Carbohydrates

Exam 3

Introduction

• Carbohydrates are the most abundant biological molecules

• Saccharides (Greek “sugar)

1. Monosaccharides- the basic carbohydrate unit, “the simple sugars”

2. Polysaccharides- multiple monosaccharides linked together 

• Roles of carbohydrates:

1. Energy Sources 

2. Structural materials 

3. Facilitate protein interaction 

Classification of Monosaccharides- The Simple Sugars

• Monosaccharides are classified according to their carbonyl group and the number of carbon atoms

• Carbonyl group

1. If the carbonyl group is an aldehyde then the monosaccharide is an aldose

2. If the carbonyl group is a ketone, then the monosaccharide is a ketose

• Number of Carbons

- 3 Carbons- Triose

- 4 Carbons- Tetrose

- 5 Carbons- Pentose 

- 6 Carbons- Hexose 

- 7 Carbons- Heptose 

- 8 Carbons- Octose 

Saccharides

• They are composed of C, O, H according to the formula (C*H2O)n where   n >- 3

• Monosaccharides are classified by their number of carbon atoms 

• Basic carbohydrate units are monosaccharides 

  • Polymers of monosaccharides units are polysaccharides 

• Triose: C3H6O3

• Tetrose: C4H8O4

• Pentose: C5H10O5

• Hexose: C6H12O6

• Heptose: C7H14O7

• Octose: C8H16O8

Monosaccharides 

Two Families: 

• Aldose: contains an aldehyde group 

• Ketose: Contains a ketone group 

  • aldose and ketose are to be isomers of each other, they have the same chemical formula but different structures… they tend to have diff. properties and reactivities 

Fischer Projection

• Fischer projection: a two dimensional representation for showing the configuration of tetrahedral stereocenters 

D & L 

• According to the conventions proposed by Fischer (Bottom -OH is…)

  • D-monosaccharide: a monosaccharide that, when written as a Fischer projection, has the -OH the right of the chiral carbon 

  • L-monosaccharide: a monosaccharide that, when written as a Fischer projection, has the -OH on the left of the chiral carbon 

Monosaccharides 2

• Contain one or more chiral carbons

  • Active isometric forms (meaning they are isomers)

• Simple aldose: glyceraldehyde

  • 1 chiral carbon

  • 2 isometric forms

• A molecule with n chiral centers can have 2^n stereoisomers

Enantiomers

Stereoisomers that are mirror images

Epimers

• Monosaccharides that differ by the stereochemistry about one carbon atom are called epimers 

  • diff. (H and (-OH) localizations/arrangements 

• Why are Galactose and Mannose not epimers? b/c there’s more than one rearrangement 

Important Aldoses 

Important Ketoses

Aldose/Ketone Interconvesion

• Aldose/Ketose Interconvesion is possible through the catalytic conversion of triose phosphate isomerase 

• Triose Phosphate Isomerase- catalyzes isomerization reaction of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate

  • basically rearranges stuff 

Aldose/Ketone Interconvesion Example

Glycolysis

Mechanism for Triose Phosphate Isomerase

• TRI is an example of a catalytically perfect enzyme 

  • The rate of the bimolecular reaction between enzyme and substrate is diffusion controlled such that formation of product occurs as quickly as substrate and enzyme collide 

Cyclization of Aldoses and Ketoses

• Aldoses/Ketoses can form cyclic structures 

• 2 important function groups play an important role in this process:

1. Carbonyl (aldehyde/ketone)

2. Alcohol (-OH) group 

How does this happen mechanistically? 

Cyclization of Aldoses and Ketoses 2

Reaction of an alcohol with:

(a) An aldehyde to form a hemiacetal 

(b) A ketone to form a hemiketal 

Cyclization of D-Glucose to form glycopyranose

• Example: Aldose (aldehyde functional group and alcohol functional group)

• Chemistry: C1 - aldehyde, C5 - alcohol - Form a 6 membered ring structure “pyranose” 

Cyclization of D-fructose to form fructofuranose

• Example: Ketose (ketone functional group and alcohol functional group) 

• Chemistry: C2 - ketone, C5 - alcohol - Form a 5 membered ring structure “furanose” 

Basic Ring Structures

(a) Pryan and (b) furan ring systems

• (a) Six-membered sugar ring is a “pyranose”

• (b) Five-membered sugar ring is a “furanose” 

