7-26 Lipids

a phosphodiester bond joins the head group to glycerol the phosphate group can bear a negative, neutral, or positive charge can be any of a wide variety in general, glycerophospholipids contain: a C16 or C18 saturated fatty acid at C-1 a C18 or C20 unsaturated fatty acid at C-2

1. Be able to describe the general features of phospholipid structure.

Phospholipid degradation... phospholipases of the A type remove one of the two fatty acids lysophospholipases remove the remaining fatty acid lysosomal enzymes catalyze the stepwise removal of sugar units of gangliosides phospholipase C hydrolyzes PIP2 to IP3 and diacylglycerol (intracellular messengers)

1. Describe the process of phospholipid degradation.

- class of membrane phospholipids and glycolipids - have a polar head group and two nonpolar tails - contain no glycerol - contain one molecule of the long-chain amino alcohol sphingosine or one of its derivatives

1. Describe the structural features and role of sphingolipids.

Prostaglandins (PG)

= class of eicosanoids that contain a five-carbon ring array of functions: stimulate contraction of the smooth muscle of the uterus affect blood flow to specific organs, the wake-sleep cycle, and the responsiveness of certain tissues to hormones elevate body temperature and cause inflammation and pain

Leukotrienes (LT)

= class of eicosanoids that contain three conjugated double bonds powerful biological signals leukotriene D4 induces contraction of the smooth muscle lining the airways to the lung

Thromboxanes (TX) platelets

= class of eicosanoids that have a six-membered ring containing an ether produced by ____ (also called thrombocytes) act in the formation of blood clots and reduction of blood flow to the site of a clot

sterols

= compounds characterized by a rigid system of four fused hydrocarbon rings

glycolipids

= contain a simple sugar or a complex oligosaccharide at the polar ends

omega-3 (ω-3) fatty acids

= double bond between C-3 and C-4 relative to the most distant carbon (ω)

omega-6 (ω-6) fatty acids

= double bond between C-6 and C-7 relative to ω

Lipases adipocytes and germinating seeds

= enzymes that catalyze the hydrolysis of stored triacylglycerols, releasing fatty acids for export to sites where they are required as fuel ____ and _______ ____ contain lipases

Globosides

= glycosphingolipids with 2 or more sugars, usually D-glucose, D-galactose, or N-acetyl-D-galactosamine

Cerebrosides galactose glucose

= have a single sugar linked to ceramide those with galactose are found in the plasma membranes of cells in neural tissue those with _____ are found in the plasma membranes of cells in nonneural tissues

phospholipids

= have hydrophobic regions composed of two fatty acids joined to glycerol or sphingosine

archaeal tetraether lipids

= have two very long alkyl chains ether-linked to glycerol at both ends

Cholesterol

= major sterol in animal tissues amphipathic polar head group nonpolar hydrocarbon body membrane constituents

Sphingomyelins phosphocholine phosphoethanolamine

= subclass of sphingolipids that contains _________ or ___________ as their polar head group

Biological lipids

A diverse class of organic molecules that share the common feature of insolubility in water

neutral glycolipids

Cerebrosides and Globosides sometimes called ____ _____, as they have no charge at pH 7

structure and composition

Chemical Properties of Lipids The chemical properties of lipids are related to their ____ and _____.

Arachidonic Acid

Eicosanoids Are Derived From _____ ____

exergonic

Fats and Oils Used as Stored Energy Are Derivatives of Fatty Acids •fatty acids = hydrocarbon derivatives • •oxidation of fatty acids (to CO2 and H2O) is highly ______ (energy producing)

carboxylic acids hydrocarbon tails 4 to 36

Fatty Acids Are Hydrocarbon Derivatives fatty acids = ______ acids with _____ ___ ranging from ___ to ___ carbons long can be saturated or unsaturated can be branched or unbranched

