lec 2 (mcbride) - lipids, carbs, part 1: basic structures

monosarccharides

• simplest carbohydrates

  • carbohydrates = carbon-based molecules high in OH groups

    • empirical formula = (CH₂O)_n

    • can have additional groups or modifications

    • better described as polyhydroxy aldehydes and ketones (and their derivatives)

• monosaccharides are aldehydes or ketones that contain 2 or more OH groups

• smallest monosaccharides composed of 3 carbons

• monosaccharides exist in many isomeric forms

• also known as “simple sugars”

• monosaccharides = carbohydrates that are 3-7 carbons in length

monosaccharide nomenclature

• nomenclature based on carbon-chain length

  • 3 Cs = trioses

  • 4 Cs = tetroses

  • 5 Cs = pentoses

  • 6 Cs = hexoses

  • 7 C = heptoses

• nomenclature also based on the identity of the most oxidized group

  • keto group = ketose

  • aldehyde group = aldose

sugars commonly found in cells

• glyceraldehyde

• ribose

• glucose

• dihydroxyacetone

• ribulose

• fructose

monosaccharides exist in a variety of isomeric forms

constitutional isomers

• molecules with identical molecular formulas that differ in how the atoms are ordered

stereoisomers

• molecules that differ in spatial arrangement but NOT bonding order

• have either D or L configuration (most monosaccharides from vertebrates have D config)

• can be enantiomers (mirror images of each other) or diastereoisomers (NOT mirror images of each other)

  • enantiomers → all Cs have altered chirality

  • diastereoisomers → if only some Cs have altered chirality

• # possible = 2ⁿ where n = # of asymmetric C atoms

common monosaccharides

have multiple asymmetric carbon atoms

epimers

they are diastereoisomers differing in configuration only at a single asymmetric center

• glucose + mannose = epimers; C2 has altered chirality

• glucose + galactose = epimers; C4 altered

• mannose + galactose = diastereoisomers b/c altered chirality at 2 AND 4

overview of isomeric forms of monosaccharides

glucose and fructose are what type of isomers

constitutional

same molecular formula but DIFFERENT connectivity

monosaccharides and rxns

each end of a monosaccharide can react together

• aldehyde can react with alcohol to form hemiacetal

• ketone can react with alcohol to form hemiketal

monosaccharides are predominately in…

ring formation inside cells (in solution)

• in aqueous soln, aldehyde or ketone group of a sugar molecule tend to react with OH of the same molecule → closing molecule into ring

glucose forms a __ ring

pyranose

• called pyranose b/c of similarity to pyran

• anomers = isomers that differ at a new assymmetric carbon formed on ring closure (alpha & beta)

fructose forms a __ ring

furanose

• called furanose b/c of similarity to furan

most common monosaccharides exist primarily…

in their ring forms

how many asymmetric carbons?

open chain = 4 (everything but end Cs)

ring = 5

polysaccharides or complex carbohydrates are ___

multiple monosaccharides

• oligosaccharides = sugars that contain 2 or more monosaccharides linked by O-glycosidic bonds

• disaccharides (such as sucrose) consist of 2 sugars

identity of glycosidic bond is determined by…

carbons linking the monosaccharides

• “reducing sugars” have anomeric forms due to possessing a reducing end

  • reducing end = has a free anomeric C that can form the open chain form

  • nonreducing end = hsa an anomeric C in a glycosidic linkage that CANNOT convert to open chain form

sucrose

formed from glucose and fructose

• sucrose = disaccharide of sugar cane or sugar beets that consists of glucose linked to fructose

  • the anomeric C of glucose is linked to the anomeric C of fructose

  • configuration is α for glucose and β for fructose

  • not a reducing sugar

  • can be cleaved by sucrase (invertase)

maltose

disaccharide of 2 glucose molecules

• α-1,4-glycosidic linkage = glycosidic linkage between the α-anomeric form of C-1 on one sugar and the OH oxygen atom on C-4 of the adjacent sugar

