoCII from HDL in lymph and blood, they become mature chylomicrons

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13
Q

ApoE

A

Recognized by receptors on the surface of liver cells allowing endocytosis

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14
Q

ApoCII

A

Activates lipoprotein lipase present on capillary endothelial cells in muscle and adipose tissue which digests chylomicrons

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15
Q

Lipoproteinlipase

A

Hydrolyze TAGs and releases fatty acids to adipocytes

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16
Q

What steps are required to utilize fatty acids as fuel?

A
  1. Mobilization: TAGs in adipose tissue broken down into FA and glycerol, released and transported to energy requiring tissue
  2. Activation: Fatty acids must be activated and transported into mitochondria
  3. Degradation: Stepwise breakdown of FA into acetyl CoA and processed in the TCA cycle
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17
Q

Which hormones would stimulate mobilization of Fatty Acids from Adipocytes?

A

Glucagon, epinephrine

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18
Q

What stimulates the phosphorylation/activation of Perilipin and hormonally sensitive lipase?

A

Protein kinase A

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19
Q

What stimulates adipose triglyceride lipase to cleave a FA from the TAG?

A

Perilipin

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20
Q

What hormone would inhibit the action of hormonally sensitive lipase?

A

Insulin

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21
Q

What are the products of lipolysis and what are their destinations?

A

Glycerol: Liver for glycolysis, gluconeogenesis

Fatty acids: oxidation to acetyl CoA for use in TCA

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22
Q

Glycerol kinase

A

Present ONLY in the liver; ustilizes ATP to phosphorylate glycerol in metabolism of glycerol

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23
Q

How is glycerol metabolized?

A

Phosphorylated via glycerol kinase, oxidized via glycerol phosphate dehydrogenase to make DHAP/GAP which can be used in glycolysis, gluconeogenesis, TAG synthesis

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24
Q

Where does fatty acid activation occur?

A

Cytosol

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25
Q

What is the purpose of the carnitine shuttle?

A

Carries long-chain FACoAs across mitochondrial membrane

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26
Q

Where does beta-oxidation occur?

A

Mitochondrial matrix

27
Q

What enzyme is responsible for priming fatty acid oxidation and functions to trap fatty acids in the cell?

A

Acyl-CoA synthetase

28
Q

Acyl Carnitine Translocase

A

Carnitine carries acyl group across membrane and into matrix to make Acyl CoA, and then is flipped back out to the cytoplasm

29
Q

What is the first step of beta oxidation and what is the ATP yield of this reaction?

A

Oxidation

FADH2 produces 1.5 ATP (ETC)

30
Q

What is the second step of beta oxidation?

31
Q

What is the third step of beta oxidation and what is the ATP yield of this reaction?

A

Oxidation

NADH2 produces 2.5 ATP (ETC)

32
Q

What is the 4th step of beta oxidation and what is the ATP yield of this reaction?

A

Thiolysis

Acetyl-CoA produces 10 ATP (TCA)

33
Q

What is the energy yield of Palmitoyl CoA?

A

106 ATP

8 Acetyl CoA, 7FADH2, 7NADH, 7H - 2 ATP used

34
Q

Isomerase (cis-delta3-Enoyl CoA isomerase)

A

Required by unsaturated (double bonds) and odd chain fatty acids for degradation; changes double bond from cis to trans form

35
Q

Reductase (2,4-Dienoyl CoA reductase)

A

Required by odd chain fatty acids for degradation

36
Q

What is the consequence of low oxaloacetate (resulting from a low carbohydrate diet)?

A

Excess acetyl CoA that will condense to form ketone body

37
Q

Identify the 3 types of ketone bodies formed from excess Acetyl CoA

A

Acetoacetate, D-3-Hydroxy-butyrate, Acetone

38
Q

What condition may develop when glucose is not utilized in the liver and free fatty acid forms ketone bodies resulting in a lowered pH?

A

Diabetic Ketoacidosis - may result in coma, death

39
Q

What is the major source of carbon for fatty acid synthesis?

A

Dietary carbohydrates

40
Q

Where does fatty acid synthesis occur?

41
Q

What are the steps of fatty acid synthesis?

