Chpt 22-Fatty Acid Metabolism Flashcards

1
Q

Fatty Acid Function

A

1) Fuel-stored as Triacylglycerol (FAT)
2) Synthesis of Phospholipids and Glycolipids (membranes)
3) Modify Proteins
4) Synthesis of Hormones

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2
Q

Fatty Acid Structure

A

Large Hydrocarbon chain termination at Carboxylate group

-saturate/unsaturated

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3
Q

Triacylglycerol (FAT)

-function

A

Energy Dense form of energy storage

-reduced and anhydrous

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4
Q

Triacylglycerols

-Structure

A

Uncharged esters of fatty acids with glycerol group

-Glycerol + 3 Fatty Acids

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5
Q

Triacylglycerols are stored in?

A
  • cytoplasm of adipose tissue(Fat) cells for mobilization to blood stream
  • Muscle cells for generation of ATP (Marbled steak)
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6
Q

Fatty Acid Degredation/Synthesis

-general characteristics

A

Requires Four steps

  • Cataboism vs Anabolism
  • Reactions are not reverse
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7
Q

Digestion of Dietary Lipids

  • Digested by?
  • Where?
  • Absorbed?
A

Dietary Triacylglycerol digested by PANCREAS LIPASES
-removes 2 fatty acids by hydrolysis in sequential steps from glycerol producing monoacyglycerol

Where? In the Intestinal Lumen
-Triacylglycerols are incorporated into micelles with bile salts

Fatty acids and monoacylglycerol absorbed into mucous cells

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8
Q

Bile Salts

A

Synthesized from cholesterol in liver

-secreted from gall bladder

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9
Q

Steatorrhea

A

Disease due to production of insufficient mucosal cells

-fat excrete in feces

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10
Q

Fatty Acid Catabolism 4 General Steps:

A

1) Oxidation
2) Hydration
3) Oxidation
4) Cleavage

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11
Q

Fatty Acid Anabolism 4 General Steps:

A

1) Reduction
2) Dehydration
3) Reduction
4) Condensation

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12
Q

Transportation of dietary lipids

A

After we breakdown the lipids, we transport them across the membrane and into mucosal cells
-Triacylglycerols are resynthesized and assembled into chylomicrons

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13
Q

Triacylgylcerol used to produce ATP

A

Triacylglycerols mobilized from adipose tissue (fat cells) by hormonal (Epinephrine/Glucagon) controlled reaction
1) Glycerol enters the blood and is carried to the liver
and is converted to pyruvate or glucose through glycolysis or gluconeogenesis
2) Fatty acids are attached to albumin enter the blood and travel to mitochondria of tissue that:
-oxidized fatty acids to Acetyl CoA, NADH, or FADH2
-AND oxidizes Acetyl CoA in Krebs cycle to Co2, NADH, and FADH2

WHICH CAN ALL BE CONVERTED to ATP

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14
Q

Triacylglycerol Lipase

A

Releases fatty acids from triacylglycerol stored in adipose tissue (NOT the same mechanism as dietary lipids)

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15
Q

Triacylglycerol Lipase

-Hormone Control

A

Hormone Control:

1) Epinephrine/Glucagon increases activity of Signal Transduction pathway involving:
- Bind to 7TM
- G Protein
- Adenylate Cyclase-synthesizes ATP
- Protein Kinase A
- PERLIPIN A
- Triacylglycerol Lipase

Phosphorylation turns Triacylglycerol Lipase FON

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16
Q

Perlipin A

-function

A

remodels fat droplets making fatty acids more accessible

17
Q

Fate of Glycerol

A

Can either enter Glycolysis or Gluconeogenesis
-since in liver think of Gluconeogenesis

1) Glycerol Kinase
Glycerol-> L-Glycerol 3-Phosphate at the expense of ATP
2) Glycerol Phosphate Dehydrogenase
Glycerol 3-Phosphate -> DHAP and G3P at the expense of NAD+
-feeds into glycolysis or gluconeogenesis

18
Q

What does Beta Oxidation of Fatty Acids Produce Overal

A

Acetyl CoA (2 carbon unit)
NADH
FADH2

19
Q

Activation of Fatty Acids

A

Two step process:

  • activates Fatty acid by attachment to CoA via Thioester bond
  • occurs in the cytoplasm of theouter mitochondrial membrane

1) Fatty Acid + ATP-> Acyl Adenylate + PPi
- catalyzed by Acyl Adenylate
- hydrolysis of PPi drives the reaction

2) Acyl Adenylate + HS-CoA-> Acyl CoA + AMP
- catalyzed by Acyl CoA Synthetase

20
Q

Acyl CoA Transferred into Mitochondria

-Enzymes involved

A

1) Carnitine acyltransferase I
2) Carnitine Translocase
3) Carnitine acyltransferase II

21
Q

Carnitine Acyltransferase I

A

Helps transfer Acyl CoA into Mitochondria

Transfers Fatty acid from S of CoA to the Hydroxyl O of Carnitine
-Located in inter membrane space of mitochondria

22
Q

Carnitine Translocase

A

Helps transfer Acyl CoA into Mitochondria

Transfers Acyl Carnitine across intermitochondrial membrane
-located as transmembrane protein of inner mitochondrial membrane

23
Q

Carnitine Acyltransferase II

A

Helps transfer Acyl CoA into Mitochondria

Converts Acyl Carnitine to Acyl CoA
-located in matrix

24
Q

Beta Oxidation of Fatty Acids

-1st Oxidation Step

A

Acyl CoA-> trans Enoyl CoA

  • catalyzed by acyl CoA dehydrogenase
  • Acyl CoA is oxidized forming a double bond between alpha and beta carbon
  • FAD is reduced to FADH2 and electrons enters ETC

