nutr 455 exam 3

Simple Lipids

lipids that yield two products

Fatty acids
Sterols
Mono,di,triacylglycerol

Complex Lipids

lipids that yield three or more products

Phospholipids
Glycolipids
Lipoproteins

How are lipids classified?

1. Based on the products generated from hydrolysis

• Simple lipids (yield 2 types of products): Fatty acids

• Complex Lipids (yield 3 or more products): Phospholipid

2. Based on the products of synthesis

• Fatty acids and their derivatives

• Sterols and their derivatives

What are the nutritionally important lipids

Fatty acids

Triacylglycerol, diacylglycerol, monoacylglycerol

Phospholipid

Sphingolipids

Sterol (cholesterol, bile acids, and phytosterols)

Fatty acids are composed of:

1. Hydrocarbon chain

2. Methyl group (non-polar hydrophobic)

3. Carboxylic group (polar hydrophilic)

Fatty acids

simplest form of lipids

exist alone (free fatty acid) or as components of more complex lipids

provide most of the calories derived from dietary fat

What are the two ends of a fatty acid?

Methyl end (Omega end)

Carboxylic acid end (Alpha end)

Hydrophobic lipids

repel water

insoluble in water

lipophilic

soluble in organic solvents (ether, chloroform, acetone)

Short chain fatty acids

less than 6 carbons

Medium chain fatty acids

6-10 carbons

Long chain fatty acids

12 or more carbons

18 carbons is most common in nature

Mono-unsaturated fatty acids

Contain 1 double bond

liquid at room temperature

Foods enriched in mono-unsaturated fatty acids

Olive oil
peanut oil
canola oil

Poly-unsaturated fatty acids

Contain 2 or more double bonds

liquid at room temperature

Foods enriched in poly-unsaturated fatty acids

corn oil
sunflower oil
fish oils
nuts and seeds

Unsaturated fatty acids are \______________ at room temperature

liquid

Saturated fatty acids

No double bonds

solid at room temperature

Foods enriched in saturated fatty acids

Animal fats
Palm oil
Palm kernel oil
Coconut oil

Trans fatty acids

Fatty acids with hydrogens on opposite sides of the double bond

linear

commonly commercial products

Cis fatty acids

Fatty acids with hydrogens on the same side of the double bond

U-shaped

naturally occurring

Stearic acid

saturated fatty acid; no double bonds

Elaidic acid

a trans unsaturated fatty acid and a major trans fat found in partially hydrogenated vegetable oils

monounsaturated - contains one double bond

Oleic acid

a cis unsaturated fatty acid

comprises up to 80% of olive oil

monounsaturated - contains one double bond

The two methods of fatty acid nomenclature are:

1. Delta (∆) Nomenclature

2. Omega Nomenclature

Delta nomenclature method

INDICATE:

1. # of carbons in the fatty acid chain

2. # of double bonds

3. position of double bonds from α end (-COOH end)

Omega nomenclature method

INDICATE:

1. # of carbons in fatty acid chain

2. # of double bonds

3. position of double bonds from 𝜔 end (-CH3 end)

The delta nomenclature system and omega nomenclature system differences

delta nomenclature includes the location of all of the double bonds (ex: 18:2∆9,12)

omega nomenclature only includes the first double bond

Double bonds in fatty acids are always

separated by 3 carbons

four important naturally occurring fatty acids

palmitic acid
stearic acid
oleic acid
linoleic acid

account for 90% of the fatty acids in the average US diet

Most fatty acids have an \__________ number of carbons

even

Docosahexaenoic acid (DHA)

C22: 6∆4,7,10,13,16,19

C22:6n3

Eicosapentaenoic acid (EPA)

C20: 5 ∆5,8,11,14,17

C20:5n3

Arachidonic acid (AA)

C20: 4 ∆5,8,11,14

C20:4n6

Essential fatty acids

Fatty acids that can't be produced in the body and must be obtained from the diet.

Linoleic and alpha-linolenic acid.