• maltose = disaccharide resulting from the hydrolysis of large oligosaccharides that consist of 2 linked glucose molecules

  • joined by α-1,4-glycosidic linkage

  • can be hydrolyzed to glucose by maltase (α-glucosidase)

lactose

formed from galactose and glucose

• lactose = disaccharide of milk that consists of a galactose linked to glucose

• can by hydrolyzed by lactase in humans beings and β-galactosidase in bacteria

what is the glycosidic linkage

α,1,1-glycosidic bond (the C that is connected to OH and NOT methyl)

what is used to assemble larger macromolecules

monomeric building blocks or subunits

• sugars → polysaccharides, glycogen, and starch (in plants)

• fatty acids → fats and membrane lipids

• amino acids → proteins

• nucleotides → nucleic acids

each polymer is formed from small molecules (called monomers) linked together by covalent bonds

glucose is stored as…

macromolecule glycogen to provide energy in times of need

• free glucose CANNOT be stored b/c high concentrations will disturb the cell’s osmotic balance

• polysaccharides (glycans) = large polymeric oligosaccharides formed by the linkage of multiple monosaccharides

  • plays role in energy storage and structural integrity

• homopolymer = polymer in which all the monosaccharide units are the same

glycogen

is a large, branched polymer of glucose residues

• most common homopolymer in animal cells

• storage form of glucose

• most glucose units are linked by α-1,4-glycosidic linkages

• hydrolyzed by α-amylase

• branching increases the surface area to allow better access for enzymes to rapidly breakdown glycogen

glycogen is stored in the…

liver

glycogen granules in the cytoplasm of liver cell

glycosidic linkages in mammals

determine polysaccharide structure: glucose storage in mammals

• α-1,4 linkages favor bent, helical structures → more suitable for storage

glycosidic linkages in plants

β-1,4 linkage favor straight chains → optimal for structural purposes

glycogen and energy production

glycogen provides glucose for energy production

• when cells need more ATP than they can generate from food molecules taken in from the bloodstream → they break down glycogen

• glycogen = shorter-term storage of energy

• glycogen has the largest stores in liver and muscle

• during fasting, liver cells release glucose derived from breakdown of their glycogen stores → bloodstream for use by other tissues while muscle cells hoard their supplies for their own use

• an avg adult humans stores enough glycogen for only about a day of normal activities (energy demands) but enough fat to last for nearly a month

glycogen phosphorylase

is an enzyme which breaks down glycogen when cells need more glucose

fatty acids

• have 4 major physiological roles

  • fatty acids are fuel molecules

  • fatty acids are building blocks of phospholipids and glycolipids

  • many proteins are modified by the covalent attachment of fatty acids which functions to target proteins to membrane locations

  • fatty acids derivatives serve as hormones and intracellular messengers

fatty acid structure

determined by double bonds in hydrocarbon tail

• hundreds of different kinds of fatty acids exist

• some have one or more double bonds in their hydrocarbon tail = unsaturated

  • double bond = rigid and creates a kink in the chain; rest of the chain is free to rotate around the other C-C bonds

• NO double bonds = saturated

• all fatty acids have a carboxyl group (COOH) at one end and a large hydrocarbon tail at the other

fatty acids are the building blocks for…

lipids

triacylglycerols (TAGs)

• triacylglycerols (TAGs) are the storage form of fatty acids as uncharged esters with glycerol

• fatty acids are stored in cells as an energy reserve (fats and oils) through an ester linkage to glycerol to form triaglycerols also known as triglycerides

how to identify the chemical composition of the fatty acids within the lipid molecule

first # = # of Cs

second # = # of double bond

triglyceride structure

determined by fatty acid composition

• 3 fatty acid chains are linked to this glycerol thru ester bonds

• simple triglyceride = when the 3 fatty acid tails are identical

• mixed triglyceride = when the fatty acid tails are different

lipids

lipids with saturated fatty acids have higher energy density than unsaturated fatty acids

