Metabolism 6- Fatty Acids Flashcards
What is the end product of fatty acid metabolism and where does this take place
Acetyl CoA- which can enter the Krebs Cycle
This takes place in the mitochondrial matrix.
Describe the structure of fatty acids
Hydrophilic carboxyl head
Hydrophobic hydrocarbon tail
What are the features of unsaturated fatty acids
They contain one or more double bonds, giving the fatty acid chain a kink, this makes it more difficult for the fatty acids to pack together, hence unsaturated fatty acids are likely to be liquid at room temperature.
How are fatty acids stored within cells
They are stored as triacylglycerol- three fatty acids linked to a glycerol head group via an ester bond. In mammals, specialised cells known as adipocytes take on the role of the storage of fatty acids.
Where is fat derived from
De Novo synthesis in the liver
Diet
Storage depots in adipocytes.
Why are bile salts important
Fatty acids are insoluble and so cannot be transported in the blood stream. Bile salts (generated by the live and stored in the gall bladder) pass through the bile duct and into the small intestine, where they emulsify fats, aiding the digestion and absorption of fats as well as fat soluble vitamins (A,D,E and K)
What is a consequence of a lack of bile salts
A lack of bile salts results the majority of fat passing through the gut undigested and unabsorbed resulting in steatorrhea (fatty stool).
Describe the process of fat digestion and absorption
a - Lipid digestion by lingual gastric and pancreatic lipase results in the formation of Monoacylglycerol (MAG), diacylglycerol (DAG) and free FAs that are released by lipid hydrolysis join BS (Bile Salts), CL, (Cholesterol) lysophosphatidic acid (LPA) and fat-soluble vitamins to form mixed micelles.
b - Digested dietary products are absorbed by enterocytes that line the brush border of the small intestine. TAGs are resynthesized under the control of several enzymes prior to incorporation into chylomicrons (CM) and transportation
What is Orlistat
A potent inhibitor of gastric and pancreatic lipases.
It is a chemically synthesized derivative of lipstatin, a product of Streptomyces toxytricini.
Orlistat reduces fat absorption by 30% which is almost completely excreted by the faecal route.
Main side effects include abdominal pain, urgency to defecate, increased flatus and steatorrhea.
Which organ does not use energy from fatty acid oxidation
The Brain
What is the first step in the beta-oxidation of fatty-acids
They are converted into an acyl-CoA species
Fatty acid + ATP + Acetyl CoA — Acyl CoA + AMP + PPi
The reaction is catalysed by acyl CoA synthesase.
This reaction occurs on the outer mitochondrial membrane
Describe the reactions in the carnitine shuttle
Carnitine acyltransferase 1:
Acyl CoA + Carnitine — Acyl Carnitine + CoA
Translocase: Acyl Carnitine in. Carnitine out
Carnitine transferase II:
Acyl Carnitine + CoA — Acyl CoA + Carnitin
Describe simply the process of beta oxidation
The acyl CoA undergoes a sequence of oxidation, hydration, oxidation and thiolysis reactions (collectively called β-oxidation).
This results in the production of one molecule of acetyl CoA and an acyl CoA species which is 2 carbons shorter than the original.
What are the products of each cycle
The β-oxidation reactions continue to consecutively remove 2-carbon units from the acyl CoA thereby producing acetyl CoA.
On the final cycle (4-carbon fatty acyl CoA intermediate), two acetyl CoA molecules are formed.
During each cycle one molecule each of FADH2 and NADH are produced.
Odd chain fatty acids give propionyl CoA and Acetyl CoA on the final cycle. Propionyl CoA undergoes a series of reactons to yield succinyl CoA which enters the TCA cycle.
Describe the first reaction of beta oxidation
Fatty acyl dehydrogenase adds a double bond between the second and third carbon atoms. FADH— FADH2
Describe the second reaction of beta oxidation
Hydration of this compound to give 3-hydroxyacyl CoA.
This reaction is catalysed by 3-Hydroxyacyl CoA hydrolase.
Describe the third reaction of beta oxidation
3-hydroxyacyl CoA undergoes an oxidation reaction, where a ketone is produced, catalysed by L- Hydroxyacyl CoA dehydrogenase
Describe the final reaction of beta oxidation
Beta ketothiolase hydrolyses thioester bond of HS- CoA which joins to give Acyl CoA, removing Acetyl CoA.
When will the Acetyl CoA generated by beta oxidation enter the Krebs Cycle
Acetyl CoA generated by β-oxidation enters the TCA cycle only if β-oxidation and carbohydrate metabolism are balanced, since oxaloacetate is needed for entry
When will fat breakdown predominate
during fasting or in diabetes, gluconeogenesis will take oxaloacetate to generate glucose. Hence the need for ketonebodies. Non-enzymatic decrboxylation of Acetoacetate gives acetone. Occurs in the liver. This increases the acidity of the blood.
Describe the reactions involved in the production of ketone bodies.
Reaction 1:
Condensation of two acetyl CoA molecules to give acetoacetyl CoA. Catalysed by 3-ketothiolase. CoA group released
Reaction 2:
Acetoacetyl CoA + Acetyl CoA + H2O — 3-hydroxy-3-methyl glutaryl CoA. Catalysed by hydroxymethylglutaryl CoA synthase
Reaction 3:
Removal of acetyl CoA from 3-hydroxy-3-methyl glutaryl CoA to give acetoacetone. Catalysed by hydroxymethyl CoA cleavage enzyme.
Reaction 4: Spontaneous breakdown of acetoacetone into acetone. Acetoacetone can also be oxidised to 3-hydroxybutyrate by D-3 hydroxybutyrate dehydrogenase. NAD—NADH. This reaction is reversible.
What enzymes are involved in lipogenesis
Acetyl CoA Carboxylase
Fatty acid synthase (FAS) - polypeptide with seven different enzymatic activities.
When is lipogenesis required
Most fatty acids obtained from a Western diet. Some synthesis needed during embryogenesis and also within mammary gland during lactation.
Describe reaction 1 of lipogenesis
Acetyl CoA + HCO3- + ATP — Malonyl CoA (3C) + ADP +Pi. Catalysed by Acetyl Co-A carboxylase
