Chapter 7: Carbohydrates & Glycobiology

A five-membered sugar ring is called what?

a furanose - come from pentoses like fructose

Heparin vs heparan sulfate

- Heparin is a linear polymer, 3-40 kDa - heparan sulfate (HS) is a heparin-like polysaccharide, but attached to proteins - these biomolecules have very high neg charge density (bc of sulfates) - prevent blood clotting by activating protease inhibitor antithrombin > binding to various cells regulates development, formation of blood vessels > can also bind to viruses and bacteria and decrease their virulence

Are low-carb diets safe?

- NO - no organism or culture has evolved eating high protein, low carb diets - weight loss over long term is equivalent to that seen in a mixed diet > no advantage - may have short-term benefit for diabetics

When drawing the Fischer projections of trioses, what is important?

- OH location

Dihydroxyacetone

a ketotriose

A six-membered sugar ring is called what?

a pyranose - come from aldohexoses (six-carbon with an aldehyde group)

Formations of Hemiacetals and Hemiketals is the basis of what?

cyclization of sugars

Since they do not dissolve, what do glycogen and starch do in cells?

- form granules

General functions of carbohydrates

1. energy source and storage 2. structural component of cell walls and exoskeletons 3. informational molecules in cell-cell signaling

List the steps of carbohydrate absorption

1. monosaccharides are absorbed into the intestinal epithelium 2. they cross the cell 3. enter the capillaries into the blood 4. they make their way into the portal vein which takes sugar to the liver 5. from the liver, the blood enters the hepatic vein, and eventually makes its way into the heart

Hyaluronic acid (hyaluronan)

- composed of GlcUA (glucuronate) and GlcNAc (N-acetylglucosamine - GlcUA-(β 1-->3)-GlcNAc-(β 1-->4)- ^ this means that the GlcUA binds to position 3 on GLcNAc, which binds to position 4 on the next GlcUA - 250-25,000 residues

#7: Helps to manage diabetes

- glycemic effect > some fibers slow food movement from stomach to small intestine > causes slower increase in blood sugar > produces a more moderate insulin response > much healthier than a quick spike in blood sugar - can make a person less susceptible to type 2 diabetes

Enantiomers

-stereoisomers that are mirror images

Ribofuranose conformations

1) C2-endo envelope conformation 2) C3-endo envelope conformation 3) twist conformation

What are the 5 main health effects of sugar? (Most of the diseases that sugar is associated with have not been validated conclusively)

1) Obesity 2) Diabetes 3) Hypertension 4) Behavior 5) Dental caries

Give the six mutations that can occur if one of the six steps in GAG synthesis is messed up.

1) Progeroid-type Ehlers-Danlos Syndrome (hyperextensible joints, fragile skin, premature aging) 2) short stature or frequent joint dislocations 3) Neuropathy (nerve damage) 4) Skeletal defects 5) Bipolar disorder or diaphragmatic hernia 6) Bone deformations as large bone spurs

Structural homoglycans

1) cellulose 2) chitin

What are the 2 drugs used to treat type 2 diabetes? What do they do?

1. Acarbose (Precose) 2. Miglitol (Glyset) - prevent glucose from being generated from starch breakdown - prevent rise is blood sugar after meal (diabetics want to avoid a rise in blood sugar)

While cellulose is the most abundant type of fiber, what are the other 3 types?

1. Hemicellulose - cereal fibers - insoluble 2. Pectins - fruits & veggies, esp apples and pears - also used as a thickener (jelly) - soluble 3. Gums & mucillage - food additive - stabilizer - soluble

What are the 5 important disaccharides to know?

1. Maltose Glucose-(α 1-->4)-glucose 2. Lactose Galactose-(β 1-->4)-glucose 3. Sucrose Glucose-(α 1-->2)-β-fructose 4. Cellobiose β-Glucose-(β 1-->4)-glucose 5. Trehalose Glucose-(α 1-->1)-α-glucose

What are the two types of oligosaccharide linkages?

1. O-linked - attached to hydroxyl of Ser or Thr 2. N-linked - attached to amide nitrogen of Asn

What are the 5 "common" carbohydrates in biochemistry?

1. Ribose (standard 5-C sugar) 2. Glucose (standard 6-C sugar) 3. Galactose (epimer of glucose) 4. Mannose (epimer of glucose) 5. Fructose (ketose form of glucose)

#3: Sucrose

Glucose-(α 1-->2)-β-fructose - table sugar - nonreducing sugar (no free anomeric carbon) - refined form sugarcane -naturally present in fruits and veggies - broken down in intestine (ultimately body gets glucose + fructose) - honey has same nutritional value as sucrose (both are made of glucose & fructose), except in honey, some are linked, while some are free glucose and fructose

#1: Maltose

Glucose-(α 1-->4)-glucose - product of starch hydrolysis

SKIP GLYCOMICS!!!!!!!!!!

HELL YEAH!!!! only go through slide 231

What noncovalent force helps to hold cellulose together?

Hydrogen bonding in cellulose

Honey

Bee's Processing: 1) water content reduced 30-60% to 15-19% (hypertonic - no bacteria or spores can grow in it, so it won't spoil) 2) invertase enzyme hydrolyzes most of the sucrose into glucose and fructose 3) glucose oxidase produces small amounts of gluconic acid Content: - honey is supersaturated with sucrose (1% by weight), fructose (38%), and glucose (31%) - 13C NMR reveals mixture of α and β forms of glucopyranose and fructofuranose - however, most fructose (67%) is fructopyranose (rare)

Carbohydrates are produced from ____ and ____ via photosynthesis in plants

CO2 and H2O

General formula for carbohydrates

Cn(H2O)n

Which of the stereoisomers is biologically important?

D-form

#2: Lactose

Galactose-(β 1-->4)-glucose - milk (dairy) sugar - after infancy, some lose ability to digest (lactose intolerance)

Addition of N-acetyl-glucosamine is reversible; it is removed by what?

GlcNAc-ase

Sugar acids from glucose - Aldonic acid Ex) D-Gluconate

Gluconate is the carboxylic acid form of D-glucono-𝛿-lactone, which is the "reducing sugar" form of glucose - to get gluconate, oxidize C1

#5: Trehalose

Glucose-(α 1-->1)-α-glucose - nonreducing sugar - widely found in nature (bacteria, fungi, insects, plants, invertebrates) - mushrooms: 10-15% dry weight - insect hemolymph (insect blood sugar) - protects organisms against dryness, freezing, and osmopressure (stabilizing proteins and unsaturated fatty acids) - naturally found in several foods like honey, mushrooms, lobster, shrimp, bread, and beer (also added as sweetener, stabilizer, and thickener) - could be future treatment for Huntington's Disease

Addition of N-acetyl-glucosamine (GlcNAc) is carried out by what?

