lipids

structure and classes

Introduction to Lipids

• Polymers comprised of fatty acids (lipid monomer)

• Water-insoluble molecules with a general formula of R-COOH

  • Soluble in nonpolar organic solvents like hexane and turpentine

• May be attached to carbohydrates (glycolipids) or proteins (proteolipids)

• Unlike the other biomolecules, lipids are NOT considered to be true polymers

  • Why?

Why Aren’t Lipids True Polymers?

• Large biomolecule?

  • No

• Many monomers?

  • No

• Monomers interlinked?

  • No

The Role of Lipids

• Have a variety of important biochemical roles:

  • Form membranes as barriers

  • Serve as a stored fuel (energy) source

  • Are involved in signal transduction pathways

Lipids Can Have a Dual Chemical Nature

• Lipids have both hydrophilic and hydrophobic parts (amphipathic)

• Their fatty acid monomers also have this dual chemical nature

Fatty Acids: Saturated and Unsaturated

• Fatty acids may be saturated or unsaturated

  • Saturated = composed of carbon-carbon single bonds

  • Unsaturated = one or more carbon-carbon double or triple bonds

• May also be monounsaturated or polyunsaturated

• Naturally-occuring fatty acids with carbon-carbon triple bonds are rare

• Can have unsaturated cis and trans fat

Saturated or Unsaturated? Mono or poly?

Fatty Acid Nomenclature

• Fatty acids have common and systematic names

• Common name may be reference to what fatty acid is isolated from

  • Palmitate from palm oil (systematic name: n-hexadecanoate*)

• Systematic name derived from parent hydrocarbon

  • Indicates # carbon atoms, single vs. double or triple bonds, etc.

  • Follows IUPAC conventions

FA Nomenclature by Numbers

• Composition and structure can also be designated by numbers (X:X)

• Numbering begins with carboxyl terminus; ends with w (omega) carbon

• Fatty acid below is 18:3 → 18 total carbons, 3 carbon-carbon double bonds

• If want to stipulate where double bonds are in monomer, use delta symbol

  • Example: 18:3^delta9,12,15

Understanding Omega Fatty Acids

• Does w refer to omega fatty acids?

  • Yes

• Omega-3 and omega-6 refer to location of first carbon-carbon double bond, if you start counting from the w carbon

• Synthesis requires a transmembrane desaturase

  • Enzyme introduces a double bond in a particular location (like delta9)

  • Humans lack w³ and w⁶ desaturases

    • This is why we need to consume w³ and w⁶ fatty acids

Omega-3 or Omega-6?

• Notice both examples are polyunsaturated fatty acids (PUFAs)

Fatty Acids Vary in Chain Length and Unsaturation

• Usually contain an even number of carbon atoms – 16 and 18 common

• When double bonds are present, generally in cis configuration

  • So what are trans fats?

• Carbon # and bond configuration consequence of fatty acid synthesis

• Degree of unsaturation = number of carbon-carbon double bonds within a fatty acid

• Looking at the graph, what do you notice?

• Melting point = temperature when compound containing fatty acid transitions from solid to liquid

Four Classes of Lipids

• Triacylglycerols

• Phospholipids

• Glycolipids

• Steroids

• Containing fatty acids: triacylglycerols, phospholipids, glycolipids

• Involved with membranes: phospholipids, glycolipids, steroids

Triacylglycerols (TAGs)

• General structure: 3 fatty acids attached to glycerol

• Fuel source stored within adipocytes in mammalian adipose tissue

  • Cells specialized for TAG synthesis, storage and mobilization

  • Form large fat globules within the cytoplasm

  • Adipose tissue functions as insulation as low thermal conductivity

• Since nonpolar, stored in bulk without water

  • Differs from glycogen (a carbohydrate), which is stored in hydrated form in humans

Phospholipids

• General structure: 1 or 2 fatty acids attached to a platform (either glycerol or sphingosine)

