Ocular Biochem: Lipids

What is the solubility of lipids like?

-water insoluble and hydrophobic

-soluble in nonpolar solvents: benzene, chloroform, and hexane

When do lipid esters of fatty acids and glycerol associate together?

when present in polar solvents

What is the polarity of lipids?

partially polar at one end of their structure

What type of property do lipids have?

-has amphiphatic property: both hydrophilicty and hydrophobicity

-this property is very useful in cell membrane (both properties are needed)

What is the classification of lipids based on?

the chemistry and chemical properties of the lipids

What are the most important lipid classes?

-fatty acids

-triglycerols

-phospholipids

-isoprenoids

-esters

-eicosanoids

-glycolipids

What is the composition of fatty acids?

-varying lengths (3-30) of hydrocarbons (hydrophobic portion)

-a carboxylic group (hydrophilic portion) at one end of the chain

What are the characteristics of each fatty acid determined by?

-chain length: longer chains = more hydrophobic; higher melting points

-degree of unsaturation: influenced by number of double bonds; more double bonds lower its melting point and increases its fluidity

Myristic Acid

a saturated fatty acid

Palmitoleic Acid

a fatty acid with 1 double bond

Arachidonic Acid

a fatty acid with 4 double bonds

Cervonic Acid

-fatty acid with 6 double bonds

-present abundantly in membranes of retinal photoreceptors

-22:6

-6% in red blood cells

-10% in rod outer segments

-imparts considerable fluidity to the cell membranes and photoreceptor discs

-a PUFA is vulnerable to destruction by oxidative processes in the retina

What are carbon length and degree of unsaturation important determinants for in fatty acids?

melting point and fluidity of biological membranes

What does increasing the carbon length of a fatty acid do?

thickens the cell membrane and raises its melting point

What does inclusion of several double bonds in fatty acids do?

-lowers the melting point sufficiently

-membrane becomes fluid or flexible

-enable the fatty acids to slide freely by one another

Fatty Acids

building blocks of membrane lipids

Triacylglycerols

-represent a storage form of fatty acids

-one molecule: 3 fatty acids covalently bonded to a glycerol molecule using ester bonds

-fatty acids on each glycerol mol are mixed types of both chain lengths and saturation

-this enables the lipid to exist in liquid form

aka triglycerides

Where are most triacylglycerols kept?

in fat cells

What are triacylglycerols a source for?

-represent a large deposit of storage energy

-a source of heat insulation for humans and animals

-main source of Acetyl CoA from lipids

-significant amount of energy can be stored in triacylglycerols form (100,000 kcals) vs glycogen form (600 kcals)

What can breakdown of triacylglycerols to Acetyl CoA occur without?

ketone body formation (occurs in diabetes)

What is the amount of triacylglycerols in the eye like?

eye has a limited amount of triacylglycerols to maintain cellular membranes

Phospholipids

-most important lipid class

-required for the formation and maintenance of all forms of cellular membrane

-structure similar to triacylglycerols

-phosphate ester binds the glycerol to one of four kinds of polar groups: ethanolamine, choline, serine, and inositol

What do polar head groups of phospholipids bond to?

bond to C-3 of the glycerol molecule via a phosphate bridge

What is the fatty acid composition on C-1 and C-2 of the glycerol like compared to phospholipids?

differs in both chain and degree of saturation

Where does the polar head region of the molecule of phospholipids protrude?

into the aqueous regions inside and outside of a cell

Where do non-polar fatty acid regions of phospholipids bury themselves?

into the interior of a cell membrane

What is the structure of a cell membrane?

-2 lipid layers (bilayer): fatty acid portions face each other

-polar head groups: face the aqueous portions of each side of a cell (plasma membrane) or cell chamber (subcellular organelle)

-fatty acid composition: varies based on cell's functional needs

-rod outer segment discs

What do the rod outer segment discs of a cell membrane require?

-require a high degree of membrane fluidity for visual transduction function

-cervonic acid %: almost six times greater than that of RBC plasma membranes

Isoprenoids

-built from 5 carbon units: isoprene

-cholesterol, vitamin A, coenzyme Q

Cholesterol

-composed of 4 fused rings

-2 methyl groups

-a hydrocarbon branch and a single hydroxy group

-has 27 carbons

-highly apolar lipid

-readily fits into membrane structures where it imparts rigidity to the membrane

Why are isoprenoids important?

-a source of cholesteryl esters

-important components of the precorneal tear film

-a synthetic precursor for various steroid hormones that affect ocular function

What is the rod outer segment disc of isoprenoids like?