O-GlcNAc Transferase, which is a highly conserved enzyme

What is the size range for carbohydrates?

Small as glyceraldehyde (90 g/mol) to as large as amylopectin (200 million g/mol)

Cats have a deletion of what gene?

TAS1R2 - so they may not be able to taste sweetness at all

What genes encode for sweetness receptors?

Tas1R2 and Tas1R3 - expressed on gustatory cells in taste buds - generates a signal that results in an electrical signal sent to the brain which is sensed as "sweet"

Nutritive sweeteners

a) sugars b) sugar alcohols c) truvia (from leaves of stevia plants) - contains natural sweetener Rebiana - 250-450x sweeter than sucrose - no calories

Glyceraldehyde

an aldotriose

After cyclization, the former carbonyl carbon becomes a new chiral center, called the _____ carbon

anomeric - the anomeric carbon is usually drawn on the right side - when the former carbonyl oxygen becomes a hydroxyl group, the position of this group determines if the anomer is alpha (α) or beta (β)

Aldehyde and ketone carbons are _____

electrophilic

The alcohol oxygen atom is ______

nucleophilic

The concentration of GlcNAc reflects what?

nutrient abundance

What compound gives tomatoes their firmness?

pectin

What enzyme destroys pectin?

polygalacturonase

What are the two families of membrane proteoglycans (Heparan Sulfate ProteoGlycans, HSPG)?

syndecans and glypicans

#4: Cellobiose

β-Glucose-(β 1-->4)-glucose - component disaccharide of cellulose

What is the other name for cellulase?

β-glucosidase

Drawing monosaccharides

- chiral compounds are usually represented by Fischer projections - horizontal (left to right) bonds are pointing toward you; vertical (up to down) bonds are projecting away from you

At what residues do oligosaccharides typically attach to on proteins (in glycoproteins)?

- common connections occur at Ser, Thr, and Asn

In what foods are amylopectin and amylose most abundant?

(*having more branch points makes you easier to digest*) - amylopectin is rich in sticky rice, corn and potatoes - easily digested in small intestine due to number of branches - amylose is found in beans, legumes, and whole grains - amylose has a greater surface area than amylopectin and is more resistant to digestion > so it proceed to the colon, where it is broken down by amylose-fermenting bacteria such as Prevotella and Lachinospira -> this produces short chain fatty acids (SCFA) such as butyrate

Fructose in diet

- "fruit sugar" - sweetest of all sugars - made by plants - naturally found in fruits, sap, honey - isolated in large quantities from corn syrup - body feeds fructose into glycolysis through 3 extra reactions

Heparin

- (GlcUA-2-sulfate)-(α 1-->4)-N-sulfo-glucosamine-6-sulfate-(α 1-->4) - not a constituent of connective tissues - exclusively located in intracellular granules of mast cells in arterial walls - natural anticoagulant > released during injury > binds to antithrombin III, which is involved in terminating the clotting process, inhibiting coagulation > prevents excessive clotting - used to inhibit clot formation in post-surgical patients

Each core protein in the aggrecan complex has what attached to it?

- 30 keratan sulfates (GlcNAc-6-sulfate)-(β 1-->3)-Gal-(β 1-->4)- - 100 chondroitin 6-sulfates (GalNAc-6-sulfate)-(β 1-->4)-GlcUA-(β 1-->3)-

Recommended amounts of sugar

- 5-10% of total calories should come from sugars (mono + disaccharides) - more sugar may displace protein, fat, vitamins, and minerals

High protein, Low carb diets

- Atkins diet from 1960s: based on diets developed in 1940s for diabetics, before availability of insulin - people on low-carb diets intake 1500-1700 cal/day; lose a lot of weight - low intake because 1) high protein intake suppresses appetite 2) resulting ketosis further suppresses appetite

#1: Obesity

- BMI = or > 30 - obesity risk increases as sugar intake increases - not only factor (sometimes thin people actually consume more sugar)

Storage homoglycans (AKA homopolysaccharides that are used to store sugar)

- D-glucose is stored intracellularly in polymeric forms: 1) plants and fungi store starch (amylose + amylopectin) 2) animals store glycogen

What defects can occur if there are mutations in the degrative enzymes in the GAG synthesis pathway?

- The degradative enzymes are defective, so incompletely degraded glycosaminoglycans accumulate 1) Scheie syndrome - joint stiffening, normal intelligence and lifespan 2) Hurler syndrome - enlarged internal organs, heart disease, dwarfism, mental retardation, early death)

What are glucosinolates?

- a class of glycosides that protect against herbivory ex) mustard, relish, kale, broccoli

What is the connection between artificial sweeteners and obesity?

- a daily consumption of diet soda is associated with a 67% greater risk of developing type 2 diabetes - consuming artificial sweeteners such as saccharin may alter gut microbes - this can lead to metabolic disturbances, glucose intolerance, and obesity

Adult lactose metabolism - gene

- a gene for lactose absorbance (LA) is an autosomal dominant gene - originally all humans were lactose intolerant in adulthood - the cultural practice of keeping dairy herds was a selective factor, provided advantage for the LA genotype - appeared in Europe ~4,000 years ago - selective pressure: people with mutation would product 20% more fertile offspring than those without

What is erythropoietin (EPO)?

- a glycoprotein hormone released by the kidneys - stimulate the production of erythrocytes (RBCs) - 165 AA with 3 N-linked and one O-linked (Ser) oligosaccharides > it's 40% carbohydrate by weight > the oligosaccharides enhance the stability of the hormone in blood - can be produced recombinantly to treat anemia, especially following cancer chemotherapy - has been abused by endurance athletes to increase RBCs and oxygen-carrying ability of blood - labs can detect natural vs recombinant EPO in drug tests, by the glycosylation patterns

What is chitin?

- a linear structural homoglycan polysaccharide of N-acetylglucosamine - [GlcNAc-(β 1-->4)-GlcNAc]n - linear unbranched chains held together by extensive interchain H-bonding - every other sugar is inverted upside down

What are the risks of a low-carb diet?

- a low-carb diet will make the body enter ketosis > very dangerous > only seen during starvation, in chronic alcoholics, and in untreated diabetics > involves severe metabolic derangements > increases rate of dehydration, constipation, kidney stones, hyperlipidemia, optic neuropathy, osteoporosis > impairs higher order mental processes - high protein diets lead to an increase in calcium excretion, leading to decreased bone mass and osteoporosis

What is raffinose?