• straight chains can be packed together very tightly → allowing them to store energy in a compact form

• lipids with saturated fatty acids = solid at room temp (fats)

• lipids with unsaturated fatty acids = liquid at room temp (oils)

TAGs and energy stores

TAGs are highly concentrated energy stores

• triacylglycerols (neutral fats, triglycerides) = uncharged esters of fatty acids with glycerol

  • stored mainly in adipose tissue

  • stored also by muscle for energy needs

what are the identities of the fatty acids in this lipid?

TG(16:0,18:1,18:3)

TAGs are physically stored in…

adipose tissue

• adipose tissue = fuel-rich, white tissue that is located throughout the body, notably under the skin (subcutaneous fat) and surrounding internal organs (visceral fat)

• adipocytes = fat cells that make up adipose tissue

  • major site of triacylglycerol accumulation

  • specialized for triacylglycerol synthesis, storage and mobilization into fuel

TAGs form…

lipid droplets

• lipid droplets = large globules formed by the coalescence of triacylglycerols

  • may occupy most of the adipocyte volume

  • surrounded by a phospholipid monolayer and proteins required for lipid metabolism

TAG degradation…

produces free fatty acids

• lipases = intestinal enzymes that degrade triacylglyceroles to FFAs and monoacylglycerol

  • secreted by pancreas

FFAs used as…

fuel by many tissues

glycerol is converted to…

glycolytic intermediate in the liver

• glycerol is absorbed by the liver → phosphorylated → oxidized to dihydroxyacetone phosphate and isomerized to glyceraldehyde 3-phosphate

fatty acids are transported…

via bloodstream for energy (ATP) in tissues

• low glucose levels in the blood trigger the hydrolysis of the triacylglycerol molecules in fat droplets to free fatty acids and glycerol

• these fatty acids enter the blood stream → bind to abundant blood protein serum albumin

• special fatty acid transporters in the plasma membrane of cells oxidize fatty acids, such as muscle cells → pass fatty acids into cytosol → goes into mitochondria for energy production

fat as an energy source

fat is the most efficient energy source

• oxidation of a gram of fat releases twice as much energy as oxidation of gram of glycogen

• fatty acids provide energy to all tissues in the body, except the brain

• brain must rely on circulating glucose or ketone bodies when available b/c fatty acids are poorly utilized by the brain

phospholipids are a…

major class of membrane lipids

• phospholipids = major constituents of cell membranes

• hydrophilic head and hydrophobic fatty acid tails

• 2 of the -OH groups in glycerol are linked to fatty acids while the 3rd -OH group is linked to the phosphoric acid

• phosphate carries a negative charge → further linked to one of a variety of small polar groups such as choline

polar groups found in phospholipids

• serine

• ethanolamine

• choline

• glycerol

• inositol

common phospholipids found in cell membranes

• phosphatidylserine

• phosphatidylcholine

• phosphatidylethanolamine

• phosphatidylinositol

• diphosphatidylglycerol

what type of lipid is the following molecule

PC

lipid aggregation

based on chemical properties of fatty acids are critical in biology

• in water fatty acids can form either a surface film or small, spherical micelles → their derivatives can form larger aggregates held together by hydrophobic forces

• triacylglycerols form large spherical fat droplets in the cell cytoplasm

• phospholipids and glycolipids form self-sealing lipid bilayers → basis for all cell membranes

common class of lipids

steroids

• common multiple-ring structure

• cholesterol → found in many cell membranes

• testosterone → male sex hormone

OH group of cholesterol interacts with…

with phospholipids within cell membranes

• cholesterol = steroid built from 4 linked hydrocarbon rings

  • contains a linked hydrocarbon tail at one end and -OH group at the other end

  • oriented parallel to fatty acid chains of phospholipids in membranes

  • -OH group interacts with phospholipid head groups