-fluidity: important for visual transduction

-cholesterol: makes up only 8% of the lipids of the disc membranes

Chalazion

-a granulomatous inflammation of the eyelid margins

-inflammation associated with meibomian gland lipids

-lipids are rich in cholesterol

-source of this lipid: from the membranes of inflammatory cells such as neutrophils, lymphocytes, and WBCs

Esters

bonds formed between a carboxylic acid and either an alcohol or hydroxy group attached to a ring compound

What are some examples of lipid esters?

-triacylglycerols

-phospholipids

-cholesteryl esters

Waxes

esters of long chain fatty acids and long chain alcohols

How are waxes important in the eye?

-major component of the lipid layer of the precorneal tear film

-they exist as liquids at the temperature of the tear film at around 35 degrees Celsius

Eicosanoids

-cyclic lipids derived from eicosanic acids (20 carbon) such as arachidonic acid

-egs. include prostaglandins and leukotrienes

Glycolipids

-important membrane components found in nervous, ocular, and other tissues

-lipids that contain carbohydrates such as galactose

Sphingosine

-a long chain amino alcohol

-basic structure that binds glycolipids

Ceramide

when a second fatty acid is bound as an ester to sphringosine

Sphingomyelin

phosphocholine is esterified to a ceramide

Cerebroside and Ganglioside

-a glycolipid where phosphocholine is replaced by one or more carbohydrates

-have one or more sugars attached to the ceramide portion of the glycolipid

Tay-Sachs Disease

-a metabolic storage disease

-an enzyme defect in the catabolism of glycolipids

-N-acetyl galactosamine is not removed due to a deficiency of the enzyme hexosaminidase A

-enzyme catalyzes the breakdown of ganglioside molecules as new molecules are synthesized

Cell Membrane

-functional barriers to both cell surfaces and interior compartments of cells

-also comprised of proteins and carbohydrates

What do the simplest cell membranes contain?

only lipids

What do simple lipids contain?

fatty acids - in fatty acids, lipids tend to congregate together

How does the hydrophobic bulk of cell membrane associate together?

by weak hydrophobic bonds

What do lipids form in an aqueous environment?

spherical micelles

What do phospholipids form in an aqueous environment?

lipid bilayers (basis of all cell membranes)

What are some common lipids in the cell membrane?

-phospholipids

-cholesterol

-glycolipids

What are polar groups of cell membranes like?

extend on either side towards an aqueous environment either inside or outside of the cell

What are non-polar regions of cell membranes like?

from both sides of the membrane associate hydrophobically

What are the components of cell membranes?

-phospholipids

-cholesterol

-glycolipids

-polar groups

-nonpolar regions

-variable lengths of both saturated and unsaturated fatty acids are present

-variations in polar head groups

What is the structure of the lipid bilayer of the cell membrane like?

-more PC molecules on the outer surface of the lipid bilayer

-predominance of PE molecules on the inner surface of the lipid bilayer

-phospholipids with net positive charges occur exteriorly

-presence of double bonds allow fatty acids to slide by one another easily

What are the roles of the lipid components in the cell membrane?

glycolipids serve two functions:

-part of the overall lipid bilayer structure

-contribute short chain carbohydrates (sugar arms) into the outer aqueous volume just outside the cells

-they form part of the cellular glycocalyx (sugar coat) due to their short sugar arms

What is the role of proteins in the cell membrane?

act as doors of cells

What are the two main types of membrane proteins in the cell membrane?

-intrinsic (integral)

-extrinsic (peripheral)

Intrinsic Proteins

cross or extend into the lipid bilayer of a cell membrane

Extrinsic Proteins

-are only associated with either side of the membrane

-can be isolated from membranes based on solubility

What do intrinsic proteins in the cell membrane require?

a strong detergent for separation (extrinsic proteins may be separated using aqueous salts)

What are some common functions of intrinsic proteins in the cell membrane?

-transport

-reception (e.g. of insulin)

-transduction (e.g. of light)

-attachment (to basement membrane)

Rhodopsin

-an intrinsic protein; converts light into a chemical signal

-crosses the disc membrane with 7 polypeptides

What are the passive roles of extrinsic proteins in the cell membrane?

-structural (cytoskeletal maintenance)

-anchoring (glycocalyx component)

-transduction, signaling

-local movement (myosin and actin)

Transducin

an extrinsic protein sequentially included in the light transduction process with rhodopsin

What is the carbohydrate component in cell membranes?

-make up smallest percentage

-form outer sugar covering of a cell: glycocalyx

What are the two types of carbohydrates in the cell membrane?

-glycolipids

-glycoproteins

What are the roles of carbohydrate components in the cell membrane?

