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 FADH2 

•8 NADH 

•9 acetyl-CoA (will enter the kreb cycle)

•1 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:

Lipid Anabolism

Lipid Anabolism (biosynthesis of fatty acid)

Category of biochemical reaction	Anabolism
Pathway location	Cytosol
Types of redox reaction	Reduction
Shuttle mechanism	Citrate shuttle
Electron carrier	NADPH

FATTY ACID SYNTHESIS

• reduction process that build up the hydrocarbon chain of fatty acids utilizing activated acyl unit and malonyl unit.
• occur in cytoplasm
• catalyzed by fatty acid synthase containing 7 catalytic sites.
• incorporates carbon atoms from acetyl coA into growing fatty acid
• reverse process of degragation of fatty acid 

          condensation 👉 reduction 👉dehydration 👉reduction

• driven by the release of CO2 in a decarboxylation step.
• energetically unfavourable process
• reduction procss involved NADPH
• extension of fatty acid chain stops at 16C (saturated palmitate)

Location of acetyl coA into cytosol

🠟

 Activation of acetylcoA to malonyl coA

🠟

Synthesis of fatty acid chain via addition of activated acetyl coA

LOCATION OF ACETYL coA INTO CYTOSOL

CITRATE SHUTTLE : Acetyl CoA transporter

ACETYL CoA ➖ CITRATE

IN CYTOSOL- CITRATE ➖ ACETYL CoA

so now here is a little bit of calculation, in this process we need to produce 16C 

• in every 1 acetyl-coA transported into the cytosol, 1 NADPH form
• here we are making palmitate (16C), so we need 8 acetyl-coA(2C)
• 8 transported acetyl coA= 8 NADPH
• the other 6 NADPH will be produced by THE PENTOSE PHOSPHATE PATHWAY

ACTIVATION OF ACETYL CoA TO MALONYL COA

•  initiation of fatty acid synthesi
• formation of malonyl coA trough the irreversible carboxylation of acetyl coA
• a co2 is attached to acetyl coA producing a 3C molecule

SYNTHESIS OF FATTY ACID CHAIN VIA THE ADDITION OF ACTIVATED ACETYL-COA

This elongation of fatty acid chain start with formation of malonyl ACP and acetyl ACP

FATTY ACID SYNTHESIS

condensation

• the acetyl group moves from cystein residue onto malonate group on ACP
• product : acetoacetyl attached to ACP, CO2 released

reduction

• acetoacetyl is tranformed to D-3 hydroxybutyryl by con verting the carbonyl group into alcohol group
• reducing agent : NADPH + H+ 🠆 NADP+
• catalyzing enzyme : 𝞫-ketoacyl-ACP reductase

dehydration

• removal of hydroxyl group as H2O and formatiom pf C=C
• catalyzed by 3-hydroxyaxyl-ACP dehydratase

reduction by NADPH

• butyryl group is generated on ACP
• NADPH reduced the C=C because the ultimate fatty acid chain produced is a saturated fatty acid
• this completes the first elongation process containing 4C carbon.

the next 6 cycle produced 2C, total cycle is 7. palmitate (16C) is produced.

CHOLESTEROL BIOSYNTHESIS

• cholesterol only synthesize in animal
• cholesterol and steroid are synthesized from 2 acetyl-coA
• ISOPRENE units are the key to the biosynthesis of steroid and other biomolcules
• cholesterol is precursor for bile salts and a number of steroid hormones

LIPOPROTEIN

DETAILS OF HOW THE LIPIDS ARE TRANSPORTED IN THE BLOOD STREAM

CHOLESTEROL CAN LEAD TO THE HEART DISEASE