  • Also contain an alcohol and a phosphate

• If glycerol, then a phosphoglyceride; if sphingosine, then a sphingolipid

• Polar head is negatively-charged, while nonpolar tails are uncharged

• Form biological membranes (plasma and organelle) that serve as barriers

  • Exhibit polymorphism (assemble into a variety of stable morphologies; Greek for “many shaped”) which facilitates membrane stability and lipid:protein interactions

Revisiting Cardiolipin (CL)

• Phosphoglyceride with 2 phosphate headgroups, 3 glycerols, and 4 fatty acids

  • Abundant within inner mitochondrial membrane (15-20% of lipids)

  • Helps stabilize cristae, as abnormal CL disrupts cristae morphology

• Generally fatty acids are highly diversified (i.e., differ in length and saturation)

  • Exception: mammalian heart where linoleic acid (18:2) predominates

Glycolipids

• Lipid with monosaccharide(s) attached; general structures shown

  • Amphipathic but neutral or negatively-charged (if sulfate group added)

• Form glycocalyx with glycoproteins

• Two types of eukaryotic membranes:

  • Glycosphingolipids (animal cells) and glycoglycerolipids (plant cells)

Gangliosides

• Conjugated molecules comprised of glycosphingolipids and glycans

• Abundant within human brain, especially: GM1, GD1a, GD1b, and GT1b

Steroids

• Non-linear structure built on a tetracyclic platform (aka steroid nucleus)

  • Generally lack fatty acids, a departure from other membrane lipids

• Involved with cell signaling (example: hormones as primary messengers)

• Cholesterol is the most common/abundant steroid

  • Comprises 30-40% of a eukaryotic cell’s plasma membrane

  • Used to synthesize bile salts (for dietary protein and lipid digestion) and other hormones

Why are Steroids Considered Lipids?

• Similar solubility characteristics: hydrophobic and water-insoluble

• Found naturally alongside other lipids within fat

  • Lipid comes from the Greek word lipos, which means fat

• Synthesized from acetyl-CoA – same starting material used to synthesize fatty acids

membranes

Membranes and Membrane Transport

Glycerophospholipids – The Most Common Phospholipid

• A 1,2-diacylglycerol that has a phosphate group esterified at carbon atom 3 of the glycerol backbone is a glycerophospholipid, also known as a phosphoglyceride or a glycerol phosphatide

• They are essential components of cell membranes and are found in small concentrations in other parts of the cell

• All glycerophospholipids are members of the broader class of lipids known as phospholipids

• Phosphatidic acid is found in small amounts in most natural systems and is an important intermediate in the biosynthesis of the more common glycerophospholipids

Headgroups of ‘Phosphatides’

• The phosphate, together with such esterified entities, is referred to as a “head” group

• Phosphatides with choline or ethanolamine are referred to as phosphatidylcholine (aka lecithin) or phosphatidylethanolamine, respectively

• These phosphatides are two of the most common constituents of biological membranes

• Other common head groups found in phosphatides include glycerol, serine, and inositol

• Another kind of glycerol phosphatide found in many tissues is diphosphatidylglycerol (cardiolipin)

• In cardiolipin, a phosphatidylglycerol is esterified through the C-1 hydroxyl group of the glycerol moiety of the head group to the phosphoryl group of another phosphatidic acid molecule

Distribution of the Most Abundant Lipids in the Eukaryotic Cell Membranes

Membranes Are Asymmetric and Heterogeneous Structures

Several Spontaneously Formed Lipid Structures

• Micelles formed from an amphipathic lipid in water position the hydrophobic tails in the center of the lipid aggregation with the polar head groups facing outward

• Amphipathic molecules that form micelles are characterized by a unique critical micelle concentration, or CMC

• Below the CMC, individual lipid molecules predominate

• Nearly all the lipid added above the CMC, however, spontaneously forms micelles

• Micelles are the preferred form of aggregation in water for detergents and soaps

The Fluid Mosaic Model Describes Membrane Dynamics

Peripheral Membrane Proteins Associate Loosely with the Membrane

Single Transmembrane Helix Spanning Proteins

Multi-Transmembrane Proteins

• Bacteriorhodopsin is composed of seven transmembrane a-helical segments connected by short loops