Possibility of Multiple Cylizations

Cyclizations are not exclusive for specific forms 

• In many monosaccharides, there are two or more reactive hydroxyl groups that can serve to attack an aldehyde or ketone 

• The nature of the substituents on the carbonyl and hydroxyl groups and nature of asymmetric carbon determine pyranose vs furanose form 

  • Aldehexose sugars prefer the pyranose structure 

  • Ketohexose sugars prefer the furanose structure 

Conformations 

The two chair conformations of B-D-glucopyranose

Furanose and pyranose rings are NOT planar

Monosaccharides can be converted to several derivative forms

Sugars are VERY reactive

• A variety of chemical and enzymatic reactions produce derivatives of the simple sugars 

• Some of the most common are: 

- Sugar acids 

- Sugar alcohols 

- Deoxy sugars 

- Sugar esters 

- Amino sugars 

- Acetals, ketals, and glycosides 

Monosaccharides can be converted to several derivative forms 2

Figure 7.9 Oxidation of D-glucose to sugar acids

Sugar Derivatives

• Sugars undergo reactions typical of aldehydes and ketones 

  • These reactions have important physiological consequences 

1. Oxidation of aldehydes produces carboxylic acids 

2. Oxidation of primary alcohols yield uronic acids 

3. Reduction 

• Aldoses and ketoses produce ribitols 

• Hydroxyl groups replaced by hydrogens 

4. Amination- replacing of -OH groups with -NH2

Sugar Derivatives- Oxidation

Oxidation

• Reducing Sugars- sugars containing a free aldehyde 

• Oxidation of 

  • the aldehyde group 

  • aldonic acid (“onic acid”)

• Oxidation of 

  • primary alcohol group 

  • uronic acid (“uronic acid”)

Sugar Derivatives- Reduction (SLIDE 28)

• Reduction (gain electrons)

• Aldehydes are reduced to form alcohols 

Sugar Alcohols:

Sugar Alcohols: Xylitol

Sweeter in sugarless gum and candies

Sugar Alcohols: Glycerol

Important components in lipids

Sugar Alcohols: myo-Inositol

Important components in lipids

Amination

• Important constituent of glycoproteins and glycolipids 

  • Proteins and lipids with covalently attached carbohydrates 

Many possible functions: 

1. Enzymes 

2. Transport proteins 

3. Receptors 

4. Hormones 

5. Structural proteins 

Cyclic Carbohydrates

• A hydroxyl end can react with the carbonyl of the aldehyde or ketone within a monosaccharide to form cyclic compounds 

• All monosaccharides with five or more carbon atoms in the backbone occur predominantly in the cyclic structure 

• a: C1-OH down, B: C1-OH up 

Anomeric Carbon

• Monosaccharides exist almost entirely as five- and six-membered rings 

  • anomeric carbon: the carbonyl carbon used for cyclic formation 

  • anomers: carbohydrates that differ in configuration only at their anomeric carbons 

• a: C1-OH down, B: C1-OH u[

• Important nature of anomeric carbon as it relates to glycosidic bond formation joining two monosaccharides forming disaccharides and polysaccharides

Glycosidic Bond

• Glycoside: a carbohydrate in which the -OH of the anomeric carbon is replaced by -OR

  • those derived from furanoses are furanosides; those derived from pyranoses are pyranosides

  • glycosidic bond: the bond from the anomeric carbon to the -OR group, can be a or B-glycosidic bonds

Glycosidic Bond 2

Glycosidic Bonds

Important bond formation in linking monosaccharides to form polysaccharides 

• Have properties of hydroxyls (OHs/alcohols)

• If there’s a free anomeric carbo, then it’s capable of reducing reactions 

Polysaccharides

• Also called glycans 

• Consist of monosaccharides linked together by glycosidic bonds 

  • formation of glycosides: The anomeric carbon of a sugar combines (condenses) with an alcohol 

    • a or B-glycosides 

Reducing Ends

• Monosaccharides have reducing ends 

• Upon formation of a glycosidic bond, the anomeric carbon becomes non-reducing 

• A reducing end can still participate in ring opening, yielding a free carbonyl 

Important Di- & Polysaccharides

Disaccharides 

1. Lactose 

2. Sucrose 

Polysaccharides 

3. Cellulose 

4. Chitin 

5. a-amylose 

Lactose

• Disaccharide

• Occurs in milk

• Composed of galactose and glucose

• Both galactose and glucose exist as a B-anomer

• Linkage is B (1 → 4)

• Glucose molecule contains a reducing end, therefore lactose is a reducing sugar

  • Quick energy source and can break/release two sugars

Lactose 2

• Lactose intolerance?