COO-- hydrated

Fatty acids structure Water-insoluble hydrocarbons with attached to _____ used for cellular energy storage Generally highly reduced and thus provide a rich source of stored chemical energy Storage of hydrophobic fats (fatty acids) as triacylglycerols is not ______; highly efficient because water is not needed to hydrate the stored fats

beta-estradiol

Female sex HN produced in the ovaries and placenta

1. Phospholipids (glycerophospholipids and sphingolipids) 2. Glycolipids (shingolipids and galactolipids) 3. Sterols 4. Archaeal tetraether lipids

Identify three types of membrane lipids

Sandhoff Disease

In ____ disease, Hexosaminidase A and B are in defect (they remove GalNAc from globoside)

Fabry Disease

In _____ disease, alpha-galactosidase A (removes Gal) is in defect

Biological

Lipids: Features and Functions.... ________ lipids: •Chemically diverse •Generally insoluble in water. Lipids functions are also diverse: •Stored energy Components of biological membrane Other lipid functions: •electron carriers •***hydrophobic anchors for proteins •emulsifying agents in the digestive tract •hormones •intracellular messengers

To obtain energy from fat, triglycerides must first be broken down by hydrolysis into their two principal components, fatty acids and glycerol. This process, called lipolysis, takes place in the cytoplasm. The resulting fatty acids are oxidized by β-oxidation into acetyl CoA, which is used by the Krebs cycle. The glycerol that is released from triglycerides after lipolysis directly enters the glycolysis pathway as DHAP. Because one triglyceride molecule yields three fatty acid molecules with as much as 16 or more carbons in each one, fat molecules yield more energy than carbohydrates and are an important source of energy for the human body. Triglycerides yield more than twice the energy per unit mass when compared to carbohydrates and proteins. Therefore, when glucose levels are low, triglycerides can be converted into acetyl CoA molecules and used to generate ATP through aerobic respiration.

Lipolysis

Testosterone

Male sex HN produced in the testes

cellular messengers, hormones, electron carriers, or pigments

Many lipids are present in the cell at smaller amounts than those making up membranes or being stored as fat. These lipids can function as (HEPC) 1. 2. 3. 4.

Ceramide and spingomyelin

Membrane Sphingolipids Serve As Sources of Intracellular Messengers ____ and ____- are potent regulators of protein kinases ceramide or its derivatives are involved in the regulation of: cell division differentiation migration programmed cell death

glycerophospholipids and sterols signaling processes and molecular recognition

Membrane lipids .... composed of hydrophobic tails attached to polar head groups cellular membranes are composed of a variety of lipids, including _____ and _____ membrane lipids participate in _____ ____ and ___ ___.

ganglioside GM2 hexosaminidase A

More common is Tay-Sachs disease, in which _______ accumulates in the brain and spleen (Fig. 2) owing to lack of the enzyme ________ are progressive developmental retardation, paralysis, blindness, and death by the age of 3 or 4 years

1. Fats and oils 2. Waxes 3. Phospholipids 4. Steroids

Name four major categories of biological lipids

1. Fats and oils 2. Waxes 3. Phospholipids 4. Steroids

Name four major categories of biological lipids.

- Overall: F.as are Water-insoluble hydrocarbons with attached to COO--used for cellular energy storage 1. Highly reduced: provides rich source of stored chemical energy 2. Storage of hydrophobic fats (fatty acids) as triacylglycerols is not hydrated: highly efficient b/c water is not needed to hydrate the stored fats NOTE: F.as = = carboxylic acids with hydrocarbon tails ranging from 4 to 36 carbons long (C4 to C36) can be saturated or unsaturated can be branched or unbranched

Name two chemical properties of long chain fatty acids and describe how these properties contribute to fatty acid function.