• Nearly all of this protein is embedded in the membrane

• Only the short loops connecting helices are exposed to solvent

• A retinal chromophore (a light-absorbing molecule, shown in blue) lies approximately parallel to the membrane and between the helical segments

• A proline residue (red) induces a kink in one of the helical segments (green)

Membrane Protein ‘Tilt’

• Not all the embedded segments of membrane proteins are transmembrane and oriented perpendicular to the membrane pairs

• The glutamate transporter homolog has “reentrant” helices (orange) and interrupted helices (red)

• Several of the transmembrane helices deviate significantly from the perpendicular

Beta Barrel Transmembrane Proteins

Proteins Can Be Anchored to the Membrane by Covalently Coupled Lipids

• Thioester-linked fatty acyl anchors:

  • This type of fatty acyl chain linkage has a broader fatty acid specificity than N-myristoylation

  • Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the C16 and C18 chain lengths being most commonly found

• Thioester-linked prenyl anchors:

  • Polyprenyl (or simply prenyl) groups are long-chain polyisoprenoid groups derived from isoprene units

  • Prenylation of proteins destined for membrane anchoring can involve either farnesyl or geranyl-geranyl groups

Glycosyl Phosphotidylinositol (GPI) Anchors

• GPI groups modify the C-terminus of a target protein via an ethanolamine residue linked to an oligosaccharide, which is linked in turn to the inositol phosphoethanolamines, N-acetylgalactose, or mannosyl residues moiety of a phosphatidylinositol

• The oligosaccharide typically consists of a conserved tetrasaccharide core of three mannose residues and a glucosamine, which can be altered by addition of galactosyl side chains of various sizes and extra phosphoethanolamines, N-acetylgalactose, or mannosyl residues

dietary digestion

Dietary Lipids

• Found within foods that contain vegetable oils or fats (animal and plant)

  • Some spices and herbs also good dietary sources

• Inorganic food additives (like salt and sugar) lack this biomolecule

• Cooking may alter lipid characteristics but doesn’t eliminate it from the food

More on Essential Fatty Acids

• Only two for humans: alpha linolenic acid (omega-3) and linoleic acid (omega-6)

  • Precursors to local hormones and important for neural cell membranes

• These molecules are usually constituents in dietary triacylglycerols in vegetable oils, nuts, etc.

• Deficiencies are rare, though omega-6 consumption > omega-3 consumption

Omega Fatty Acids in Nuts – Walnuts

• LA (alpha-linolenic acid) is the plant-based omega-3 fatty acid

• Walnuts are the clear winner in terms of omega-3 content

• Most nuts are much higher in omega-6 than omega-3, which can be a concern if not balanced in the diet

• Ratios closer to 1:1 are considered better for reducing inflammation

Omega Fatty Acids in Fish – Mackerel

• Omega-3s in fish are primarily EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) – more potent than ALA found in plants

• Fish generally have much lower omega-6 compared to omega-3, making them anti-inflammatory and beneficial for heart and brain health

• Farmed fish tend to have higher omega-6 than wild-caught due to their grain-based diets

Digestion: Contributions from the Mouth

• Lingual lipase is secreted by von Ebner’s glands (~sublingual) of the tongue

• Facilitates the digestion of fats by breaking down triglycerides into diacylglycerols and free fatty acids

• Most activity occurs when the enzyme is transported with food to the stomach where it is more active under acidic conditions

• Key enzyme in digesting milk fats in newborns

• Unlike other mammalian lipases, is highly hydrophobic and readily enters fat globules

• Both proteases and lipases belong to the hydrolase family of enzymes

• Hydrolases: enzymes that catalyze the hydrolysis of chemical bonds using water

  • Proteases (also called peptidases or proteinases):

    • Hydrolyze peptide bonds in proteins

  • Lipases:

    • Hydrolyze ester bonds in lipids (triglycerides)