  • Symptoms: gas, belly pain, bloating 

• What causes it?

  • Deficiency in enzyme lactase, not enough is produced in the small intestines to aid in the breakdown of glucose 

  • Not a food allergy 

• What is lactose? 

  • Glycoside hydrolase that is involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers 

• Asian lineages that don’t produce or drink milk tend to lack lactose, making them lactose-intolerant 

• Another example with Russians for ethanol and not being able to stomach alcohol 

Sucrose

• Disaccharide 

• Most abundant disaccharide 

• Table sugar 

• Composed of glucose and fructose 

• Glucose is in the a-anomeric form and fructose is in the B-anomeric form 

• Linkage is a (1 → 2) 

• Fructose has a non-reducing end, therefore sucrose is a non-reducing sugar '

  • Sugar canes are an example… highly prevalent in Florida

7.4 What is the structure and Chemistry of Polysaccharides

Functions: storage, structure, recognition

• Nomenclature for polysaccharides is based on their composition and structure 

• Homopolysaccharide- a polysaccharide that contains only one kind of monosaccharide 

  • same units of monomeric sugar copied # number of times in a polymer 

• Heteropolysaccharide- a polysaccharide made of several monosaccharides 

  • diff. sugars coexisting in a polysaccharide 

• Starch and glycogen are storage molecules 

• Chitin and cellulose are stuctural molecules 

• Cell surface polysaccharides are recognition molecules 

Cellulose (know structure)

• Polysaccharide- homopolysaccharide

• Primary structural component in plants 

• Accounts for half the carbon in the biosphere 

• Linear molecule of up to 15,000 D-glucose residues 

• Glucose molecules are in the B-anomeric form 

• Linkage is B (1 → 4)

  • Building block of plant cell walls

  • Most commonly observed and most widely distributed in nature 

  • Polymer of glucose

  • Extremely steep polymer, it is building into self-assembling fibers…  fibers is what provides stability to plants & allows them to grow, withstand harsh environmental conditions and high temp. 

Cellulose 2

• Parallel cellulose chains form sheets with interchain H-bonds 

• Stacks of the fibers occur having exceptional strength and are water insoluble 

• Cellulases are enzymes within symbiotic microorganisms found in herbivores that hydrolyze the B (1 → 4) linkages of cellulose

  • Humans can not digest cellulose, fiber 

  • Animals that consume plants have cellulases, enzymes in gums that can break down cellulose. We don’t have these enzymes 

  • Cellulose is still a very important component of our diet. Helps us have proper digestive processes in our stomach. Important to consume green food… if you don’t have access/don’t have enough, there are fiber supplements

Fibers

• Classification of dietary fibers: 

  • Based on their ability to dissolve in water 

1. Soluble 

2. Insoluble 

• Act by changing the nature of the contents of the GI tract and by changing how other nutrients and chemicals are absorbed 

• Uses for fiber:

  • nutritional purposes

  • treatment of various gastrointestinal disorders

  • health benefits as lowering cholesterol levels, reducing risk of colon cancer, and losing weight 

• Fiber supplements 

  • Benefiber

  • Metamucil

Chitin (know structure)

• Polysaccharide- Homopolysaccharide 

• Principal structural component of the exoskeletons of insects, crustaceans, & spiders, & in the cell walls of most fungi and algae

• Homopolymer of N-acetylglucosamine 

• N-acetylglucosamine molecules are in the B-anomeric form 

• Linkage B (1 → 4)

  • very interesting monomeric structure b/c in its monomer sugar residues you have amide

  • if cellulose is transparent, chitin will have dark appearance 

Starch (know structure)

• Starch- storage polysaccharide in plants with mixture of a-amylose and amylopectin 

  • starch is a combination of these 2 polymers

  • in both cases, we have glucose linked with a a-1,4 glycosidic bonds 

• a-amylose is a linear polymer of a (1 → 4) linkages 

  • Isomer of cellulose

•  Amylopectin can contain 10^6 glucose molecules

  • Consists mainly of a (1 → 4) linkages, but can form a branched molecule with a (1 → 6) linkages

  • people that work on starch prefer to grow potatoes (main source of starch) with very small amounts of amylopectin b/c it’s harder for our body to digest