- a trisaccharide of galactose-(α 1-->6)-glucose-(α 1-->5)-fructose - beans, cabbage, brussels sprouts, asparagus, broccoli, whole grains - digested by α-galactosidase (α-GAL), not found in human digestive tract - fermented into CO2, methane, and H2 by bacteria - digestive aid Beano contains α-GAL

Glycoproteins constitute about what fraction of all mammalian proteins?

- about 1/2

Carb content: - grains

- abundant in starch - 1-2 g fiber/serving - more in whole grains

What is the role of hyaluronic acid (hyaluronan)?

- acts as shock absorber (vitreous humor of eye) and lubricant (synovial fluid)

Common functional groups on carbohydrates

- aldehydes = aldose (has aldehyde functionality) - ketones = ketose (has ketone functionality)

Recommended Carbohydrate Intake

- all except fiber have 4 cal/g - 20-35 g/day recommended (AI = 14 g/1000 cal/day) - 45-65% of total calories daily should come from carbs > RDA 130 g/day, based on avg minimum amount of glucose needed by the brain - <10% of total daily cals from sugars (most cals from carbs should be from starch)

Lactose intolerance =/= milk allergy. Milk allergy is what?

- allergic reaction to the protein casein

Carb content: - meats

- almost no carbs

What is cellulose?

- an extracellular, fibrous structural polysaccharide > rigid, strong, insoluble in water > held together by extensive interchain H-bonding > cotton, wood - present in plant cell walls - makes up 50% of all organic material on earth

Where is chitin found?

- arthropod exoskeletons - fungal cell walls - often associated with inorganic materials or proteins

Stereoisomers

- atoms connected in the same order, but differ in spatial arrangement - two types: enantiomers + diastereomers

Structure of peptidoglycan

- attached to each NAM are four linked amino acids (a peptide) > of those, D-glutamic acid, D-alanine, and diaminopimelic acid are never found in proteins; they are found only in peptidoglycan (D forms???? woah!!!) - the peptides are covalently attached to one another to hold sugar chains together

What are the treatments for lactose intolerance?

- avoid dairy - enzyme supplements (Lactaid)

Why are glycogen and starch insoluble?

- because of their high molecule weight

Describe the digestion of carbohydrates

- begins in mouth - salivary amylase released; breaks starch down into maltoses - ceases in stomach - minor hydrolysis of starch by HCl - resumes in small intestine (maltase, sucrase, and lactase are made by the small intestine) > Pancreatic amylase breaks down starch into maltoses > Maltase breaks down maltose into 2 glucoses > Lactase breaks lactose down into galactose + glucose > Sucrase breaks down sucrose into glucose + fructose - then, monosaccharides are absorbed by the intestine

Do low-carb diets "work" ?

- body is designed to use carbs as primary fuel - if carbs are not available, then it uses fat (both ingested and stored) - body acts as if it is in "starvation" mode > burns fat for energy > burns glycogen stores first (to use the sugar), then converts muscle protein to glucose

How are disaccharides often named?

- by the organization and linkage, or by a common name Ex) the disaccharide formed upon condensation of two glucose molecules via (1 --> 4) bond is α-D-glucopyranosyl-(1-->4)-D-glucopyranose also known as maltose

Monosaccharides in diet

- called "simple sugars" since they are the simplest carbs - building blocks for more complex carbs 1) Glucose 2) Fructose 3) Galactose

Reducing sugars

- can act as a reducing agent - have a free anomeric carbon ex 1) aldehyde can reduce Cu2+ to Cu+ (Fehling's test) ex 2) aldehyde can reduce Ag+ to Ag0 (Tollens' test) - these tests allow for the detection of reducing sugars such as glucose

How are oligosaccharides antigenic determinants?

- carbohydrates on cell surfaces are well known immunochemical markers ex) ABO blood groups on glycoproteins and glycolipids ex) lipopolysaccharides in gram-negative bacteria

Monosaccharide derivative 3: Sugar acids

- carboxylic acids - produced from aldoses by: 1) oxidation of C-1 to yield an aldonic acid 2) oxidation of the highest-numbered carbon to yield an alduronic acid

What is agar?

- cell wall component of red algae - contains both agarose and agarpectin

How can carbohydrates serve as informational molecules?

- cells use specific oligonucleotides to encode intracellular targeting of proteins, cell-cell interactions, cell differentiation & tissue development, and extracellular signals - there can be a variety of different sugars included, with different carbon linkages, alpha/beta linkages, and branches - with 20 different monosaccharide subunits available, there are billions of different hexameric arrangements possible

Dietary fiber (roughage) is composed majorly of what?

- cellulose

High fructose corn syrup

- cheaper + sweeter than sugar - much more quickly absorbed by the body - fructose = primarily metabolized by the liver - can be converted to fat and raise cholesterol and triglyceride levels - eating too much high fructose corn syrup can lead to insulin resistance, obesity, type 2 diabetes, and high BP

Human Milk Composition

- composition varies among women - lactose = common disaccharide in milk - 150+ different oligosaccharides (3rd most abundant component, after lactose and neutral fatty acids) - oligosaccharides not digested by infant --> play significant role in protecting against bacterial infection - prevent growth of Streptococci from vagina that could cause pneumonia, septicemia, and meningitis - may prevent attachment of microbial pathogens to the intestinal wall of newborn - may also serve as fuel for beneficial bacteria (prebiotic) - oligosaccharides NOT found in infant formula :(

#2: Diabetes

- conflicting info - appears that as sugar intake increases, so does type II diabetes - not all populations have same result - diabetes is more correlated to obesity than to sugar directly - indirect association

How do artificial sweeteners alter the gut microbiome?

- consumption of saccharin or aspartame may lead to a decrease in Lactobacillus bacteria, which are associated with decreased blood sugar - this is associated with an abundance of short-chain fatty acids (SCFAs), such as propionate, which are implicated in lipid biosynthesis - this leads to glucose intolerance, type 2 diabetes, and obesity

Carb content: - dairy

- decent amount of carbs (lactose) - milk has 12 g/cup, cheese has <6 g/serving - NO fiber!

Monosaccharide derivative 2: Deoxy & Amino Sugars

- deoxy = H replaces OH ex) β-2-deoxy-D-ribose - amino - NH2 replaces OH - the amine nitrogen is sometimes acetylated - often in glycoconjugates ex) GlcN and GalNAc

What is ketosis?

- develops when there are a lot of ketones in the blood as a byproduct of fat breakdown - acidifies blood - very dangerous

Constitutional isomer

- differ in the order of attachment of atoms

Soluble fibers

- dissolve in water - found inside and around plant cells - pectins, gums, mucilages, and some hemicellulose -oat bran, fruits, legumes, and psyllium - can bind to fat in our intestines and lower cholesterol levels (Ex: Cheerios/oatmeal)

Why are low-carb diets associated with a lowered BP?