• So, while they act on different substrates (proteins vs. lipids), they’re both hydrolases because they use water to break bonds in their respective target molecules

In the Stomach

• Gastric lipases cleave triacylglycerols (TAGs) into diacylglycerols (DAGs)

  • Responsible for 10-30% of fat degradation

• Enzymatic activity and stomach contractions form a lipid emulsion

In the Small Intestine

• Non-enzymatic bile salts further emulsify fats, generating smaller droplets

  • Also destabilize bacterial membranes, killing some food pathogens

• Bile salts help with absorption of fat-soluble vitamins (A, D, E, and K)

  • Vitamins A, D, and E are NOT precursors to coenzymes

  • Vitamin K is; essential for carboxylase activity

  

Lipases and Monoacylglycerol in the Stomach

• Pancreatic lipases sequentially cleave any remaining TAGs and DAGs

  • Generate free fatty acids (FAs) and monoacylglycerol (MAG)

• Free fatty acids and MAG then moved across cell’s plasma membrane

• FABP = fatty acid binding protein (embedded transporter)

• FATP = fatty acid transport protein (cytoplasmic)

• SER = smooth endoplasmic reticulum

More on Post-Digestion

• About 95% of dietary fatty acids are absorbed by the small intestine

  • Rest thought to provide nutrition to intestinal microbiota

• Dietary fatty acids are stored (as TAGs in adipose tissue) for later use

• Metabolism will involve the B-oxidation pathway and cellular respiration

Chylomicrons in Lipid Packaging and Transport

• Chylomicrons are lipoprotein particles formed in enterocytes (intestinal cells) after triglycerides are broken down into fatty acids and monoglycerides

• These are then re-esterified and packaged with water soluble apolipoproteins into chylomicrons, which are released into the aqueous lymphatic system

• A coordinated hormonal response – especially involving Cholecystokinin (CCK), insulin, and glucagon-like peptide-1 (GLP-1) and GLP-2 – supports the digestion, absorption, and repackaging of dietary fats into chylomicrons

• These lipoprotein particles also contain fat-soluble vitamins and cholesterol and deliver dietary fat to adipose tissue (for storage) or muscles (for energy)

metabolism

Brief Review of Metabolism

• Combustion (molecules burned up via complex chemical processes) of simple molecules to generate energy; known as catabolism

• Metabolic pathways share intermediates

  • Example: acetyl CoA

• Cellular respiration is a series of metabolic pathways that convert carbon fuels into CO₂ and H₂O to generate energy (i.e., ATP)

Getting “Ready” for Metabolism

• If stored triacylglycerols supply the fatty acids, then lipolysis involved

  • Hormones epinephrine and glucagon induce lipases

  • Mobilization selective as fatty acids with shorter chains and more unsaturation used first

• Carbon fuel transported from adipose tissue by globular protein albumin

• Fatty acids use FABPs to enter muscle cells

B-Oxidation Pathway

• Occurs in cytoplasm of prokaryotes, but in mitochondria of muscle cells

  • Also observed in eukaryotic adipocytes but considered minor

• Consists of four repeating steps (each round shortens the FA’s hydrocarbon chain by 2 carbons):

  • Oxidation by FAD
    Hydration

  • Oxidation by NAD⁺

  • Thiolysis by coenzyme A

• Generates products that can then enter cellular respiration

Biochemical Activity Within the Muscle Cells

• Bringing fatty acids into mitochondria requires activation and channels

• Activation achieved by attaching fatty acid to coenzyme A (HS-CoA)

  • Catalyzed by enzyme acyl CoA synthetase

  • Reaction reversible but driven forward by ATP hydrolysis

• Acyl CoA crosses outer mitochondrial membrane (OMM) via ion channel

• Since ATP → AMP, equivalent to loss of 2 ATP

Carnitine in Acyl Transport

• 95% of carnitine is located within skeletal muscles

• Activities at this channel are the rate-limiting step (i.e., slowest part of the metabolic pathway)

