Fatty Acid Metabolism Flashcards
What are three sources of lipid?
Fats consumed in the diet
Fats stored in cells as lipid droplets
Fats synthesized in one organ (liver) for transport to another organ
What is the function of acid resistant lingual lipases?
Secreted from glands under the tongue
Begins fat digestion in the stomach
What are gastric lipases?
Lipases that act in the stomach to digest fats
What is the function of pancreatic lipases?
To removie FA at carbons 1 and 3 of triglyceride
*different lipases for each
What is the function of colipase?
Anchors pancreatic lipase at the lipid-aqueous interface
Secreted as zymogen
What is the function of Cholesterol esterase?
Revmoves FA from cholesterol
Secreted from pancreas
How are phospholipids digested?
Phospholipase A2 removes FA from one carbon
Lysophospholipase removes FA at C1
What is the product of phospholipid digestion?
Glycerylphosphorylcholine
Exreted, further degraded, or absorbed
What is the function of Cholecystokinin (CCK)?
Hormone released from jejunum and duodenum
Acts on Gall bladder to release bile
Acts on pancreas to release enzymes from exocrine cells
What is the function of Secretin?
Produced in response to low pH of chyme
What are two consequences of lipid malabsorption?
Steatorrhea
Deficiency of lipid soluble vitamins ADEK
What is the function of Apolipoprotein C-II?
Activates lipoprotein lipase located on blood vessels
Part of chylomicrons
How are chylomicrons used by tissues?
Broken down in capillaries of skeletal muscle or adipose
How are Free fatty acids used by tissues?
Fuel or storage or transported to other cells
What is glycerol used for?
Used by liver to produce glycerol-3-phosphate for glycolysis or gluconeogenesis
How are chylomicron remnants used by the cell?
Endocytosed by liver and hydrolized.
Cholesterol and nitrogenous bases can be recycled
How are triglycerides transported from the lumen to the blood?
Broken down in lumen
Re-synthesized within the intestinal cell
TGs are excreted and transported in chylomicrons
What complications of CF are related to fat metabolism?
Growth Failure
Bone Disease
Deficiency of fat soluble vitamins
What is medium-chain acyl-CoA dehydrogenase (MCAD) deficiency?
Most common genetic defect in FA metabolism in US and Northern Europe
Mutation in enzyme
Causes vomiting, lethargy, hypoketosis, hypoglycemia
What are the three stages of processing for the utilization of fatty acids?
Mobilization
Activation and Transport to the mitochondria
Fatty acids broken down into acetyl-CoA
How are storage fatty acids signaled to be mobilized?
Hormone signalling triggers cAMP/PKA pathway that activates a triacylglycerol lipasae
What is the function of Perilipin?
Phosphorylated by PKA, increases access to lipids by permeabilizing the lipid droplet
What is the function of Fatty acyl-CoA synthetase?
Activates Fatty Acids by attaching CoA via ATP hydrolysis
What is the function of Carnitine acyltransferase I?
Attaches an activated FA to carnitine for transport into the mitochondria
CoA provides the energy for this reaction
What type of fatty acids can cross the mitochondrial membrane without carnitine?
Short or medium chain fatty acids
<12 C
How is carnitine obtained?
Meat
Synthesized from lysine and methionine by liver or kidney
What is the rate limiting step for FA oxidation?
Carnitine transport
What inhibits CPT-1?
Malonyl CoA
What things could result in carnitine deficiency?
Liver disease
Malnutrition or vegetarian diet
Increased requirement - burns, pregnancy
Hemodialysis
Congenital deficiency
What results from an inability to use LCFA as fuel?
Imparied ability to synthesize glucose furing a fast, possible hypoglycemia, coma and death
Impaired ability to sustain exercise
What are the three stages of Fatty acid oxidation?
Successive removal of two C units
Acetyl groups are oxidized to CO2 in the citric acid cycle
Electrons are donated to the mitochondrial respiratory chain to phosphorylate ADP to ATP
What is the order of reactions in fatty acid oxidation?
Oxidation–>Hydration–>Oxidation–>Thiolysis
What is produced during each round of FA oxidation removing two carbons?
1 FADH2 - first oxidation
1 NADH - second oxidation
1 Acetyl CoA - thiolysis reaction
How many ATP are formed from complete oxidation of palmitate (C16)?
106 ATP
What type of fatty acid does B-oxidation completely degrade?
Saturated fatty acids with an even number of carbons
What are the final products of B-oxidation of odd-number chain fatty acids?
Propionyl CoA and Acetyl CoA
What is the fate of Proprionyl CoA after B-oxidation?
Converted to succinyl CoA to enter the Citric acid cycle
What is the function of propionyl CoA carboxylase and what does it require?
Forms Methylmalonyl CoA from Propionyl CoA
Requires biotin
What does L-methylmalonyl–> succinyl CoA isomerization require?
Methylmalonyl CoA Mutase
Derivative of Vit B12 as coenzyme
What do unsaturated fatty acids with an odd number of double bonds require?
An additional isomerase that converts the cis double bond to a trans double bond
What do unsaturated fatty acids with an even number of double bonds require?
Reductase and isomerase
What is Refsum Disease?
Genetic deficiency in the peroxisomal enzyme responsible for one of the initial steps in the oxidation of phytanic acid
What are the symptoms of Refsum disease?
Retinities Pigmentosa
Progressive peripheral neuropathy
Skeletal malformation
Sever motor weakness
Where are very long, or branched chain fatty acids oxidized?
Peroxisomes
What are the four steps in a-oxidation for branched chains?
Activation with CoA
CoA and Formic acid released
Dehydrogenation
Activation with CoA, then B-oxidation releases propional CoA
What is Ketosis?
Ketone bodies are formed from Acetyl CoA when fat degredation predominates
What ketone bodies are formed during ketosis?
Acetoacetate
3-hydroxybutyrate
Acetone
How is ketogenesis regulated?
Entry of FA into oxidative pathway controlled by CPT-1
As level of FFA increases, more FFA converted to ketones
How does diabetes cause ketoacidosis?
Absence of insulin means liver cannot provide oxaloacetate
Insulin normally decreases fatty acid metabolism
Result is liver produces large amount of ketone bodies which are moderately strong acids