- diuresis (water loss) 1) burning glycogen stores results in water loss 2) ketones from burning fat increase urine output

#4: Prevents diverticulosis

- diverticulosis = outpocketing of the intestines - strengthens muscles of intestines - prevents muscles of intestine from weakening and bulging out

Polysaccharides - Flux

- don't have defined molecular weight - no template is used to make polysaccharides - monomer units are added and removed as needed by the organism

Colorimetric Glucose Analysis

- enzymatic methods are used to quantify reducing sugars such as glucose - the enzyme glucose oxidase catalyzes the conversion of glucose to 𝛿-gluconolactone and hydrogen peroxide - hydrogen peroxide oxidizes organic molecules (reduced dyes) into highly colored compounds (oxidized dyes), via a peroxidase enzyme - concentrations of such compounds is measured colorimetrically - enzymes are located in a test strip to which a drop of blood is added

What is cellulase?

- enzyme that breaks down cellulose - secreted by fungi, bacteria, and protozoa - allows them to use wood as a source of glucose

#6: Prevents heart disease

- esp cereal fibers, oatmeal, legumes (beta-glucans) - foods high in fiber reduce the risk of heart disease - specifically, soluble fibers bind to cholesterol in intestines, prevents absorption, lowering serum cholesterol - high fiber foods also are normally low in fat and cholesterol

Effects of excess fiber

- excess fiber is okay - just have to maintain adequate water and mineral intake - water and minerals tend to bind to fiber, exit in feces - could potentially lead to deficiencies and dehydration - excess fiber might be fermented by intestinal bacteria, leading to flatulence

Strands of chitin are held together by what?

- extensive interchain H-bonding - this causes the formation of extended fibers similar to those of cellulose - the fibers are hard, insoluble, and cannot be digested by vertebrates - tough but flexile

What are bacterial biofilms?

- extracellular material secreted by bacteria - this material happens to be polysaccharides - allow several species of bacteria to adhere to a surface and each other - creates a barrier to antimicrobial agents

Give an example of an extracellular protein that helps to mediate the association of cells to proteoglycans

- fibronectin - associates with binding sites of both the integrin (which connects the ECM to the cytoskeleton) and the proteoglycan

What are teichoic acids?

- found in gram-positive cell walls - polymers of glycerol or ribitols joined by phosphodiester bridges - hydroxyls joined to D-Ala or saccharides such as glucose or GlcNAc - they give the cell wall its negative charge

Both agarose and agaropectin form what? What are its properties?

- gels, that are about 99.5% of water - melt at 100C, solidify below 50C - agar used to solidify media in micro labs - agarose used to form gels for molecular biology experiments

Hemoglobin A1C

- glucose meters only give current blood sugar readings - the *average* glucose level can be assessed by looking at its effect on hemoglobin - glucose transporters in RBC membranes keep intracellular and extracellular glucose levels equivalent - a non-enzymatic reaction happens between glucose and either the N-terminal Valine or side chain amino groups of Lysine resides on hemoglobin --> this is called hemoglobin glycation (NOT glycosylation, since that implies an enzyme's involvement) - the rate of this rxn is proportional to the concentration of glucose over a 3 month period (about 120 days - the lifetime of an erythrocyte)

How do glucosinolates work?

- glucosinolates are stored separately from the activating enzyme myrosinase - upon tissue damage, such as chewing, the enzyme hydrolyzes the glucosinolate, releasing isothiocyanate - isothiocyanate has a sharp taste that discourages further eating

Storage homoglycan #2: Glycogen

- glycogen is a branched homopolysaccharide of glucose - glucose monomers form (α 1-->4) linked chains - there are branch points with (α 1-->6) linkers, every 8-12 residues - more branched than amylopectin; this allows for faster metabolism - MW - several million (~ 50k Glc) (much larger than starch) - main storage polysaccharide in animals - stored in liver (10% total mass) & skeletal muscle (2%) - muscle = readily available glucose source (for exercise - since most of the sugar used during exercise is stored in the muscle, blood sugar does not usually drop due to exercise) - liver = used to regulate blood glucose level - glycogen is not component of diet

What are mucins?

- glycoproteins made by our cells - they're secreted or membrane-bound glycoproteins with a large number of O-linked oligosaccharide chains - the N- and C-terminal regions are very lightly glycosylated, but rich in cysteines, which participate in disulfide linkages within and among mucin monomers - mucins have a large central region formed of multiple tandem repeats of 10-80 residue sequences in which up to half of the amino acids are Ser or Thr - this are becomes saturated with hundreds of O-linked oligosaccharides - mucins are a key component in most gel-like secretions, serving functions from lubrication to cell signaling, to forming chemical barriers - mucins give mucus its characteristic slipperiness - at least 20 human mucin genes have been distinguished by cDNA cloning - overexpression of the mucin proteins, especially Muc1, is associated with many types of adenocarcinoma cancers, including cancers of the pancreas, lung, breast, ovary, colon, and other tissues - mucins are also overexpressed in lung diseases such as asthma, bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis

Reducing disaccharides

- glycosidic bond is formed between an anomeric carbon and a hydroxyl carbon (AKA between a hemiacetal and an alcohol) - result is an acetal and a reducing hemiacetal

"Good," "Bad," and "Net" carbs

- good: foods containing fiber > flowing broken down into sugar, leading to slower increase in blood sugar > whole grain breads, beans, fruits, and veggies - bad: foods with mostly starch and sugars > broken down more quickly, leading to a quick rise in blood sugar and insulin levels > white rice, potatoes, most breads, crackers, chips, soda, candy, cookies - net: good - bad (NOT the same as fewer carbs)

Bacterial cell walls: + or -

- gram-positive: > single thick layer of peptidoglycan (20-80 nm) > also contains teichoic acid molecules - gram-negative: > thin layer of peptidoglycan (2 nm) right outside the cell membrane > a second lipid bilayer right outside the peptidoglycan > contains lipoproteins, porin proteins, and lipopolysaccharides (LPS)

Carb content: - veggies

- has lots of starch - potato, 1/2 cup corn, peas, or beans have up to 15 g of carbs - most contain 2-3 g fiber/serving

#1: Weight Control

- has no calories - absorbs water, making you feel full (satiety) - foods high in fiber tend to be low in fat and cholesterol - eating more fiber is linked to less obesity - eating high fiber diet will help weight loss if it takes the place of fats and sweets

Explain the role of oligosaccharides and the influenza virus.