B-Oxidation Pathway, Step 1: Oxidation by FAD

• First reaction is oxidation of the B-carbon by a dehydrogenase

  • Enzyme = acyl CoA dehydrogenase

  • Reaction generates trans double bond between carbon-2 and -3

  • Products: trans-delta²-enoyl CoA and FADH₂

• Acyl CoA = fatty acid (acyl group) attached to coenzyme A (CoA)

B-Oxidation Pathway, Step 2: Hydration

• Second reaction is hydration of trans-delta²-enoyl CoA by a hydratase

  • Hydration is stereospecific 

  • Enzyme = enoyl CoA hydratase

  • Reaction generates hydroxyl group; single bond between carbon-2 and -3

  • Product: L-3-hydroxyacyl CoA

B-Oxidation Pathway, Step 3: Oxidation by NAD⁺

• Enzyme = L-3-hydroxyacyl CoA dehydrogenase

• Reaction converts hydroxyl group to keto group at carbon-3

• Products: 3-ketoacyl CoA and NADH

B-Oxidation Pathway, Step 4: Thiolysis by Coenzyme A

• Fourth reaction is cleavage of 3-ketoacyl CoA by thiol group of a second coenzyme A molecule

  • Enzyme: B-ketothiolase

  • Reaction cleaves 3-ketoacyl CoA into two molecules

  • Products: acetyl CoA and a fatty acid chain two carbons shorter

• Thiolysis = chemical reaction in which a sulfhydryl (R-SH) functional group cleaves one compound into two

Side Note about Cellular Respiration

• Steps 1-3 in B-oxidation are structurally similar to reactions 6-8 in the citric acid cycle (i.e., oxidation by FAD, hydration, and oxidation by NAD⁺)

• Both pathways occur within mitochondrial matrix

  • Reduced coenzymes donate electrons into electron-transport chain

• Reactions 6-8 in citric acid cycle

What Happens to the Products?

• Acetyl CoA can enter citric acid cycle (generate ATP)

• NADH and FADH₂ can donate electrons to electron-transport chain

• Shortened FA (acyl group) continues to be metabolized via B-oxidation

• Final thiolysis products for an even chain fatty acid: two acetyl CoA

Revisiting Hexanoate (C₆H₁₂O₂)

• Combusting this saturated fatty acid generates 36 ATP

  • (3 acetyl CoA x 10 ATP)* + (2 NADH x 2.5 ATP) + (2 FADH₂ x 1.5 ATP)

  • 30 ATP + 5 ATP + 3 ATP = 38 ATP - 2 ATP (for activation) = 36 ATP

• *each acetyl CoA that enters the citric acid cycle generates 1 ATP, 3 NADH, and 1 FADH₂

What About Odd Chain Fatty Acids?

• Metabolism also occurs via muscle’s B-oxidation pathway

• Final thiolysis products: acetyl CoA and propionyl CoA (a 3-carbon molecule)

• Propionyl CoA not an intermediate for cellular respiration, but a carboxylase and a mutase convert it into succinyl CoA, which can enter citric acid cycle

But Not All Fatty Acids are That Simple to Metabolize

• Very long chain fatty acids (22 or more carbons) sent to peroxisome (organelle containing oxidative enzymes) first

  • Acyl group shortened via peroxisomal B-oxidation pathway

  • Then transported to mitochondria for standard B-oxidation pathway

• Unsaturated fatty acids require additional enzymes to shift the position and configuration of the carbon-carbon double bond(s)

  • Metabolism occurs within same location as B-oxidation pathway

Regulation of the B-Oxidation Pathway

• Steps 1-3 are each controlled via feedback inhibition

  • For example, L-3-hydroxyacyl CoA suppresses enoyl CoA hydratase

• The B-oxidation pathway also responds to:

