fatty acid and phospholipid synthesis

what are lipids

molecules that are soluble in organic solvents and insoluble in water. mostly found in membranes

major functions of lipids

membrane structure

protein folding cofactors

energy storage

water retention (waxes)

signaling moleucles

electron transport

vitamin/steroid ligands

glycoconjugate synthesis

what is the structure of a fatty acid

carboxyl group (COOH) + long hydrocarbon chain

key features of fatty acids

amphiphillic (hydrophobic tail + hydrophillic head)

can be: un/saturated, branched, hydroxylated

what is typical about naturally occuring fatty acids

unbranched, even number of carbons, length: 4-28 carbons

do fatty acids exist freely in bacteria

no

they are always attached to: phospholipids, lipoproteins, LPS (lipid A)

why are unsaturated and branched fatty acids important

they increase membrane fluidity

fluid mosaic model

membrane consists of fluid phospholipid bilayer, embedded proteins, amphipathic structure

key interactions in membranes

hydrophobic interactions → tails avoid water

hydrophillic interactions → heads interact with water

micelle

spherical structure with hydrophobic tails inside and hydrophillic heads outside

what is a liposome

closed bilayer vesicle used as membrane models and in mRNA vaccines

where does fatty acid synthesis begin

Acetyl-CoA

what is the first step of fatty acid synthesis

formation of malonyl-CoA via acetyl-CoA carboxylase

what enzyme catalyzes the first step

Acetyl-CoA carboxylase

Acetyl-CoA carboxylase 3 components

Biotin carrier protein (BCP)

Biotin carboxylase

Carboxyltransferase

what reaction does Acetyl-CoA carboxylase perform

Acetyl-CoA → Malonyl-CoA

what is ACP

Acyl Carrier Protein- carries growing fatty acid chain

enzymes in fatty acid synthesis

ketoacyl ACP synthase, Ketoacyl ACP reductase, Hydroxyacyl ACP dehydratase, Enoyl ACP reductase

4-step fatty acid synthesis cycle

1. condensation

2. 1st reduction (NADPH)

3. dehydration

4. 2nd reduction (NADPH)

what happens each fatty acid synthesis cycle

adds 2 carbons

final product length of the fatty acid synthesis cycle

C16 (palmitate)

what does triclosan inhibit

enoyl-acp reductase (final reduction steps)

why is triclosan important

antimicrobial, targets fatty acid synthesis

how are unsaturated fatty acids made

1. alternate dehydratase pathway

2. desaturaase enzymes

what do desaturates do

convert saturated → unsaturated fatty acids

why is the conversion of saturated to unsaturated fatty acids important

adjusts membrane fluidity without making new lipids

starting molecule of phospholipid biosynthesis

glycerol-3-phosphate (G3P)

how is G3P made

from glycerol or from DHAP (glycolysis intermediate)

what is formed after 2 acylations

phosphatidic acid

How is phosphatidylethanolamine (PE) formed?

Serine added → phosphatidylserine

Then decarboxylated → PE

How is phosphatidylglycerol (PG) formed?

G3P added → PG

What is cardiolipin?

Formed from 2 PG molecules

Composition of E. coli membrane?

70% PE

25% PG

5% cardiolipin

Why target phospholipid synthesis?

Essential for membrane integrity

Disrupting them kills bacteria

Why is LPS important?

Forms outer membrane of Gram-negative bacteria

Protects bacteria from antibiotics

Why is LPS a drug target?

Essential for survival and virulence

What is beta-oxidation?

Breakdown of fatty acids → energy

Why is beta-oxidation important in bacteria?

Energy production

Metabolic flexibility

Main short-chain fatty acids (SCFAs)?

• Acetate

• Propionate

• Butyrate

SCFA ratio in colon?

60 : 20 : 20

Why are SCFAs important?

Lower pH (acidic environment)

Promote beneficial bacteria

Inhibit pathogens

Increase mineral absorption

What happens if bacteria lack key phospholipids (PE, PG, CL)?

Stress responses activated

Cells become unhealthy

Importance of beta-oxidation?

Energy generation from fatty acids

4-step fatty acid synthesis?

1. Condensation

2. Reduction

3. Dehydration

4. Reduction

Why are membrane phospholipids good drug targets?

Essential for survival and membrane integrity

Why is SCFA balance important?

Indicates gut health and microbial balance