- hemagglutinin binds to sialic acid (N-acetyl-neuraminic acid, Neu5Ac) residues which are linked to galactose residues on the surface of glycoproteins (allows virus to bind to the cell it's targeting) - after penetration through the cell membrane, neuraminidase cleaves the glycosidic bond sialic acid residue > releases the virion into the cytoplasm to facilitate replication - antiviral transition state analogs Tamiflu and Relenza inhibit neurminidase

Syndecans

- heparan sulfate (HS) proteoglycan (HSPG) - syndecans are integral membrane proteins that are proteoglycans - protein has a single transmembrane domain

Glycoconjugate #2: Peptidoglycans

- heteroglycan chains linked to peptides - major component of bacterial cell walls - the heteroglycan portion is composed of alternating GlcNAc (NAG) and N-acetylmuramic acid (MurNAc / NAM) > MurNAc = lactyl group added to carbon 3 of GlcNAc (NAG) (β 1-->4) linkages connecting the units of the heteroglycan portion (every other one is flipped upside down)

Agarose

- heteropolysaccharide - repeating disaccharide of D-galactose-(Beta 1-->4)-3,6-anhydro-L-galactose - forms double helix structure - central cavity can accommodate water molecules

Heteroglycans

- heteropolysaccharides containing residues of more than one type of monosaccharide

#5: Prevents colon cancer

- high fiber diets decrease the risk of colon cancer by 40% - fiber neutralizes secondary bile acids made by bacteria, which can promote cancer development - also can bind to and trap carcinogens

What are the two main classes of polysaccharides?

- homoglycans and heteroglycans

Homoglycans

- homopolysaccharides containing only one type of monosaccharide

Blood glucose levels

- hormonal mechanisms are in place to ensure glucose remains high enough (~5 mM) to satisfy the brain's needs, but not too high as to cause damage to the body

What are proteoglycan aggregates?

- hyaluronic acid and aggrecan form huge noncovalent - they hold a lot of water (1000x the weight of the aggregate) and provide lubrication - very low frictional material - covers joint surfaces (Articular cartilage) > reduces friction > helps with load balancing

α-D-glucopyranose vs β-D-glucopyranose

- if the hydroxyl group is on the opposite side (trans) of the ring as the CH2OH moiety, the configuration is alpha --> alpha hydroxyl is down - if the hydroxyl group is on the same side (cis) of the ring as the CH2OH moiety, the configuration is beta --> beta hydroxyl is up

Monosaccharide derivative 1: Sugar phosphates

- important metabolic intermediates - name: sugar C#-phosphate (C# --> the number of the carbon to which the phosphate is attached) ex) D-glyceraldehyde-3-phosphate

Glycoconjugate #1: Proteoglycans

- root word is glycan, which means a proteoglycan is mostly made of carbohydrate chains - core proteins with glycosaminoglycans (carbohydrate chains) attached > found in the extracellular matrix (ECM) of tissues in animals > bind to cell surface proteins > may also modulate cell growth processes

What are lipopolysaccharides?

- in gram-negative bacteria, lipopolysaccharides cover the outer membrane of the cell wall - consist of 3 parts: 1) lipid A - 2 linked phosphorylated glucosamines (GlcN) - each GlcN has fatty acids attached (6 total) - lipid A portion functions as an endotoxin upon cell lysis (causes fever and potentially shock) 2) core polysaccharide - standard group of ~10 unusual sugars 3) O-side chain (O antigen) - short polysaccharide chain - varies in different bacterial strains - the O side chain is antigenic (elicits immune response) - the interaction of an antibody with the O-antigen may prevent direct attack on cell wall

D vs L carbohydrate enantiomers

- in sugars with many chiral centers, only the one that is most distant from the carbonyl carbon is designated as D (right) or L (left)

What do treatments for type 2 diabetes do?

- inhibit the enzyme maltase (α-glucosidase)

O-GlcNAc transferase dysregulation is linked to what?

- insulin resistance, diabetes, cancer, X-linked intellectual disabilities, spastic diplegia (muscle hypertonia and spasticity), and pyramidal syndrome (disruption of the pyramidal tracts that control voluntary movement)

Integrins

- integral membrane proteins - receptors for extracellular proteoglycans (mediate the association between a cell and a proteoglycan) - they link and transmit signals between the ECM and cytoskeleton > regulate cell growth, cell mobility, apoptosis, and wound healing

Why are viral protein heavily glycosylated?

- it helps them evade the immune system

What is the role of the liver in digestion?

- it is a major metabolic organ > site of carbohydrate metabolism > glycogen storage and glucose release

What happens to excess sugar (sugar that is not used for energy right away)?

- it is stored as glycogen or converted to fat

Why is cellulose difficult to digest?

- its fibrous structure and water insolubility - most animals lack the enzyme to hydrolyze (β 1-->4) linkages (cellulase)

#3: Prevents appendicitis

- keeps contents of intestinal tract flowing - prevents compaction

What enzyme do people with lactose intolerance lack?

- lactase, which digests lactose into glucose and galactose in the small intestine - unbroken lactose is not absorbed - it is fermented by intestinal bacteria - the bacteria produce acids and gas - can cause cramps, distension, bloating, flatulence, and diarrhea

What are nodulation factors?

- legumes (alfalfa, peas, soybeans) develop nodules in their roots where certain soil bacteria (rhizobia) infect - rhizobia convert ammonia in the soil to nitrate, which the plant needs to grow - rhizobia produce extracellular signal molecules call nodulation factors - very low concentrations of nodulation factors induce the host plant to develop the nodules that the rhizobia can infect - plants have nodulation-factor receptors that recognize the nodulation factor, allowing the bacteria to enter the root hair and travel to where the nodule will form - symbiotic relationship; help the plant to grow better!

Galactose in diet

- less common by itself in foods - part of lactose - not made by plants - body feeds galactose into glycolysis through 2 extra reactions

What are glycosaminoglycans?

- linear heteroglycans (polymers of repeating disaccharide units) - the glycosaminoglycans attach to the Ser of the core proteins - they make the complex elastic and resistant to compression - one of the two monomers is either: 1) N-acetyl-glucosamine 2) N-acetyl-galactosamine - they're negatively charged > uronic acids (C6 oxidation) > sulfate esters - extended hydrated molecules > minimizes charge repulsion

Amylopectin

- linear portions have (α 1-->4) bonds - branch points have (α 1-->6) bonds, which occur every 25 residues - the branches are usually 15-25 glucose residues in length - molecular weight is up to 200 million

What is the structure of cellulose?