1. NADH and acetyl CoA (both suppress activity)

2. PGC-1a (activates transcription factors, increasing gene expression)

3. Cytoplasmic malonyl-CoA (suppresses activity)

Glycerol Metabolism

• Liberated from triacylglycerols during dietary lipid digestion and lipolysis

• Sent to liver, where it is phosphorylated by glycerol kinase

• Product then oxidized and isomerized into glyceraldehyde 3-phosphate

  • Molecule directed into glycolysis (generate ATP) or gluconeogenesis (generate glucose), depending on cell’s needs

fatty acid synthesis

Fatty Acid Synthesis

• Occurs in cytoplasm of prokaryotes, as well as in cytoplasm of adipocytes and liver cells of eukaryotes

• Utilizes acetyl CoA obtained from mitochondria

• Problem: inner mitochondrial membrane = impermeable

• Solution: citrate-malate shuttle

How Many Acetyl CoA Must be Transported?

• Depends on hydrocarbon length; acetyl CoA a 2-carbon carrier

• To synthesize palmitate (16:0), would need 8 acetyl CoA

• Shortcut: (#C/2)

Biochemical Activity Within the Adipocytes

• Acetyl CoA condensed with bicarbonate, generating malonyl CoA

  • Catalyzed by enzyme acetyl CoA carboxylase I (ACC)

  • Reaction driven forward by ATP hydrolysis

• This is the committed step in fatty acid synthesis

  • Consequently, will be used to regulate overall pathway

  

Regulation of Acetyl CoA Carboxylase I (ACC)

Biochemical Activity Continued…

• Acyl group (malonate) then transferred to an acyl carrier protein (ACP)

  • ACP serves as a scaffold; intermediates attached to the sulfhydryl end

• Transfer catalyzed by enzyme malonyl-CoA-ACP transacylase (MAT)

  • Generates malonyl-ACP, upon which the FA is built

• Scaffold = temporary structure used to construct a molecule

Fatty Acid Synthesis

• Now the fatty acid will be synthesized via:

1. Condensation

2. Reduction of the carbonyl group

3. Dehydration

4. Reduction of the double bond

   1. Steps repeat until palmitate (16:0) made

• Pathway extends the hydrocarbon chain two carbons at a time

  • Generates a saturated, even chain fatty acid

Step 1: Condensation

• First reaction is condensation of malonyl ACP with acetyl ACP

  • Enzyme = B-ketoacyl synthase

  • Reaction extends acyl group by two carbons

  • Products: acetoacetyl ACP and CO₂

Step 2: Reduction of Carbonyl Group

• Second reaction is reduction of carbonyl group by a reductase

  • Enzyme = 3-ketoacyl-ACP reductase

  • NADPH is the electron donor

  • Reaction converts keto group to hydroxyl group at carbon-3

  • Product: D-3-hydroxybutyryl ACP

Step 3: Dehydration

• Third reaction is dehydration of D-3-hydroxybutyryl ACP by a dehydratase

  • Enzyme = B-hydroxyacyl ACP dehydratase

  • Reaction generates trans double bond between carbon-2 and -3

  • Product: crotonyl ACP and H₂O

Step 4: Reduction of the Double Bond

• Fourth reaction is reduction of the C=C bond by a reductase

  • Enzyme = enoyl ACP reductase

  • NADPH is the electron donor

  • Reaction generates single bond between carbon-2 and -3

  • Product: butyryl ACP

What Happens Next?

• Lengthened acyl group undergoes another round

  • Butyryl ACP condenses with a new molecule of malonyl ACP (Step 1)

  • Forms C₆-B-ketoacyl ACP; acyl group now contains 6 carbons

  • Reduction, dehydration, and reduction (Steps 2-4) then follow

• Repeats until C₁₆-acyl ACP formed

But What Happens to C₁₆-Acyl ACP?