Nomenclature for Unbranched Fatty Acids

Nomenclature for Unbranched Fatty Acids the chain length and number of bonds, separated by a colon numbering begins at the carboxyl carbon positions of double bonds are indicated by ∆ and a superscript number

omega-3 PUFA α-linolenic acid (ALA; 18:3(∆9,12,15))

PUFAs and Human Nutrition humans must obtain the ________ from their diet

structure and metabolism

Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular Signals phosphatidylinositol (PI) and its phosphorylated derivatives regulate cell ______ and _____

A lysophospholipases lysosomal enzymes

Phospholipids and Sphingolipids Are Degraded in Lysosomes Phospholipid degradation... phospholipases of the ___ type remove one of the two fatty acids _______ remove the remaining fatty acid ____ ___ catalyze the stepwise removal of sugar units of gangliosides

...

TBL 1 Objectives

...

TBL Objectives 2

saturated unsaturated

The Fatty Acids in Glycerophospholipids can be any of a wide variety in general, glycerophospholipids contain: a C16 or C18 ______ fatty acid at C-1 a C18 or C20 ______ fatty acid at C-2

three fatty acids glycerol

Triacylglycerols Are Fatty Acid Esters of Glycerol ______- composed of _____ _____ ___ in ester linkage with a single ______ May consist of (one kind of fatty acid) mixed (two or three different fatty acids) non-polar, hydrophobic

lipid droplets Adipocytes (fat cells)

Triacylglycerols Provide Stored Energy and Insulation vertebrates store triacylglycerols as ___ ____ in _______ (___ cells) plants store triacylglycerols in the seeds

calcitrol

Vitamin D3 Production and Metabolism ______ = hormone that regulates calcium uptake in the intestine and calcium levels in the kidney and bone

....

Waxes are esters of long-chain fatty acids and long-chain alcohols. There are three subclasses of sphingolipids, all derivatives of ceramide but differing in their head groups: sphingomyelins, neutral (uncharged) glycolipids, and gangliosides.

Fatty acids energy storage triacylglycerols

___ ____ = water-insoluble hydrocarbons used for cellular ___ ___. highly reduced and thus provide a rich source of stored chemical energy for cells. Storage of hydrophobic fats as _______ is also highly efficient because water is not needed to hydrate the stored fats

Platelet-Activating Factor basophils serotonin

____ ____= an ether lipid that serves as a potent molecular signal releases from leukocytes called ______ stimulates platelet aggregation and ______ release plays a role in inflammation and the allergic response

Niemann-Pick sphingomyelinase

_____-____ disease is caused by a rare genetic defect in the enzyme ________, the enzyme that cleaves phosphocholine from sphingomyelin. Sphingomyelin accumulates in the brain, spleen, and liver. The disease becomes evident in infants and causes mental retardation and early death.

Sterols

_____Have Four Fused Carbon Rings - structural lipids present in the membranes of most eukaryotic cells steroid nucleus: consists of four fused rings almost planar relatively rigid

Sphingolipids (Are Derivatives of Sphingosine) sphingosine

______ = = class of membrane phospholipids and glycolipids have a polar head group and two nonpolar tails contain no glycerol contain one molecule of the long-chain amino alcohol ______ or one of its derivatives

Polyunsaturated Fatty Acids (PUFAs)

______ = = contain more than one double bond in their backbone

Eicosanoids

______ Carry Messages to Nearby Cells = paracrine hormones, substances that act only on cells near the point of synthesis instead of being transported in the blood involved in: reproductive function inflammation, fever, and pain associated with injury or disease formation of blood clots regulation of blood pressure gastric acid secretion

Sphingolipids neurons

______ at Cell Surfaces Are Sites of Biological Recognition prominent in the plasma membranes of _____ human blood groups (O, A, B) are determined in part by the oligosaccharide head groups of these glycosphingolipids

Vitamin D3 (cholecalciferol)

________ = formed in the skin from 7-dehydrocholesterol in a photochemical reaction driven by the UV component of sunlight not biologically active converted by enzymes in the liver and kidney to calcitriol

Membrane lipids glycerophospholipids and sterols

composed of hydrophobic tails attached to polar head groups. Cellular membranes are composed of a variety of lipids, including _______ and _____. These lipids are used for structuring membranes as well as for displaying molecules on the membrane surfaces for signaling and molecular recognition

Trans Fatty Acids ("Trans Fats") cardiovascular

dietary intake of ______ fatty acids is linked to a higher incidence of ________ disease

prostaglandins, thromboxanes, leukotrienes lipoxins

four major classes of eicosanoids = 1. 2. 3. 4.