- linear unbranched chain - [glucose-(β 1-->4)-glucose]n - every other glucose is flipped upside down - has 300-15,000 glucose residues

Linear vs. Branched Polysaccharides

- linear: straight, unbranched; one type of glycosidic bond - branched: multiple types of glycosidic bonds

Glycoconjugate #4: Glycolipids

- lipids with covalently bound oligosaccharides - they are parts of plant and animal cell membranes

Glucose in diet

- made by plants in photosynthesis - used by most body cells as chief nutrient (blood sugar in mammals is glucose) - insulin helps muscle and fat cells to absorb sugars (this lowers blood sugars) - glucagon causes an increase in blood sugar

Food sources of starch

- made in plants and fungi for glucose storage 1. grains are major source (rice, wheat, corn, etc) 2. next important are legumes (beans, peas, etc) 3. root vegetables - potatoes and yams

Pectins

- major components of plant cell walls - may function as shock absorbers - heteroglycans - core is made of (β 1-->4) linked galacturonate (GalUA) with interspersed rhamnose sugars > some GalUA may be methylated, acetylated, or have sugars such as arabinose or xylose attached - have tendency to form hydrated gels (jellies and jams!)

Monosaccharide derivatives

- many sugar derivatives are found in biological systems - some are part of oligosaccharides or polysaccharides - these include sugar phosphates, deoxy and amino sugars, sugar acids, and sugar alcohols

Extracellular matrix (ECM)

- material outside the cell - strength, elasticity, and physical barrier in tissues - main components: > proteoglycan aggregates > collagen fibers > elastin (a fibrous protein) - the ECM is a barrier for tumor cells seeking to invade new tissues > some tumor cells secrete heparinase, which degrades the ECM

What test can be done to test for lactose intolerance?

- measuring hydrogen in the breath

What are selectins (C-type lectins)?

- mediate cell-cell interactions - found in the plasma membrane of certain cells, such as in cells of the capillary endothelium - the ones on capillary endothelium allow leukocytes to bind to them via carbohydrates on the surface of the leukocyte during inflammation (this is called margination) - selectins are also expressed by embryos when they are ready to attach to the mother endometrium

Storage homoglycan #1: Starch

- mixture of two homopolysaccharides of glucose (amylose + amylopectin) - starch is the main storage polysaccharide in plants

Polysaccharides vs mono- and di-saccharides

- mono- and di- are "sugars" - polysaccharides are considered complex carbohydrates

What is the composition of bacteria biofilm?

- mostly hydrated polysaccharides such as poly-D-glucuronate, poly-N-acetylglucosamine, cellulose-like molecules, and acetylated glycans

Glycosaminoglycan (GAG) defects

- mutations in any of the enzymes needed to synthesize GAGs in humans can lead to structural defects in GAGs or proteoglycans - resulting defects can affect cell signaling, cell proliferation, tissue morphogenesis, or interactions with growth factors

What is the activating enzyme of glucosinolates?

- myrosinase

Nodulation factor structure

- nodulation factors are glycolipids - linear chain of GlcNAc-(β 1-->4)-GlcNAc - most are sugar pentamers (but can range from 3-6 residues) - species specificity is due to variation in polymer length and potential substitution sites at the nonreducing end (R1 to R5) and two sites at the reducing end (R6 and R7) > R1 on the C-2 nitrogen is a fatty acid, usually 18-carbons long

Artificial sweeteners

- not carbohydrates - man-made - non-nutritive (no calories) - don't promote tooth decay - safe for diabetes a) saccharin - diet soft drinks ("Sweet & Low") - banned from 1977-1991 because it showed risk of bladder cancer in rats (shown to have no correlation in humans) b) aspartame ("Nutrasweet," "Equal") - variety of food + drink; mostly widely used artificial sweetener - peptide of 2 amino acids (aspartate + phenylalanine) - 4 cal/g - 180x sweeter than sugar; very little needed - ADI (acceptable daily intake) = 50 mg/kg - should not consume during pregnancy - very very dangerous for people with phenylketonuria (PKU), who can't metabolize phenylalanine (all products containing aspartame c) sucralose ("splenda") - no calories (not broken down or absorbed) - chlorinated sucrose - 600x sweeter than sucrose - safe for diabetics - heat-stable (can use in cooking & baking) - shown to be safe d) acesulfame potassium ("Sunette," "Sweet One") - nearly as sweet as aspartame (act sunergistically) - chewing gums, beverages, instant tea & coffee, puddings, gelatin e) neotame (called "super aspartame") - (7k-13k)x sweeter than sucrose - in processed food; not for home use - also has phenylalanine, but is not digestible (so it's safe for people with PKU) f) tagatose - derived from lactose - 80% remains unabsorbed - high doses cause flatulence, cramping, loose stool

Insoluble fibers

- not dissolved in water - form structural part of plant cell - cellulose, hemicellulose, lignins - seeds, whole grains

Carbohydrate basic nomenclature

- number of carbon atoms + -ose ex) 3 carbons = triose

How do oligosaccharides determine glycoprotein structure?

- oligosaccharides are usually attached at loops or turns - flexible groups that can, over time, occupy a large volume - oligosaccharides can shield a protein's surface, modifying its activity or protecting it from proteolysis - they may play a structural role, by limiting the conformational freedom of the attached protein - N-linked oligosaccharides are added as proteins are being made (and thus can help to determine how the protein folds) > they might stabilize the folded conformation of the protein by reducing backbone flexibility - O-linked oligosaccharides cluster is heavily glycosylated segments of the protein, and may stiffen or extend the protein chain

What is the role of oligosaccharides in mediating recognition?

- oligosaccharides with unique structures are components of a variety of glycoproteins or glycolipids on the outer surface of the plasma membranes ex) the oligosaccharide moieties are bound by extracellular lectins with high specificity and affinity

GlcNAc - a nutrient sensor

- one of the most common post-translational modifications of proteins is the addition of a single N-acetyl-glucosamine (GlcNAc) to Ser or Thr residues in cytoplasmic, nuclear, or mitochondiral proteins

Peptidoglycan sheets

- peptide chains and pentaglycine bridges hold several polysaccharide chains together - this forms a sheet of peptidoglycan > several sheets can be stacked to thicken the peptidoglycan layer

#3: Hypertension

- perhaps more so than sodium - people who get ~25% of daily calories from sugar are 3x likely to die from cardiovascular disease than those who only get 10% (likely due to excess calories, weight gain)

Give an example of a bacteria biofilm

- plaque on the surface of teeth - allows bacteria to adhere to tooth - creates a barrier to antimicrobial agents

What is the role of the carbohydrates attached to glycoproteins?

- play role in protein-protein recognition

Glypicans

- protein is anchored to a lipid membranes

What is aggrecan?

