PHR912: LIPID METABOLISM 1

BLOCK 4 WEEK 1

TB and Bacterial Lipid Metabolism:

Large fatty acids play a unique role in the encasulation process of Mycobacterium tuberculosis

Lipids:

Family of biomolecules that are soluble in organic solvents but not water

Esters of fatty acids:

Triacylglycerols, phospholipids

Steroids: 

consist of 4 fused carbon rings.

three 6 membered rings + one 5 membered ring

Can steroids be broken down?

no

Esters of fatty acids examples:

Triacylglycerols

phospholipids (glycerophospholipids)

sphingolipids

oils, waxes, fats

Steroid molecules:

Cholesterol

Steroid hormones

Bile acids

Special lipids:

Eicosanoids

fat soluble vitamins

functions of lipids:

store energy (triglycerides)

major components of cell membranes (phospholipids)

serve as chemical messengers (hormones)

help digestion (bile acids)

anchor proteins to membranes (lipoprotein receptors)

Insulate nerves and protect internal organs

Short chain fatty acids:

2-4 carbons

Medium chain fatty acids:

4-12 carbons

Long chain fatty acids:

12-20 carbons

Very long chain:

>20 carbons

What molecule is this

omega 3

Fatty acids are:

Major source of energy for ATP synthesis

What cells cannot use fatty acids as fuels:

red blood cells and brain

What is the most common saturated fatty acid?

Stearic acid

Unsaturated fatty acids are what and contain what?

Not linear and contain kinks due to double bonds

Multi-unsaturated fatty acids are what to our body?

Essential, thus are like vitamins

What fatty acid is this

oleic acid

what fatty acid is this

linoleic acid

What kind of bond connects the glycerol backbone to the fatty acid?

Ester bond

Triacylglycerols are:

Triesters of glycerol and three fatty acids

Glycerophospholipids:

Similar to triaclglycerols, but one of the hydroxyl groups of glycerol is esterified with a phosphoric acid aminoalcohol ester

Consists of a glycerol backbone, two fatty acid residues, a phosphate and a polar head group.

what molecule is this

glycerophospholipid

Glycerophospholipids contain what kind of tail and head

Lipophilic tail and hydrophilic head

Phospholipids are the

Backbone of cell membrane

Liposomes are:

Vehicles for drug delivery

Single bilayer

Lecithin is an important what:

Glycerophospholipid

Sphinoglipids are the only:

Membrane phospholipids not dervied from glycerol

What is the backbone of a sphingolipid?

Sphingosine

Eicosanoids:

Hormone-like substances produced from the C₂₀ -fatty acid arachidonic acid (AA)

‘local hormones’

Where are eicosanoids needed?

produced in low amounts at the location in the body where they are needed and broken down rapidly

What do eicosandoids do

Regulate blood pressure, contraction and relaxation of smooth muscle, inflammation, pain, fever, blood coagulation, reproduction, and bronchoconstriction, regulates cellular metabolism

MOA: NSAIDS:

blocks PGH₂ synthase (COX), the enzyme that converts AA to prostaglandins

Vitamin A supports what:

vision, growth, and differentiation

Vitamin K supports what:

Blood clotting

Vitamin E supports what

antioxidants

vitamin d supports what

calcium metabolism regulator

immune system modulator

Which vitamin is this

retinol

vitamin A

which vitamin is this

vitamin k

phylloquinone

which vitamin is this

vitamin a

Which vitamin is this

vitamin D

Cholecalciferol

Steroids:

Cholesterol

Steroid hormones

bile acids

Purpose of cholesterol:

Membrane stability

Precursor for steroid hormones and bile acids

Important in membranes, liver, and skin

a late precursor of cholesterol is also a precurosr for vitamin D3

What do steroid hormones do:

Regulate growth, metabolism, and reproduction

What do bile acids do

Are involved in lipid digestion and absorption

Steroid structure:

Backbone is a tetracyclic C17-alkane consisting of three 6-membered and one 5-membered ring (sterane)

What is this molecule

steroid

what molecule is this

cholesterol

Hormones:

Chemical messengers that provide communication from one part of the body to another

Corticoadrenal hormones:

Corticoids: downregulation of proinflammatory cytokines

Where are triacylglycerols (TG) mainly digested

in the intestine

What enzyme breaks down triacylglycerols in the intestine

Pancreatic lipase

Products of the breakdown of triacylglycerols

2 fatty acids and a 2-monoacyl-glycerol

Fatty acids of 12 carbons or less are digested:

Hydrolyzed by lipases from the mouth or stomach

what ester bonds get cleaved by the lipase during the first step of lipid degradation?