Brassinolide

growth regulator found in vascular plants

Glycosphingolipids

have head groups consist of one or more sugars connected directly to the -OH at C-1 of the ceramide moiety do not contain phosphate occur largely in the outer face of plasma membranes

eicosapentaenoic acid (EPA; 20:5(∆5,8,11,14,17)) docosahexaenoic acid (DHA; 22:6(∆4,7,10,13,16,19))

humans use ALA to synthesize: 1. 2.

Phosphatidylinositol 4,5-Bisphosphate (PIP2) phospholipase C

in the cytoplasmic face of plasma membranes serves as a reservoir of messenger molecules that are released in response to extracellular signals _________ __- hydrolyzes PIP2 to IP3 and diacylglycerol (intracellular messengers)

Gaucher Disease

in_____ disease, glucocerebrosidase is in defect (removes Glucose from ceramide) is defected

Gangliosides

oligosaccharides as their polar head groups and 1 or more residues of N-acetylneuraminic acid (Neu5Ac), a sialic acid, at the termini 1 sialic acid residue = GM (M for mono-) series 2 sialic acid residues = GD (D for di-) series 3 sialic acid residues = GT (T for tri-) series (and so on)

Prednisone

synthetic steroid used as an anti-inflammatory agent

1:1 4:1

the optimal dietary ratio of omega-6 to omega-3 PUFAs is between ___ and ___

triacylglycerols LDL (low-density lipoprotein) HDL Inflammatory

trans fatty acids does...: 1. raise the level of _______ in the blood 2. raise the level of _____ ("bad") cholesterol in the blood 3. lower the level of ____ ("good") cholesterol 4. increase the body's _______ response

Structural role: - amphipathic polar head group nonpolar hydrocarbon body membrane constituents ROLE Sterols Serve as Precursors for Products with Specific Biological Activities steroid hormones regulate gene expression bile acids = polar derivatives of cholesterol that emulsify dietary fats in the intestine to make them more readily accessible to digestive lipases

1. Describe the structural role and role of sterols

- Ether linked alkene for one of them, double bond b/t C1 and C2 - Ethanolamine as part of polar head group

1. Distinguish the structure of plasmologens from other phospholipids.

Structure: composed of three fatty acids in ester linkage with a single glycerol Nonpolar, hydrophobic Function: provide energy storage and insulation - vertebrates store triacylglycerols as lipid droplets in adipocytes (fat cells) - plants store triacylglycerols in the seeds

1. Draw the general structure of triacylglycerols and identify their functions.

- Include: Glycerophospholipids and sterols - Structure: Hydrophobic tail attached to polar head groups - Role: Structure membranes, display molecules on membrane surfaces for signaling and molecular recognition

1. Identify general properties of membrane lipids

- Hormones - Electron carriers - Pigments - Cellular messengers

1. Name four general functions of lipids.

Glycerophospholipids Are Named as Derivatives of Phosphatidic Acid - NOTE: saturated f.a bond to C1 and unsaturated on C2 usually - Parent derivative of phospholipids - Net charge at pH 7 = -2 - -X = -H

1. Understand the contribution of phosphatidic acidic in the structure of phospholipids.

paracrine hormones, substances that act only on cells near the point of synthesis instead of being transported in the blood involved in: reproductive function inflammation, fever, and pain associated with injury or disease formation of blood clots regulation of blood pressure gastric acid secretion

1. Understand the definition of eicosanoids

Lipoxins (LX)