- proteoglycan complex found in cartilage - attached to the central winding hyaluronic acid chain are core proteins, which extend up and down - link proteins attached the core proteins to the hyaluronic acid chain - GAG = glycosaminoglycan chains

Cyclohexane rings: chair vs boat conformations

- pyranose rings favor chair conformations - multiple chair conformations are possible but require energy for interconversion (~46 kJ/mol) - the boat conformation is only seen in derivatives with very bulky substituents

Agaropectin

- repeating disaccharide of D-galactose-(Beta 1-->4)-3,6-anhydro-L-galactose (same as agarose) - has sulfate ester side chains and D-glucuronic acid

Glycoconjugate #3: Glycoproteins

- root word is protein, so glycoproteins are mostly protein - they're oligosaccharides attached to protein > oligosaccharides vary from 1-30 sugar residues > the carbohydrate is attached via its anomeric carbon to amino acids on the protein - includes some enzymes, hormones, structural proteins, transport proteins, and antibodies - oligosaccharide is added to protein in Golgi complex - if the glycosylated protein is found in the membrane, the oligosaccharide is usually on the extracellular side - oligosaccharides are often recognized by the immune system

What is an isomer?

- same molecular formula, different structures

What are SCFAs? What do they do?

- short chain fatty acids - affect how our cells absorb electrolytes - protect against colorectal cancer - may help protect against C. difficile bacterial diarrhea

Monosaccharides

- simple sugars (glucose, fructose, galactose) - trioses

#2: Constipation, diarrhea, hemorrhoids

- softens stool - aids is passage of stool - some fibers harden watery stool

How can soluble fiber lower cholesterol?

- soluble fiber can be absorbed through intestinal epithelium into lymph - can bind to fat and prevent fat absorption into the body, lowering cholesterol

Explain why people with blood type O have a several-fold higher incidence of gastric ulcers than types A and B

- some bacteria adhere to and colonize/infect animal cells - they recognize the oligosaccharide Lewis b, which is present in glycoproteins and glycolipids that define type O blood group

Infants with lactose intolerance are given what?

- soy formula

Diastereomers

- stereoisomers that are not mirror images - have different physical properties (water solubility, melting temp) - epimers + anomers

Hemoglobin glycation - AGEs

- subsequent reactions to already glycated hemoglobin yield a mixture of advanced glycation end products (AGEs) - AGEs leave erythrocytes and form covalent cross-links with proteins, interfering with normal protein function - high concentrations of AGEs can cause damage to the kidneys, retina, and cardiovascular system - interact with transmembrane receptors, trigger characteristic inflammatory responses associated with diabetes

Epimers

- subtype of diastereomers (stereoisomers that are NOT mirror images) that differ in absolute configuration at exactly one chiral carbon - epimers

Anomers

- subtype of epimers that differ at the anomeric carbon

#4: Behavior

- sugar = hyperactivity --> UNPROVEN - may indirectly affect children via poor nutrition (sugar replaces other nutrients)

Glycoconjugates - definition and four major types

- sugar chains/molecules attached to other molecules 1) Proteoglycans 2) Peptidoglycans 3) Glycoproteins 4) Glycolipids

#5: Dental caries (cavities)

- sugars support bacterial growth - leads to plaque (also acid produced during fermentation eats away at tooth enamel) - if >10% total cals come from sugar, increases incidence of caries Other factors: 1. amount of time sugar/starch stays in mouth (to prevent, brush teeth, rinse w/ water, chew sugarless gum ... bacteria action is maximal within 20 minutes of first contact) 2. stickiness of food - how strongly it sticks to teeth (honey, syrup) Caries prevention: - low sugar/sugarless food - saliva helps to kill bacteria, neutralize mouth - fluoride protects and strengthens teeth - cheese, raw veggies prevent carries - coffee, tea, beer chocolate (tannin)

What does the synthesis of GAGs require?

- synthesis of glycosaminoglycans requires: 1) enzymes that activate monomeric sugars 2) transportation of the monomeric sugars across membranes 3) condensation of the activated sugars into polysaccharides 4) the addition of sulfates

sugar alcohols

- the carbonyl carbon is reduced to an alcohol - every carbon has a hydroxyl --> in image from left to right: glycerol, myo-inositol, D-ribitol ex) glycerol (triacylglycerols & glycerophospholipids) ex) inositol (phosphatidylinositol, inositol triphosphate (IP3)) --> these are used as alternative sweeteners

For reducing disaccharides: Compare the stability of the glycosidic bond to the stability of the unreacted monomer.

- the glycosidic bond (which is an acetal) between monomers is more stable and less reactive than the hemiacetal on the unreacted monomer - when two monomers react, an acetal is formed between them, but the second monomer is left with a hemiacetal on the far right of the ring - the second monomer (with the hemiacetal) is reducing, whereas the anomeric carbon involved in the glycosidic linkage is nonreducing

How are oligosaccharides used to transfer lysosomal enzymes into the lysozyme?

- the mannose 6-phosphate receptor/lectin of the trans Golgi complex binds to the oligosaccharide of the lysosomal enzymes - this targets those enzymes for transfer into the lysosome - in short - oligosaccharides are needed for helping proteins reach their final destination

What is I-cell disease (mucolipidosis II)?

- there's normally a carbohydrate tag on digestive enzymes that directs them from the golgi to the lysosomes > these tags normally consist of mannose-6-phosphate - people with I-cell disease lack these tags > these people are deficient for a phosphotransferase > therefore a phosphate group is not added to mannose - the enzymes that were meant to end up in lysosomes are exported into blood and urine - consequently the lysosomes accumulate large "inclusions" (I) of undigested glycolipids and glycosaminoglycans - these patients experience psychomotor retardation and skeletal deformities

Disordered eating - low-carb dieters

- these diets tend to be high in fat and saturated fat > raises LDL ("bad cholesterol") levels significantly > raises total cholesterol > may have pro-arrhythmic effect on heart muscle - excludes many fruits and veggies > can become deficient in vitamins and minerals (esp iron, calcium, magnesium, thiamine)

Type 1 disbetes

- these individuals cannot lower blood sugar (hyperglycemia) - can lead to kidney failure, cardiovascular disease, blindness, and impaired wound healing - insulin injections needed to keep BG levels near normal - BG checked with portable glucose monitor - done to assess how much glucose to inject - portable glucose sensors use electrochemical detection

The peptides that are attached to each NAM are also covalently linked to each other (in other words, two peptides are connected). What are the two possible ways they can be connected?

- they are either: 1) directly connected together (common in gram-neg bacteria like E. coli) 2) linked via a pentaglycine peptide bridge (common in gram-positive bacteria like staphylococcus aureus)

What is the binding specificity of lectins?

- they are highly specific to the correct carbohydrate binding partner - in a cluster of oligosaccharides on a cell surface, each one can engage one of the lectin's carbohydrate-binding domains (CBDs) > polar groups interact via hydrogen bonds > less polar groups interact with non-polar amino acid side chains

What are lectins?