-extend out of the cell as long branches; interact with surrounding aqueous environment

-biological bridges

-bonding agents

-glycolipids and glycoproteins occur on membranes of subcellular organelles

What do bonding agents in the cell membrane associate with?

associate with matrix, e.g. association of epithelial cells of cornea with Bowman's membrane

Where are carbohydrates mainly found in cell membranes?

on the extracellular surface of plasma membranes

What is the protein and lipid ratio in different membranes?

-plasma membranes: protein to lipid ratio approx. 1:1

-mitochondrial inner membranes: heavily involved in electron transport and ATP production; ratio 3:1

-myelin membrane: an insulator: ratio of 1:5

helps to gauge the role of membrane - transport, metabolism, and signal transduction

What are the three types of transport mechanisms?

-simple diffusion

-passive facilitated transport

-active facilitated transport

Simple Diffusion

-very small molecules oxygen and nitrogen readily cross the membrane

-move from higher (outside the cell) to lower concentration (inside the cell)

-e.g. movement of glucose inside the cell using the protein GLUT-1

Facilitated Transport

-limited by the ability of the protein or enzyme to perform the transport

-protein-assisted transport: usually rate limited

-subject to competition or inhibition

Active Transport

-occurs from an area of lower concentration outside the cell to an area of higher concentration inside the cell

-enzyme catalysis

Enzyme Catalysis

required for the energy to operate active transport pump

Na, K-ATPase

-involved in active facilitated transport

-transports 3 ions of Sod outside a cell and 2 ions of pot inwards by hydrolyzing one molecule of ATP

Uniport

when only a single substance is transported as with GLUT-1 and sugar uptake

Cotransport

when two substances are transported simultaneously

Symport

when substances are transported in the same direction (e.g. glucose transport in kidney tubules)

Antiport

substances are transported in opposite direction (e.g. Sod, pot ATPase)

When is the precorneal tear film formed?

formed when tears are spread across cornea after eyelid blinking

What are the three parts of the precorneal layer?

-anterior or superficial lipid layer

-central aqueous layer

-posterior mucus layer

What is the total thickness of the precorneal tear film?

range from 4-40 micorometers, the latest estimate is 3 micrometers

What does the mucin layer of the precorneal tear film extend into?

the aqueous layer, hence understanding of thickness of the tear film is vague

Lipid Layer of Precorneal Tear Film

-a large variety of waxes and cholesteryl esters

-stabilizes the film (15-40 sec) during its contact time

-following stabilization, tear film breaks and stimulates the next blink = tear-film breakup time

Mucus Layer of Precorneal Tear Film

mucoid proteins

Aqueous Layer of Precorneal Tear Film

-dissolved salts and proteins

-contains lysozyme (antibacterial protein)

Tear Film

a protective layer, optically uniform

What is the composition of the lipid layer of the precorneal tear film?

-fatty acids and their alcohol derivatives

-cholesterol make up the waxes and cholesteryl esters

-more than 25% of lipid types, not completely characterized

Meibomian Gland Secretion

-69 different fatty acids

-40 fatty acid alcohols

-11 hydroxy fatty acids

What are the roles of esters in the tear film?

-help lipids to flow from their ducts to the eyelid edges

-form a film over the aqueous layer and maintain contact with it

-adhere to the eyelid skin and act as a barrier to the aqueous layer

-from a water-tight seal when the lids are closed

What can alter the ester mixture in lipids and bring about tear film abnormalities?

pathological conditions

Meibomian Gland Dysfunction

-excessive production of keratin in the ductal epithelium

-this can alter the composition of the tear film lipids

-steryl esters are decreased, cholesterol is increased and ceramides appear

-epithelial cells detach from the gland and block the flow of new lipids to their tear film

-there could be bacterial infection in the area of blocked lipids

S. Aureus

along with other bacteria, produce a cholesteryl esterase and a fatty wax esterase that hydrolize the meibomian lipids - causes meibomian gland dysfunction

Lipids of the Retina

-an important role in the phototransduction process

-the percent of fatty acids in both retina and photoreceptor membranes resemble each other

-a high concentration of the highly unsaturated cervonic acid (22:6)

What are the contents of phospholipids in photoreceptors?

have less sphingomyelin and phosphotidyl inositol than that found in nervous tissue

What is the lipid content like in outer segments of rods and cones?

-lipid content is high, presence of discs

-rods outer segment: 15% as compared to 1% of most cells

What does the high fluidity of the discs of rods allow?

allows rotational and lateral movements of rhodopsin needed for phototransduction

What helps absorb free radicals in the lipids of the retina?

presence of sufficient concentrations of Vitamin E - in the absence of Vitamin E, free radicals attack the double bonds of membrane fatty acids and break them up into fragmentary aldehydes