1 and 3 ester

Monoacylglycerol is used to:

Resynthesize a triacylglycerol

Fatty acids are degraded through:

Beta-oxidation and acetyl-CoA

Glycerol can be converted to what via what

Glucose via gluconeogenesis

Bile acids:

Emulsify dietary fats in the intestine- necessary for digestion to occur

Essential for the absorption of the digestion products of lipids

Recycled

Amphipathic-detergent like molecules

Cholesterol derivatives

Glycine or taurine conjugates

Structure of bile acids:

Cholesterol derivatives with 2 variable residues

Lipases are:

Special esterases

Pancreatic lipase:

A triacylglycerol lipase

Responsible for the digestion of triacylglycerols in the intestine, operating at pH 6

What is secreted along with pancreatic lipase

colipase and bicarbonate for neutralizing stomach acid until pH 6 is reached

Colipase:

binds to both the fats and the triacylglycerol lipase

ex: pancreatic lipase, making it more active

What does pancreatic lipase hydrolyze?

fatty acids from positions 1 and 3 of the glycerol backbone

Phospholipases:

Digest phospholipids

Free fatty acids and 2-monoacylglycerols are packaged:

Into micells with other dietary lipids, and emulsified by bile acids

Where do the micelles go after fatty acids and 2-monoacylglycerols are packaged into them?

Travel to the surface of intestinal epithelial cells, where everything MINUS the bile acids are absorbed

Where do bile acids get absorbed?

In the ileum via recycling

do short and medium length fatty acids (4-12 carbons) require bile acids for absorption?

NO

Micelle structure:

Monolayer membrane

outside: water

inside: lipid

Small

Lipsome structure:

Bilayer membrane

outside: water

Inside: water

relatively large

How are triacylglycerols recycled?

Within epithelial cells (enterocytes)

Fatty acids activated by acetyl CoA

Recombined with 2-monoacylglycerol

Forming triacylglycerols in the smooth ER

Dietary lipids are packaged into what for transport?

Chylomicrons in intestinal epithelial cells

Lipids can also be synthesized from:

Carbohydrates in the liver

Lipids who were synthesized in the LIVER travel via how?

Packaged into VLDLs (very low density lipoprotein)

Why are lipoproteins like chylomicrons and VLDLS necessary

Transport of lipids to prevent the accumulation of insoluble fat droplets in the blood

What increases the water solubility of lipoproteins?

amphipathic phospholipids on the surface of the lipoprotein

What is the major apoprotein of chylomicron

B-48

What is the major apoprotein of VLDL

B-100

Where are the protein components of a lipoprotein synthesized in

rough ER

Where does synthesis of TGs occur:

Smooth endoplasmic reticulum (SER)

Where does apoprotein synthesis occur

rough endoplasmic reticulum (RER)

Assembly of chylomicrons occurs where

Golgi complex

TG + Apoprotein =

Chylomicron

Finished chylomicron enters what

lymph through exocytosis

Chylomicron retention:

Inhereited disorder impairing the normal absorption of fats, cholesterol, and fat-soluble vitamins

Begins in infancy or early childhood

Symptoms of chylomicron retention

slow growth

slow weight gain

requent and chronic diarrhea

steatorrhea (fat in stool)

What gene is affected in Chylomiron retention

SAR1B whose product promotes the transport of pre-chylomicrons in micelles

Mutations cause retention of chylomicrons within endothelial cells and prevent release into bloostream- lipid droplets accumulate

Chylomicrons are secreted by:

Exocytosis into the lymphatic system, and then to the blood via the thoracic duct

Chylomicrons require what to become “mature”

HDL

apoE:

Recognized by membrane receptors

apoC_II

Activator of LPL (lipoprotein lipase)

What digests the triacylglycerols of the chylomicrons?

Lipoprotein lipase (LPL) attached to the proteoglycans of capillary epithelial cells

When the triacylglylcerols of the chylomicrons are broken down:

Resuliting fatty acids are taken up by adipose (most often) and muscle (less often) and stored in the adipose or beta-oxidized for energy (within muscle)

Glycerol is recycled in the liver during:

Fed state

Glycerol is used for gluconeogenesis in:

Fasting state

Cylomicron remnants are taken up and recycled by what:

Liver