Essential because the body doesn't have a desaturase enzyme for any carbon past delta C9

Linoleic acid

C18:2n6

alpha-Linolenic acid

C18:3n3

Lack of essential fatty acids can lead to:

Growth retardation
Skin disorders (dermatitis)
Kidney lesions
Early death

omega-6 (n-6) fatty acids are \________ in the diet while omega-3 (n-3) fatty acids are \________ in the diet

high, low

Linoleic acid is \___________________________

pro-inflammatory

alpha-Linolenic acid is \________________________________ and is a minor component of \__________________

anti-inflammatory

tissues

alpha-Linolenic acid is broken down into

EPA and DHA

EPA is a minor component of \__________________ and is found in \_____________________

tissues

fish and shellfish

DHA is a major component of:

DHA can be found in:

membrane phospholipids in retinal photoreceptors, cerebral grey matter, testes, and sperm

fish and shellfish

alpha-Linolenic acid can be found in:

flaxseed oil

Triacylglycerol

Represent a highly concentrated form of stored energy

Accounts for nearly 95% of dietary fat

Exist as fats (solid) or oils (liquid) depending on the fatty acids

Triacylglycerol is composed of:

glycerol backbone + three fatty acids

fatty acids are linked to glycerol through an ester bond

fatty acids are present on alternating sides of the glycerol backbone

Functions of triacylglycerols

Storage form of energy (adipose tissue)
Energy (9 kcal/g)
Supply essential fatty acids
Carry fat soluble compounds
Cell signaling and gene expression
Taste and texture

diacylglycerol (DAG) is composed of:

glycerol backbone + two fatty acids

monoacylglycerol is composed of:

glycerol backbone + one fatty acid

Triacylglycerol lipase

Cleaves a fatty acid off of TAG

Diacylglycerol lipase

Cleaves a fatty acid off of DAG

Monoacylglycerol lipase

Cleaves the fatty acid off of MAG

Importance of DAG and MAG

both are intermediates in some metabolic reactions

Phospholipids

a lipid consisting of a glycerol bound to two fatty acids and a phosphate group

amphipathic

Functions of phospholipids

form bilayers of cell and organelle membranes

are surface components of lipoproteins

mediate cell signaling

emulsify food to keep fat and water mixed

Amphipathic

A molecule that has both a hydrophilic region and a hydrophobic region.

Phosphatidic acid

a compound in which two fatty acids and phosphoric acid are esterified to the three hydroxyl groups of glycerol

(without a head group)

Common head groups of phospholipids:

Choline, inositol, serine, and ethanolamine

Phosphatidyl choline

most common, makes up 50% of the phospholipids in cell membranes

Phosphatidyl ethanolamine

Second regarding abundance

Phosphatidyl serine

Cell membrane phospholipid.

Attracts phagocytes during apoptosis

Phosphatidyl inositol

Cell membrane phospholipid

Anchors membrane proteins by covalently attaching to the proteins

Intracellular signaling

What is the result of hydrolysis of phosphatidylinositol?

Phosphatidylinositol in the plasma membrane can be doubly phosphorylated by ATP forming Phosphatidylinositol-4,5-bisphosphate

stimulation by insulin --\> inositol-1,4,5-trisphosphate and diacylglycerol

Inositol-1,4,5-trisphosphate causes the release of Ca2+ (second messenger) --\> enzyme activation or other hormonal responses

diacylglycerol activates protein kinase C --\> enzyme activation

Sphingolipids

a compound that consists of a fatty acid and a sphingosine

found in high concentrations in the brain and other tissues of the nervous system, especially membranes

Has 18-carbon amino alcohol sphingosine as a backbone

All have a fatty acid attached to the amino group

What is the name of the sphingolipid with no head group?

ceramide

R1 \= fatty acid
R2 \= H

What are the common sphingolipid head groups?

phosphocholine
galactose
glucose
oligosaccharide

Sphingomyelin

R1 \= fatty acid
R2 \= phosphocoline

abundant in myelin sheath of nerve tissues

Cerebroside

R1 \= fatty acid
R2 \= galactose/glucose

Galactocerebrosides: abundant in myelin sheath of nerve tissues

Glucocerebrosides: mainly in spleen and red blood cells

Gangloside

R1\= fatty acid
R2 \= oligosaccharide

Mainly in nerve system, markers in cellular recognition or receptors for hormones and toxins

Sterols

Unique structure: have a four-ring steroid nucleus and at least one hydroxyl group

What are the three nutritionally important sterols?