A
  1. Formation of Acetyl CoA
  2. Acetyl CoA converted to Malonyl CoA
  3. Elongation (C’s added in pairs)
  4. Desaturation (double bonds)
42
Q

What is the rate-limiting step in fatty acid synthesis and what enzyme is involved?

A

Conversion of Acetyl CoA to Malonyl CoA via carboxylation (Acetyl CoA Carboxylase)

43
Q

How is Acetyl CoA Carboxylase positively regulated?

A

Citrate (allosteric), dephosphorylation, insulin (fed state), high carb/low fat diet

44
Q

How is Acetyl CoA Carboxylase negatively regulated?

A

Long chain FAs (allosteric), phosphorylation, epinehrine (exercise), glucagon (hungry state), high fat/low carb diet

45
Q

Fatty Acid Synthase Complex

A

All reactions of fatty acid synthesis occur here; large multi-enzyme complex with 2 identical monomers; each monomer has 7 catalytic activities and an acyl carrier protein (with PP residue)

46
Q

List the sequence of reactions involved in Fatty Acid Synthesis

A
  1. Condensation
  2. Reduction
  3. Dehydration
  4. Reduction
47
Q

What positively regulates FAS?

A

Presence of phosphorylated sugar (Allosteric)

High carb/low fat diet (Increases FAS synthesis)

48
Q

What negatively regulates FAS?

A

High fat diet, starvation (lowers FAS synthesis)

49
Q

What enzymes are involved in desaturation of fatty acids (introducing double bonds)

A

NADH-cytochrome b5 reductase, Cytochrome b5, Stearoyl CoA desaturase

50
Q

Name the sequence of molecules involved in synthesis of fatty acids before they are released into the blood?

A

Glycerol or glucose, G3P, Phosphaditic acid, Diacylglycerol, Triacylgycerol

51
Q

What is the product of TAGs and apoproteins that is secreted into the blood?

A

Very Low Density Lipoproteins (VLDLs)

52
Q

What is an eicosanoid?

A

Product of fatty acid oxidation; they are signaling molecules that serve as local messengers

53
Q

What are the 4 families of eicosanoids?

A

Prostaglandins, prostacyclins, thromoxanes, leukotrienes

54
Q

What are some metabolic actions of prostaglandins?

A

Promotion of sleep, smooth muscle contraction, inducing pain/heat/fever, bronchoconstriction, uterine contraction, inhibition of platelet aggregation, vasodilation, implantation

55
Q

What are some metabolic actions of thromboxanes?

A

Stimulation of platelet aggregation, vasoconstriction

56
Q

What is a metabolic action of leukotrienes?

A

Leukocyte chemotaxis

57
Q

Describe the process of phospholipid synthesis (Mechanism 1)

A

Phosphatase cleaves a phosphate group producing diacylglycerol which is combined with an activated choline head group to form PC or PE (CMP released)
*In this mechanism, the HEAD GROUP is activated

58
Q

Describe the process of phospholipid synthesis (Mechanism 2)

A

CTP cleaves 2 phosphate groups from phosphatidic acids forming CDP-Diacylglycerol; head group then attaches to produce PI or cardiolipin
*In this mechanism, the DIACYLGLYCEROL is activated

59
Q

What is the rate-limiting step in cholesterol biosynthesis?

A

Conversion of Acetyl-CoA to Mevalonate via HMG CoA Reductase (this enzyme is a target of statins)

60
Q

From what protein does the ring formation begin during cholesterol biosynthesis?

61
Q

Summarize stage I of cholesterol biosynthesis

A

The committed/rate-limiting step: synthesis of mevalonate from Actyl CoA (HMG-CoA Reductase)

62
Q

Summarize stage II of cholesterol biosynthesis

A

Isomerization of dimethylallyl pyrophoshate to squalene utilizing PPi and NADPH

63
Q

Summarize stage III of cholesterol biosynthesis

A

The cyclization of squalene via NADPH and oxidosqualene cyclase; eventual isomerization from lanosterol to cholesterol

64
Q

What lipoprotein is the major carrier of cholesterol in blood?

A

low density lipoprotein (LDL)

COB Biochemistry (12 decks)

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