• C₁₆-acyl ACP = substrate for enzyme palmitoyl-protein thioesterase (PPT)

• PPT cleaves thioester linkage connecting 16C acyl-CoA with ACP, freeing palmitate (16:0)

Let’s Consider Palmitate

• B-oxidation pathway:

  • Metabolizing palmitate generates:

    • 8 acetyl CoA

    • 7 NADH + 7 FADH₂ + 7H⁺

  • If those components were then funneled into cellular respiration, we’d generate:

    • [(8 acetyl CoA x 10 ATP) + (7 NADH x 2.5 ATP) + (7 FADH₂ x 1.5 ATP)] - 2 ATP (activation) = 106 ATP 

• Fatty acid synthesis:

  • Synthesizing palmitate requires:

    • 8 acetyl CoA

    • 14 NADPH + 13H⁺

    • 7 ATP

What About Synthesizing Odd Chain Saturated FAs?

• Synthesis occurs in cytoplasm via same anabolic pathway

• Propionate (contains 3 carbons) transferred to an ACP (not shown below)

  • Condensed with malonyl-ACP, generating 3-oxovaleryl-ACP (has 5 carbons)

• Each subsequent round will add 2 carbons to acyl group (i.e. 7 → 9 → 11)

Where Does Propionyl-CoA Come From?

• B-oxidation of odd-chain fatty acids

• Oxidation of cholesterol

• Catabolism of specific amino acids:

  • Valine, isoleucine, methionine, threonine

But Not All Fatty Acids Are That Simple to Synthesize

• Generating a product with more than 16 carbons involves endoplasmic reticulum:

  • Uses anabolic enzymes called elongases attached to organelle’s membrane

• Generating an unsaturated fatty acid also involves that organelle

  • Desaturase introduces a cis double bond at a particular location

• Humans have front-end desaturases (delta4-6 and 9) but not methyl-end desaturases (like w³ and w⁶)

Revisiting Cis-Polyunsaturated Fatty Acids (PUFAs)

• Recall both linolenic acid (w³) and linoleic acid (w⁶) are essential fatty acids for humans

  • Must come from diet, as cannot introduce double bonds beyond carbon-9

• Humans have enzymes to convert PUFAs within a family (from a medium chain omega-3 to a long (or very long) chain omega-3, for example) but rather inefficient

  • Process involves acyl chain extension and front-end desaturases

Comparison of B-Oxidation and Fatty Acid Synthesis

cholesterol and steroids

Quick Review

Trans and Saturated Fats in Health

• Why are trans fats worse for you than saturated fats?

  • “Trans fats raise (bad) LDL cholesterol levels slightly less than saturated fats do,” says Lichtenstein. “But saturated fats also raise levels of high density lipoprotein (HDL) or “good” cholesterol, and trans fatty acids don’t.” Trans fats may actually lower HDL. Thus, some researchers say trans fats are worse

    • Alice H. Lichtenstein, Dsc, professor of nutrition at Tufts University in Boston

• Atherosclerosis – AKA; hardening of the arteries

  • Caused by build-up of fats, cholesterol, and other substances in and on the artery walls

Polar Bears, Seals, and Triacylglycerols

• Triacylglycerols in animals are found primarily in the adipose tissue (body fat), where it serves as a depot or reservoir of stored energy

• Monoacylglycerols and diacylglycerols also exist, but they are far less common than the triacylglycerols

• Most natural plant and animal fat is composed of mixtures of simple and mixed triacylglycerols

• The adult polar bear feeds almost exclusively on seal blubber (largely composed of triacylglycerols), thus building up its own triacylglycerol reserves

• Through the Arctic summer, the polar bear maintains normal physical activity, roaming over long distances, relying almost entirely on its body fat for sustenance, burning as much as 1 to 1.5 kg of fat per day

• It neither urinates nor defecates for extended periods; all the water needed to sustain life is provided from the metabolism of triacylglycerols because oxidation of fatty acids yields carbon dioxide and water

One Palmitoyl-CoA – 106 ATP and 123 Water Molecules

Triacylglycerols as Fly “Antifreeze”

• Acetylated triacylglycerols (triglycerides in which one of the acyl groups is an acetyl) occur only rarely in animals

• However, goldenrod gall flies remain viable during freezing winter weather (typically as cold as -10^oC) in Ontario, Canada, thanks to accumulations of acetyl triacylglycerols (acTAGs) – as much as 46% of their total triglycerides