Glycogen

• Storage polysaccharide of animals 

• Present in all cells 

  • Mainly skeletal muscle and the liver 

  • liver breaks down glycogen and produces monomeric sugars when we need energy 

• More highly branched than amylopectin 

  • important for high stability of glycogen in liver 

  • needs higher energy to digest polymer and produce monomeric sugars 

Amylopectin & Glycogen 

• a (1 → 6) branch points 

  • amylopectin: every 24 to 30 glucose residues

  • glycogen: every 8-12 glucose residues

Starch

• Starch is processed to produce many of the sugars in processed foods

• Glycogen and amylopectin have the same structure, but the former has about one branch point per ten 1,4-alpha bonds, compared to about one branch point per thirty 1,4-alpha bonds in amylopectin

• Amylopectin is synthesized from ADP-glucose while mammals and fungi synthesize glycogen from UDP-glucose

• Starch is the most common carbohydrate in the human diet

• Starch is a great form of energy, but when eaten in too high of quantities, results in weight gain

• Some starch turns to sugar very quickly raising blood glucose faster than table sugar

Breakdown of Starch

taste sweet? monomeric sugars are hydrolyzed 

1. Amylase (starch hydrolyzed by this enzyme that is present in saliva)

• Enzyme is saliva that hydrolyzes the a (1 → 4) glycosidic bonds of starch 

2. a-glucosidase 

• Hydrolyzes one glucose residue at a time 

3. Debranching enzyme 

• Hydrolyzes a (1 → 4) and a (1 → 6) glycosidic bonds 

Glycogen Breakdown 

1. Glycogen phosphorylase- cleaves glycogen’s a (1 →4_ bonds sequentially inward from non-reducing ends 

2. Glycogen debranching enzyme- cleaves a (1 → 6) bonds

Why carb-free diets can be dangerous:

• Brain functions on glucose! Need certain levels of glucose to maintain healthy brain function 

• Other issues results from low carbs potentially: 

  • Kidney stones- produce more uric acid creating solubility issues with urine expulsion 

  • Gout- high levels of uric acid are also associated with crystallization and association with joins, causing painful inflammation 

• So the dietary answer: 

  • For the general population, a balanced diet with appropriate exercise is the best approach at getting healthy 

  • Carbohydrate calories should be 20% of total energy consumption 

Keto diet (unsat. fats… no sugar, more fats (butter))

• largely excludes carbs

• dangerous diet b/c body will entirely change metabolism… sugar is important

• Kurouski lab: mice on vegan diet, keto diet, American diet

• Interested in relationship b/w neurodegeneration and diet, not stress

• inject 6-hydrozopamine in stratum and make them rotate… number of rotations will indicate degree of degeneration of neurons because the more neurons that are degenerated in one area, the greater the mice will rotate

• mice that were on keto diet developed Parkinson’s much faster

• saturated fats, not cholesterol (trigger neurodegeneration)

• activated MI is what kills cells in the brain 

• mice on keto diet have extremely large liver because it needs enzymes to metabolize high amounts of fats consumed… food looks like toothpaste 

Glycosaminoglycans

• Important glycosaminoglycan components of connective tissue and synovial fluid 

• Component of cell surface and extracellular substance in blood vessel walls and brain: Important in would healing, critical role in development 

  • heterosugars have more complex structures

  • sulfanated glycosaminoglycans are very important… present in seaweed and their consumption can be useful to treat lots of diseases related to retina 

Glycoproteins

Glycosylated proteins provide exclusive properties to proteins, primarily immunoproception 

• Glycoproteins- proteins with carbohydrate contents 

1. Proteoglycans 

• Composed of proteins and glycosaminoglycans 

• Membrane- associated and secreted proteins of eukaryotic cells are almost always glycosolated

  • perform very important signal transduction 

• The oligosaccharides are covalently attached to the proteins by either O-glycosidic or N-glycosidic bonds

Glycoproteins 2

2. Peptidoglycan and bacterial cells walls

• major building blocks of bacterial cell walls… self-assemble forming tough, rigid membrane structure around bacterial cell walls → allow bacteria to withstand harsh environmental conditions 

• very elastic, can be broken down by bacterial enzymes, which allow bacteria to proliferate 

• sugar capsule: additional layer of protection (luckily, not all bacteria have)

• acetalbactrobalminae (one of most dangerous classes) has sugar capsule 

• Professor caught this in Egypt… he was immunocompromised 

• had it in his bloodstream, not a single antibiotic could help because sugar capsule prevents access to bacteria 

• Ray Young used bacteriophages to treat him

• bacteria cells very quickly mutate and change their sugar capsule to withstand bacteriophage attack… changed daily

• antibiotics is class of biological molecules that can be incorporated in cell walls and prevent proliferation of bacteria… discovered from petri dish

• penicillin discovered in ‘30s, used in WW2… more killed by wounds instead of bullets 

• put gunpowder in wounds… only way to disinfect

• sepsis is when bacteria gets in bloodstream, rate or survival dec. 

