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Saturday, August 11, 2018

Lipid Catabolism



Introduction of Lipid



           Lipid 
            A heterogeneous class of  naturally occuring organic compounds.

            In soluble in water but soluble in organic solvent.
   
         Lipid include:
            Open chain forms
            Cyclic forms

         Fatty acid
            An unbranced-chain carboxylic acid (12-20  carbons)

           ➔Unsaturated (C=C)
           ➔Saturated (C-C) 
         Amphipathic compounds (carboxyl group)
          ⏩Hydrophilic
          ⏩Hydrocarbon tails

          Derived from hydrolysis of:
          ⏩Animal fats
          ⏩Vegetable oils
          ⏩Phosphodiacylglycerols of biological membrane


         Triacyglycerols (TAG)
           ⏩An ester of glycerol with three fatty acids

          ➭Non polar
          ➭Major storage of fats in animal and plant
          ➭Yield higher energy than      glycogen
         Phospholipids (Polar & amphipathic)
            When one alcohol group of glycerol is esterified by a phosphoric acid rather than by a carboxylic acid.

         Phosphoglycerides
           ➭ The 2nd most abundant group of natural occurring lipid
           ➭Found in plant and animal membranes

         Waxes
           ➭A complex mixture of long-chain carboxylic acids and alcohols
           ➭As protective coatings for plants & animals
         Sphingolipids
           ➭Contain sphingosine
           ➭Long chain amino alcohol sphingosine
           ➭Found in plants and animals
           ➭Many in nervous system

         Glycolipid
           ➭A compound in which a carbohydrate   (sugar) is bound to an –OH of the lipid
           ➭ Most cases sugar is either galactose or glucose
         Steroids
             A group of lipids that have fused-ring structure of :
           ➭3 six-membered rings
           ➭1 five-membered ring
  
            The steroid of most interest in biological membranes is cholesterol


Lipid bilayer


The polar surface of the bilayer contains charged groups


The hydrophobic tails lie in the interior of the bilayer




Catabolism of Lipids 


⏩Lipase catalyze hydrolysis of bonds between FA and the rest TAG

⏩Phospolipase catalyze hydrolysis  of bonds between fatty acids and the rest of phosphocyglycerols





Fatty Acid Activation

⏩Fatty acid must be activated to design the B-Oxidation

⏩FA is linked to Acyl- Carrier protein (ACP) as the carrier of FA

⏩FA is activated with CoA-SH to form Fatty Acyl- CoA (required ATP > AMP) (~ 2 ATP)

occurs in the cytosol 

The Role of Carnitine in Acyl-CoA Transfer

⏩b-Oxidation occurs in the matrix of mitochondria. However, the fatty acyl-CoA
can only cross the outer mitochondrial membrane, but not the inner
membrane

⏩In the intermembrane space, the acyl group is  transferred to carnitine to 
form a cyl-carnitine

⏩Acyl-carnitine can cross the inner mitochondrial membrane via a specific
carnitine/acyl-carnitine  transporter.

⏩Once in the matrix, the acyl group is transferred from carnitine
mitochondrial-CoA-SH to form back fatty acyl-CoA.

⏩Fatty acyl-CoA will be then degraded via b-Oxidation in the matrix of
mitochondria .

B-oxidation

Occurs in the matrix of mitochondria.

➧The complete cycle of one b-oxidation requires 4 reactions:



Reaction 1:

Oxidation of the a,b carbon-carbon single bond to a carbon carbon double bond
Reaction 2:

Hydration of the carbon-carbon double bond

Reaction 3:

Oxidation of the b-hydroxyl group to a carbonyl group

Reaction 4: 

Cleavage (cleavage of the carbon chain to produce acetyl-CoA and an acyl CoA that is two
carbon shorter).

These cycle repeat 8 times

The complete cycle of one b-Oxidation produces:
•8 FADH
•8 NADH 
•9 acetyl-CoA (will enter the kreb cycle)
acyl-CoA


Kreb cycle






Total ATP in B-oxidation process


Reaction
NADH
FADH2
ATP
Activation step


-2
B-oxidation (8 cycle) produce (9 acetyl-CoA)
8
8

Processing of 9 acetyl-CoA Kreb cycle
27
9
9
Reoxidation of NADH in B-oxidation


20
Reoxidation of NADH in Kreb cycle


67.5
Reoxidation of FADH2 in B-oxidation


12
Reoxidation of FADH2 in Kreb cycle


3.5
Total ATP
120


Metabolic fates of acetyl-CoA

Major metabolic fates of acetyl-CoA:

1. ATP productions (enter kreb cycle à ETC)
2. Ketone bodies production
3. Fatty acid biosynthesis

4. Cholesterol biosynthesis


Ketone Bodies 

If an organism has an excess of acetyl-CoA, it produces ketone bodies.

Formation of ketone bodies occurs when the amount of acetyl-CoA produced
is excessive compared to the amount of oxaloacetate available in the kreb cycle.

This situation can arise from:
>Intake high in lipids and low in carbohydrates
>Diabetes not suitably controlled
>Starvation

•Ketone bodies are: acetone, b-hydroxybutyrate, and acetoacetate





Here are a few videos that helps you to understand Lipid catabolism:












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