Lipid Biosynthesis

Eicosanoids

Active localized intercellular messengers derived from arachidonic acid

Derived from linoleate in response to hormones/ other stimuli

Malonyl-CoA

Formed from Acetyl-CoA and bicarbonate using acetyl-CoA carboxylase

Malonyl-CoA units along with initial acetyl group and multienzyme FA synthase complex forms FAs

Palmitate

A 16C saturated FA

Step 1: Condensation w/ Acetyl group

An activated acetyl group condenses with a malonyl group

Step 2: Reduction

Step 3: Dehydration

Step 4: Reduction

Reduction of C-3 carbonyl group, closest to alkyl group

Occurs at C-2 and C-3

Double bond is reduced

A 3C intermediate

Contains biotin

Acetyl-CoA carboxylase

Inhibited by palmitoyl-CoA

Palmitoyl-CoA

Final product of lipid biosynthesis

FA Synthesis

FA Degradation

Fatty Acids

What are FAs?

What components are required to make FAs?

When are FAs synthesized?

In what form are they normally found?

When?

When are FAs degraded?

What?

Where?

Where can FAs be found?

Where are FAs synthesized?

Where are FAs degraded?

Mainly in the cytoplasm of liver cells

In the mitochondrial matrix of liver cells

They are stored In adipocytes of adipose tissue

An oxidative process

GOAL: Converts fatty acids into activated acetyl CoA groups

Acetyl CoA units then move into the TCA cycle/Citrate Cycle to combine with OAA

They are normally found in 3's in TAGs (Triacylglycerols)

How to make acetyl CoA units?

Step 1: Obtain an activated FA

Step 2: Oxidize the αβ bond in the FA from a single bond to a double bond

Step 3: Hydrate the αβ double bond to introduce a hydroxyl on the β carbon

Step 4: Oxidize the hydroxyl into a ketone

Step 5: Cleave the FA into an activated acyl group and acetyl group via thiolysis

CoA cleaves this FA

Acetyl CoA, malonyl CoA, acetyl CoA carboxylase, FA synthase, thiols,

Why are they important for living organisms?

2. They are the building blocks of other lipids

1. They act as fuel molecules, being stored in TAGs in adipocytes

3. They serve as membrane anchors, binding and directing proteins to the membrane

4. They serve as intracellular signaling molecules and hormone derivatives

Eicosanoids, derived from the linoleate-derived 20:4 arachnidonic acid, are examples and are synthesized in most human tissues

Biochemical lipids

Glycophospholipids

Eicosanoids

Fats

Triacylglycerols (TAGs)

Can come from the diet

1. Digested by intestinal lipases, prod. by the pancreas

Why?

Because the intestinal epithelium can only absorb FAs

Most ingested lipids are TAGs

Come from emulsified (by bile salts like glycocholate) lipids in the stomach

Glycerol head points towards the bile salt particle surface in for lipids to be easily...

Phosphatidate = its precursor

Also the precursor for glycophospholipids and phosphatidyl lipids

Converted to DAG using phosphatidic acid phosphatase (PAP)

DAG (diacylglycerol) converted to phosphatidate using DAG kinase

Protein colipase must bind to lipase first in order for lipase to bind to the bile salt particle

2. TAGs reformed in these micelles and packaged into...

Chylomicrons

Stable Lipoprotein transport particles (LPTPs)

2000 Angstroms in diameter

TAGs + proteinaceous apo-B48 = inside of chylomicrons

Can transport Vitamins KADE and cholesterol

3. Go iinto--> lymph---> blood

4. Bind to membrane lipases @ adipocytes and muscle cells

5. Undergo degradation for tissue transport, then resynthesis inside muscle cell/adipocyte

Oils

Jojaba oil cannot contribute to weight gain because they cannot be degraded properly in the intestine

Lipases

Once stimulated by hormones, they can hydrolyze TAGs

Requires three stages

1. Mobilization of TAGs via hormones

2. Activation of FAs for transport into mitochon. matrix

3. Beta oxidation of FAs

3. Beta oxidation of FAs

Includes ATGL (TAG-->DAG) and HS-lipases (DAG-->MAG) and MAG lipases (MAG --> FA + glycerol)

Stimulated by epinephrine and or glucagon binding 7TMR