Chpt 22-Fatty Acid Metabolism Flashcards
Fatty Acid Function
1) Fuel-stored as Triacylglycerol (FAT)
2) Synthesis of Phospholipids and Glycolipids (membranes)
3) Modify Proteins
4) Synthesis of Hormones
Fatty Acid Structure
Large Hydrocarbon chain termination at Carboxylate group
-saturate/unsaturated
Triacylglycerol (FAT)
-function
Energy Dense form of energy storage
-reduced and anhydrous
Triacylglycerols
-Structure
Uncharged esters of fatty acids with glycerol group
-Glycerol + 3 Fatty Acids
Triacylglycerols are stored in?
- cytoplasm of adipose tissue(Fat) cells for mobilization to blood stream
- Muscle cells for generation of ATP (Marbled steak)
Fatty Acid Degredation/Synthesis
-general characteristics
Requires Four steps
- Cataboism vs Anabolism
- Reactions are not reverse
Digestion of Dietary Lipids
- Digested by?
- Where?
- Absorbed?
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
Bile Salts
Synthesized from cholesterol in liver
-secreted from gall bladder
Steatorrhea
Disease due to production of insufficient mucosal cells
-fat excrete in feces
Fatty Acid Catabolism 4 General Steps:
1) Oxidation
2) Hydration
3) Oxidation
4) Cleavage
Fatty Acid Anabolism 4 General Steps:
1) Reduction
2) Dehydration
3) Reduction
4) Condensation
Transportation of dietary lipids
After we breakdown the lipids, we transport them across the membrane and into mucosal cells
-Triacylglycerols are resynthesized and assembled into chylomicrons
Triacylgylcerol used to produce ATP
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
Triacylglycerol Lipase
Releases fatty acids from triacylglycerol stored in adipose tissue (NOT the same mechanism as dietary lipids)
Triacylglycerol Lipase
-Hormone Control
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
Perlipin A
-function
remodels fat droplets making fatty acids more accessible
Fate of Glycerol
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
What does Beta Oxidation of Fatty Acids Produce Overal
Acetyl CoA (2 carbon unit)
NADH
FADH2
Activation of Fatty Acids
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
Acyl CoA Transferred into Mitochondria
-Enzymes involved
1) Carnitine acyltransferase I
2) Carnitine Translocase
3) Carnitine acyltransferase II
Carnitine Acyltransferase I
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
Carnitine Translocase
Helps transfer Acyl CoA into Mitochondria
Transfers Acyl Carnitine across intermitochondrial membrane
-located as transmembrane protein of inner mitochondrial membrane
Carnitine Acyltransferase II
Helps transfer Acyl CoA into Mitochondria
Converts Acyl Carnitine to Acyl CoA
-located in matrix
Beta Oxidation of Fatty Acids
-1st Oxidation Step
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)
Beta Oxidation of Fatty Acids
-Hydration Step
trans Enoyl CoA-> L-3-hydroxyacyl CoA
- catalyzed by Enoyl CoA hydrates
- stereospecific hydration of double bond (OH=double bond)
Beta Oxidation of Fatty Acids
-2nd Oxidation Step
L-3-hydroxyacyl CoA -> 3-ketoacyl CoA
- catalyzed by L-3-hydroxyacyl CoA
- beta carbon oxidized to Keto group
- NAD+ reduced to NADH
Beta Oxidation of Fatty Acids
-Cleavage Step
Thiolysis STEP
3-Ketoacyl CoA-> Acyl CoA + Acetyl CoA
-catalyzed by B-ketothiolase
-CoA-SH attacks Beta Carbon carbonyl cleaving/releasing Acetyl CoA
Beta Oxidation of Unsaturated Fatty Acids
-Enzymes Used
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
What is the Result of Beta Oxidation of Unsaturated Fatty Acids
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
Vitamin B12
-Structure
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
Vitamin B12
-used in?
1) Intramolecule Reactions
2) Methylations
- Synthesis of Methionine
- reduction of ribonucleotides into deoxyribonucleotides
What two enzymes in mammals use the coenzyme Vit B12
1) Methylmalonyl CoA Mutase
2) Methionine Synthase or homocysteine methyltransferase
Another name for Vit B12
Cobalamin
Peroxisomes also oxidize Fatty Acids
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
Zellweger Syndrome
Syndrome due to abnormal function of peroxisomes
Fats burn in the flame of Carbohydrates
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
Ketone Bodies
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
What Enzymes are used to form ketone bodies?
-OVeral Mechanism
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
Acetoacetate-> 2 Acetyl CoA
-reconvertd?
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