= class of eicosanoids that are linear and contain several hydroxyl groups along the chain potent anti-inflammatory agents

lysosomes

Abnormal Accumalations of Membrane Lipids: Some inherited Human diseases The polar lipids of membranes undergo constant metabolic turnover, the rate of their synthesis normally counterbalanced by the rate of breakdown. The breakdown of lipids is promoted by hydrolytic enzymes in ______, each enzyme capable of hydrolyzing a specific bond. When sphingolipid degradation is impaired by a defect in one of these enzymes (Fig. 1), partial breakdown products accumulate in the tissues, causing serious disease.

gangliosides

Abnormal Accumulations of Membrane Lipids genetic defects in any of these hydrolytic enzymes leads to the accumulation of _______ in the cell

reduced unhydrated

Advantages to Using Triacylglycerols as Stored Fuels two significant advantages: Generally highly or more _____ state Stored in ______ form

the chain length and number of bonds, separated by a colon numbering begins at the carboxyl carbon positions of double bonds are indicated by ∆ and a superscript number

Be able to utilize fatty acid nomenclature

water

Biological Membranes double layer of lipids that acts as a barrier to polar molecules and ions membrane lipids amphipathic hydrophobic regions associate with each other hydrophilic regions associate with _____

ceramide

C-1, C-2, and C-3 of sphingosine are structurally analogous of the three carbons of glycerol in glycerophospholipids _______ = compound resulting when a fatty acid is attached in amide linkage to the -NH2 on C-2 structurally similar to a diacylglycerol

even 9;10 12;15 cis

Common Patterns in Fatty Acids ____ numbers of carbon atoms (12 to 24 carbons) mostly straight chains Can be unsaturated if monounsaturated, the double bond is usually between C-__ and C-__ (∆9) if polyunsaturated fatty acids: the double bonds are usually ∆___ and ∆___ double bonds are usually separated by a methylene group double bonds are usually in the ___ configuration

1. Phospholipids 2. Glycolipids 3. Archaeal tetraether lipids 4. Sterols

Four General Types of Membrane Lipids (GAPS)

chorionic villus sampling amniocentesis

Genetic counseling can predict and avert many inheritable diseases. Tests on prospective parents can detect abnormal enzymes, then DNA testing can determine the exact nature of the defect and the risk it poses for offspring. Once a pregnancy occurs, fetal cells obtained by sampling a part of the placenta (_________) or the fluid surrounding the fetus (_______) can be tested in the same way.

glycerophospholipids (phospholipids or phosphoglycerides)

Glycerophospholipids Are Derivatives of Phosphatidic Acid two fatty acids are attached in ester linkage to the first and second carbons of glycerol a highly polar or charged group is attached through a phosphodiester linkage to the third carbon

Phosphatidic phosphodiester

Glycerophospholipids Are Named as Derivatives of _______- Acid a ______ bond joins the head group to glycerol the phosphate group can bear a negative, neutral, or positive charge

Cortisol

HN produced in the adrenal cortex; regulates glucose metabolism

Aldosterone

HN produced in the adrenal cortex; regulates salt excretion

increased decreased

Solubility of Fatty Acids poor solubility in water due to the nonpolar hydrocarbon chain - (increased or decreased) chain length decreases solubility - (increased or decreased) double bond number decreases solubility carboxylic acid group is polar and ionized at neutral pH

ether lipids plasmalogens

Some Glycerophospholipids Have Ether-Linked Fatty Acids ____ ____ = one of the two acyl chains is attached to glycerol in ether - chain may be saturated chain may contain a double bond between C-1 and C-2 as in ________ plasmalogens

Steroids D

Steroid Hormones Carry Messages between Tissues _____= oxidized derivates of sterols - lack the alkyl chain attached to ring ___ of cholesterol - more polar than cholesterol steroid hormones move through the bloodstream (on protein carriers) to target tissues binding to highly specific receptor proteins in the nucleus triggers changes in gene expression

...

Steroids Derived From Cholesterol

bile acids

Sterols Serve as Precursors for Products with Specific Biological Activities steroid hormones regulate gene expression ____ ____ = polar derivatives of cholesterol that emulsify dietary fats in the intestine to make them more readily accessible to digestive lipases