3 Forms of Enzyme:

  • Long Chain (12-18 Carbons)
  • Medium Chain (4-14 Carbons)
  • Short Chain (4-6 Carbons)
25
Q

Beta Oxidation of Fatty Acids

-Hydration Step

A

trans Enoyl CoA-> L-3-hydroxyacyl CoA

  • catalyzed by Enoyl CoA hydrates
  • stereospecific hydration of double bond (OH=double bond)
26
Q

Beta Oxidation of Fatty Acids

-2nd Oxidation Step

A

L-3-hydroxyacyl CoA -> 3-ketoacyl CoA

  • catalyzed by L-3-hydroxyacyl CoA
  • beta carbon oxidized to Keto group
  • NAD+ reduced to NADH
27
Q

Beta Oxidation of Fatty Acids

-Cleavage Step

A

Thiolysis STEP
3-Ketoacyl CoA-> Acyl CoA + Acetyl CoA
-catalyzed by B-ketothiolase
-CoA-SH attacks Beta Carbon carbonyl cleaving/releasing Acetyl CoA

28
Q

Beta Oxidation of Unsaturated Fatty Acids

-Enzymes Used

A

Enzyme used depends on the location of the double bond

1) double bond beginning with odd number
- Isomerase ONLY-shifts double bond to even number carbon
- cis Delta (X) Enoyl CoA Isomerase

2) Double bond beginning with even number
- Reductase AND Isomerase
- 2,4-dienoyl CoA reductase-> Used NADH to reduce even number double bonds
- cis Delta (X) Enoyl CoA Isomerase

29
Q

What is the Result of Beta Oxidation of Unsaturated Fatty Acids

A
Propionyl CoA  (3 Carbons)
-rearrangement of these 3 carbon units leads to them entering Krebs cycle

1) Propionyl CoA-> D-methylmalonyl CoA
- Carboxylation by propionyl CoA Carboxylase at the expense of ATP
- biotin=prosthetic group
2) D-methylmalonyl CoA-> Succinyl CoA
- Isomerization by methylmalonyl CoA mutase **
- exchanges H and CO-S-CoA using homolytic cleavage
- Forms a CH2 radical that abstracts H from substrate
- coenzyme-vit B12=Cobalamin

30
Q

Vitamin B12

-Structure

A
Structure:
Corrin Ring with Central Cobalt atom:
Cobalt forms 6 coordinate bonds to:
-4 to N of pyrrole units
-1 to 5' deoxyadenosyl unitss
-1 to dimethylbenzimidazole unit (usual) or cyano, methyl, or other ligand unit
31
Q

Vitamin B12

-used in?

A

1) Intramolecule Reactions
2) Methylations
- Synthesis of Methionine
- reduction of ribonucleotides into deoxyribonucleotides

32
Q

What two enzymes in mammals use the coenzyme Vit B12

A

1) Methylmalonyl CoA Mutase

2) Methionine Synthase or homocysteine methyltransferase

33
Q

Another name for Vit B12

A

Cobalamin

34
Q

Peroxisomes also oxidize Fatty Acids

A

Oxidize long fatty acids to Octanoyl CoA

  • electrons transfered from O2 yielding H2O2 which is a ROS that is detoxified by catalase
  • Peroxisomes contain isozymes of mitochondrial enzymes
35
Q

Zellweger Syndrome

A

Syndrome due to abnormal function of peroxisomes

36
Q

Fats burn in the flame of Carbohydrates

A

Acetyl CoA from Fatty Acid Oxidation enters Kreb’s Cycle only if fat and carbohydrate degradation is balanced

1) to enter Krebs cycle Acetyl CoA must combine with OAA
- OAA concentration is dependent on presence of carbohydrate oxidation
- During fasting (or Diabetes) OAA is bled off and converted to pyruvate to synthesize glucose in gluconeogenesis. During Gluconeogenesis the rate of Krebs cycle slows

37
Q

Ketone Bodies

A

Formed during fasting or diabetes from acetyl CoA produced in Beta Oxidation of Fatty Acids

  • Ketone bodies are Acetoacetate, D-3-hydroxybutyrate, and Acetone found in blood
  • synthesized in the liver
38
Q

What Enzymes are used to form ketone bodies?

-OVeral Mechanism

A

1) 2x Acetyl CoA -> Acetoacetyl CoA + CoA
- catalyzed by 3-ketothiolase

2) Acetoacetyl CoA+ (3rd) Acetyl CoA + H2O ->3-hydroxy-3-methyl-glutaryl CoA (HMG)
- catalyzed by hydroxymethylglutaryl CoA synthase

3) HMG (5C) -> AcetoAcetate (4C)
- catalyzed by hydroxymethylglutaryl CoA cleavage enzyme
- releases Acetyl CoA

2 Fates for Acetoacetate (4)

4) Acetoacetate-> D-3-hydroxybutyrate
- catalzyed by D-3-hydroxybutyrate dehydrogenase
- NADH oxidized to NAD+
5) Acetoacetate-> Acetone
- spontaneously decarboxylates to Acetone
- amount of acetone produced is proportional to the amount of acetoacetate in the blood

39
Q

Acetoacetate-> 2 Acetyl CoA

-reconvertd?

A

Ketone bodies are released from liver, because liver lacks the CoA transferase

2 Steps:

1) Acetoacetate-> Acetoacyl CoA
- CoA transferase
- at the expense of Succinyl CoA-> Succinate (oxidized)
2) Acetoacyl CoA + CoA-> 2 Acetyl CoA
- Thiolase