Sugars in Immune Response

• Carbohydrates can be directly recognized by T cells or participate in T-cell stimulation as components of T-cell epitopes 

  • carbs are key players in immune system 

• T-cell recognition of carbohydrate antigens takes place via their presentation by major histocompatibility complex pathways on antigen-presenting cells 

Blood and Carbohydrates ABO

• Blood transfusion:

  • presence of antibodies and antigens (have to care about, will kill each others RBCs

  • only blood group fully identical to individual will be transfused 

Transfusion Relationships among ABO blood types

Cell-cell interaction

Selectin: transmembrane glycoproteins that mediate the attachment between leukocytes and epithelial cells. Recognize and bind specific oligosaccharides on cell-surface glycoproteins. Responsible for “capture of circulating leukocytes in blood.

• lectins interact with sugars present in diff. cells 

• building blocks: allow cells in our bodies to stay integrated and form tissues 

Virus-cell interactions 

Sugars play important roles in recognition of viruses

• Influenza virus binds to sialic acid residues (Neu5Ac) that are present on cell surface glycoprotein

  • internalized by cells through endocytosis 

  • cut off bond, proliferate towards nucleus where they inject their 

• After the virus penetrates the cell membrane, another viral protein, neuraminidase (sialidase), cleaves the glycosidic bonds to the sialic acid residues, freeing the virus to infect the cell. Inhibitors of this enzyme such as Tamiflu and Relenza are important anti-influenza agents

Glucose Regulation

• High level of glucose in blood is dangerous. It is lowered through secretion of insulin by B cells of pancreas

• Insulin promotes uptake of glucose by cells lowering its level in blood

• Low levels of glucose are also dangerous, especially for neurons 

• Upon low glucose level in blood, glucagon is released which promotes hydrolysis of glycogen in liver 

Helpful Study Hints

Look for commonalities in structures:

1. know glucose and galactose (linear to cyclic forms); recognize that lactose is a disaccharide composed of glucose and galactose have B (1 → 4) linkage 

2. Chitin is aminated glucose polymers with B (1 → 4) linkage 

3. a-amylose and cellulose are isomers 

• a-amylose has a (1 → 4) linkages 

• cellulose has B (1 → 4) linkage 

Bioremediation

• Jeff Fonda? uses soldier pliers (pliers that can consume a ton of biological material in a very short time frame) b/c they grow very quickly so people think that soldier pliers can be used to bioremediate dangerous wastes that are produced by humans

• Trying to see if soldier pliers can be used to bioremediate prions

  • prion proteins will change structure of proteins… can self-assemble (very toxic) & cause many diseases in humans as well as in animals, including chronic waste disease 

  • If you hunt, do not eat the brain or lymph nodes of animals 

  • if blood of deer that has prions drops on a plant, plant will possess prions and if next year we consume plant, we will be impacted by prions 

  • prions can stay on plants for years, they are very stable structures 

• One of many problems we try to address in the state of Texas is screwworm fly

  • was in Texas in 70s and 80s, can lay 200-300 eggs on fresh wounds (infestations) 

  • larvae that hatch from these eggs will burrow inside tissue and will develop in animals 

  • at late stages, become big (3-4x bigger than grain of rice)

  • causes cow death in 5-7 days 

  • nuclear rxn… fly can go around 12 miles, how it spreads 

  • Aggie professor proposed to grow and cultivate flied and x-ray larvaes. Flies that hatch from this larvae will be sterile… will mate with wild flies, but produce no fertile eggs. Approach worked and problem was pushed away from Texas. U.S. had partnership with Panama and with war in South Panama… all flied got pushed there. What took 18 years to do was back in 2 days because of COVID. Fly back in TX, people are losing cattle 

  • monitor cattle and diff. size larvae