• These triglycerides remain in a liquid state in the harsh Canadian winters, providing freeze tolerance to the flies

Cholesterol

Isoprenes Make Up Terpenes

• Terpenes are a class of lipids formed from combinations of two or more molecules of 2-methyl-1,3-butadiene, better known as isoprene (a five-carbon unit that is abbreviated C5)

• A monoterpene (C10) consists of two isoprene units, a sesquiterpene (C15) consists of three isoprene units, a diterpene (C20) has four isoprene units

• Isoprene units can be linked in terpenes to form straight-chain or cyclic molecules, and the usual method of linking isoprene units is head to tail (Figure 8.12)

• Monoterpenes occur in all higher plants, whereas sesquiterpenes and diterpenes are less widely known

• The triterpenes are C30 terpenes and include squalene and lanosterol, two of the precursors of cholesterol and other steroids

• Monoterpenes occur in all higher plants, whereas sesquiterpenes and diterpenes are less widely known

• The triterpenes are C30 terpenes and include squalene and lanosterol, two of the precursors of cholesterol and other steroids

Lingo of Isoprenes

• An isoprenoid contains oxygen, while an isoprene is a hydrocarbon

• Same concept: a terpenoid contains oxygen, while a terpene is a hydrocarbon

• The terpenoids (aka isoprenoids) are estimated to make up 60% of known natural products

• Looks like a lipid because of glycerol, but instead of an ester there’s an ether, and instead of an acyl chain, looks like an isoprene chain

Polyprenols

• Long-chain polyisoprenoid molecules with a terminal alcohol moiety are called polyprenols

• The dolichols, one class of polyprenols consist of 16 to 22 isoprene units and, in the form of dolichyl phosphates

• They function to carry carbohydrate units in the biosynthesis of glycoproteins in animals

• Polyprenyl groups serve to anchor certain proteins to biological membranes

Steroids – Synthesized From Isoprenes, Terpenes, or Both?

• Steroids: terpene-based lipids

• Based on a common structural motif of three 6-membered rings and one 5-membered ring all fused together

• This molecular family affects an amazing array of cellular functions

A Diverse Group of Steroids

Steroid Hormones Derived from Cholesterol

Biosynthetic Pathway of Testosterone in the Human Body

ketone bodies

The Major Organ Systems Have Specialized Metabolic Roles

• Essentially all cells in animals have the set of enzymes common to the central pathways of intermediary metabolism, especially the enzymes involved in the formation of ATP and the synthesis of glycogen and lipid reserves

• Nevertheless, organs differ in the metabolic fuels they prefer as substrates for energy production

• Important differences also occur in the ways ATP is used to fulfill the organs’ specialized metabolic functions

What Are Ketone Bodies, and What Role Do They Play in Metabolism?

• Acetone, acetoacetate, and b-hydroxybutyrate are known as ketone bodies

• These three metabolites are synthesized primarily in the liver but are important sources of fuel and energy for many tissues, including brain, heart, and skeletal muscle

• During periods of starvation, ketone bodies may be the major energy source for the brain

• Acetoacetate and B-hydroxybutyrate are normal substrates for kidney cortex and for heart muscle

Ketone Body Synthesis in the Liver Mitochondria

• The first reaction – the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA – is catalyzed by thiolase

• This is the same enzyme that carries out the thiolase reaction in B-oxidation, but here it runs in reverse

• The second reaction adds another molecule of acetyl-CoA to give 3-hydroxy-3-methylglutaryl-CoA, commonly abbreviated HMG-CoA

• HMG-CoA is converted to acetoacetate and acetyl-CoA by the action of HMG-CoA lyase in a mixed aldol-Claisen ester cleavage reaction

• A membrane-bound enzyme, B-hydroxybutyrate dehydrogenase, then can reduce acetoacetate to B-hydroxybutyrate

• Acetoacetate and B-hydroxybutyrate are transported through the blood from liver to target organs and tissues, where they are converted to acetyl-CoA