Cholesterol

Phytosterols

Cholesterol

Most common sterol in humans

Exists in free form, or esterified with a fatty acid

Important constituent of the plasma membrane

Precursor for many steroids (Vitamin D, Sex hormones, corticosteroid hormones, Bile acids)

Cholesterol is a precursor for the formation of bile acids. What is the function of bile acids?

Bile has an affinity for both fat and water, so it can bring the fat into the water.

Bile's emulsifying action converts large fat globules into small droplets that repel each other.

After emulsification, more fat is exposed to the enzymes, making fat digestion more efficient.

cholic acid and chenodeoxycholic acid

primary bile acids

Phytosterols

Component of plant cell membranes

Structurally similar to cholesterol

Minimally absorbed

Reduce cholesterol absorption (it is not understood why, but the beneficial effect is well established)

How are phytosterols structurally different from cholesterol?

The side chains differ

Our body is able to recognize the difference in the side chains, so phytosterols are only minimally absorbed

What are some common phytosterols?

sitosterol
campesterol
stigamsterol

What is the health benefit of dietary intake of phytosterols?

Intakes of 2-3 g/day of phytosterol were shown to decrease plasma LDL-Cholesterol by 10%.

The Western diet includes what types of lipids?

triacylglycerols
phospholipids
cholesterol

\_____________________ are the major contributor of lipids in our diet

triacylglycerols

Triacylglycerol digestion

Lingual and gastric lipases start to digest lipids in stomach

Pancreatic lipase digests lipids in small intestine

Lingual and gastric lipases

Lingual lipase - produced by salivary glands

Gastric lipase - produced in the stomach

digest mainly medium and short chain fatty acids

hydrolyze fatty acids at the sn-3 position

products: 1,2-diacylglycerols, one fatty acid

Pancreatic lipase

digests all fatty acids including long chain fatty acids

hydrolyze fatty acids primarily at sn-1 and secondarily at sn-3

products: 2-monoacylglycerols, free fatty acids

Orlistat

anti-obesity drug, a derivative from Streptomyces toxytricini. (Has many gastrointestinal side effects)

two drugs commonly used are xenical (Roche) and alli (GSK)

Inhibits fatty acid absorption by binding to pancreatic lipase and not allowing it to break down fatty acids for digestion

Pancreatic Phospholipase A2

Cleaves phospholipids to lysophospholipids

pancreatic cholesterol esterase

Cleaves cholesterol esters

How does triacylglycerol, cholesterol, cholesterol ester, and phospholipid enter the stomach?

largely intact

Only \_____________________ are acted upon in the stomach

triacylglycercols

Micelles contain:

the final digestion products from lipid hydrolysis including: free long-chain fatty acids, 2-monoacylglycerols, free cholesterol, phytosterols, lysophospholipids, fat-soluble vitamins

Micelle function:

small enough to interact with brush border and move the lipid content into enterocytes

Two mechanisms of fatty acid, monoacylglycerol and lysophospholipid absorption

Passive diffusion:
occurs when lipid concentration in lumen is higher than that of cells
Amphiphathic nature of micelles and membrane lipids


Protein transporter-dependent absorption:
CD36: fatty acids, monoacylglycerol (not sure for lysophospholipid)

Cholesterol Absorption

There is no oxidative pathway for cholesterol in humans, fecal excretion is the primary catabolic route for cholesterol homeostasis

Uptake of cholesterol by enterocytes

cholesterol must incorporate in micelles

uptake by the cell is mediated by a brush border protein called NPC1L1

NPC1L1

Key transporter involved in cholesterol absorption

Allows cholesterol/phytosterol to be absorbed into enterocyte

Ezetimibe

inhibits the function of NPC1L1 - decreases cholesterol absorption

ACAT2:

catalyzes cholesterol esterification

MTP:

catalyzes assembly of lipid-protein complex

Apo-B48:

surface protein of lipid-protein complex

ABCG5 and ABCG8

transport cholesterol/phytosterol out of the enterocyte

50% of cholesterol is transported out

100% of phytosterol is transported out