- they are proteins that contain two or more binding sites for carbohydrates - they facilitate cell-cell contact

Where are sulfated glycosaminoglycans (GAGs) located?

- they attach to a large rod-shaped protein in the cell membrane > interact with a variety of receptors from neighboring cells and regulate cell growth

Compare the "reducing end" to "non-reducing end" ratio of glycogen and amylopectin

- they both have one reducing end but both have many nonreducing ends (because have lots of branches, which have nonreducing ends) - enzymatic processing occurs simultaneously on many nonreducing ends - this is why having branches makes the homopolymers easier to break down ..... - since glycogen has far more branchpoints, it is more quickly broken down than amylopectin

What are granules?

- they contain enzymes that synthesize and degrade the polymers (starch and glycogen)

What causes tomatoes to soften?

- they get their firmness from pectin - when the enzyme polygalacturonase is made, the pectin is broken down, and the tomato becomes soft

How were GMOs used to preserve tomatoes from ripening?

- they introduced tomato DNA that disrupted the polygalacturonase gene - this caused less of the enzyme to be secreted, which prevented pectin from being broken down

What role do glucosinolates play in humans?

- they stimulate the production of detoxifying enzymes that play a role in cancer prevention

Explain how the sweetness of artificial sweeteners is detected

- they're hundreds of times sweeter than sucrose - they bind only to Tas1R2, whereas natural sugars bind to 3 binding sites on the receptor: 1) AH+ - contains an alcohol or amine that hydrogen bonds to partial neg charge on sweetener 2) B- - has a partial neg oxygen that hydrogen bonds with partial positive group on sweetener 3) X - perpendicular to other groups - interacts with a hydrophobic patch on sweetener

Sugar acids from glucose - Alduronic acid Ex) (GlcUA) D-Glucuronic acid AKA D-Glucuronate

- to get D-Glucuronate, oxidize C6 of glucose

What is the glycosidic bond?

- two sugar molecules (monosacchaides) can be joined via a glycosidic bond - these bonds can be α or β

Nonreducing disaccharides

- two sugar molecules are joined via a glycosidic bond between two anomeric carbons (AKA between two hemiacetals) - the product has two acetal groups and no hemiacetals - since there are no reducing ends, this is a nonreducing sugar

Carb content: - fruit

- typical fruit serving provides 15 g carbs > mostly sugars > vary in starch and fiber content - up to 2 g fiber/serving - 1/2 cup berries, 1 med apple, orange, banana

Amylose

- unbranched polymer of (α 1-->4) linked residues - linear polymer [Glucose-(α 1-->4)-glucose] - 100-1000 glucose residues - can assume a left-handed helical conformation - helix can trap iodine (turns blue/purple)

O-antigens

- unique to each strain of bacterium - recognized by the immune system - often contains some unusual sugars

What is chitosan?

- water-soluble enzymatically processed chitin - made from environmental wastes, such as shells from marine crustaceans - has a variety of uses: > carrier to assist drug delivery > surgical stiches > component of skin, hair, and oral care products > stabilizing and thickening component of feed products > adhesive used in surgical dressings

How much dietary fiber is needed a day?

- while it is indigestible and has zero calories, it is recommended to consume 20-35 g/day

Ruminants (cow, sheep) and termites live symbiotically with what?

- with microorganisms that produce cellulase - this allows them to absorb the glucose freed from cellulose into their blood streams

How quickly are carbohydrates absrobed?

- within 3-4 hours after a meal

What do amylases do?

- α-Amylase cleaves random internal (α 1-->4) glucosidic bonds - β-Amylase acts on nonreducing ends; generates maltoses - salivary glands and pancrease secrete mixtures of alpha and beta amylases

What are β-glucans?

- β-glucans are found in a variety of organisms (bacteria, yeast, fungi, cereal grains) - most have glucose-(β 1-->3)-glucose - some may have (α 1-->6) branch points - cereal grains (oat & barley) alternate (β 1-->3) and (β 1-->4) branch points

Targeting Peptidoglycan: Defense

--> since the cell wall is both essential and unique to bacteria, it is perfect to target 1. penicillin - antibiotic from Penicillium fungus > has β-lactam ring that structurally resembles terminal D-Alanine (D-Alanyl-D-Alanine) in the peptide bridge found in peptidoglycan > interferes with cell wall synthesis by irreversibly inhibiting the enzymes that catalyze the transpeptidation of peptidoglycan (prevents crosslinking of peptidoglycan strands) - therefore cell wall synthesis is blocked - cell bursts due to osmotic pressure > only effective against actively growing cells 2. lysozyme - enzyme produced by mammals that cleaves bonds between GlcNAc & MurNAc (NAG & NAM) > antibacterial > found in mucus, saliva, tears, sweat, breast milk

How to assess long-term BG levels: Hemoglobin A1C

1. a sample of blood is attained 2. hemoglobin is obtained and the glycated hemoglobin (GHB) is separated from unmodified hemoglobin (using the charge difference of the amino groups) --> normal values of monoglycated hemoglobin (HbA1C) is about 5% of the total hemoglobin --> this value corresponds to a glucose level of 120mg/100mL - in untreated diabetes, this value may be as high as 13%, which represents a glucose level of 300mg/100mL - successful insulin therapy = keeping HbA1C at 7%

What are the two families of sphingolipids?

1. cerebrosides - single monosaccharides attached to a ceramide 2. gangliosides - oligosaccharide containing sialic acid attached to ceramide > in vertebrates, ganglioside carbohydrate composition determines blood groups (as antigens)

What are the four types of protein interactions with NS (highly sulfated) domains of heparan sulfate?

1. conformation activation - conformational change induced in the protein antithrombin (AT) - this change allows its interaction with blood clotting factor Xa, preventing clotting 2. enhanced protein-protein interaction - the binding of antithrombin (AT) and thrombin to two adjacent NS domains bring the two proteins into close proximity, favoring their interaction, which inhibits blood clotting 3. coreceptor for extracellular ligands - the NS domains of HS interact with both the fibroblast growth factor (FGF) and its receptor, bringing the oligomeric complex together and increasing the effectiveness of a low concentration of FGF 4. cell surface localization/concentration effect - the high density of negative charges in heparan sulfate attracts positively-charged lipoprotein lipase molecules and holds them by electrostatic and sequence-specific interactions with NS domains (holds them, cleaves circulating lipoproteins for fat storage)

In what ways can oligosaccharides have variety?

1. differences in total number of sugars in oligosaccharide (usually 1-30) 2. they can contain several different sugars in different sequences (there are 8 predominant sugars) 3. the sugars can be joined by either alpha or beta linkages 4. linkages can join different carbons 5. either O- or N- linked to protein 6. can contain up to 4 branches > variety depends on which glycosyltransferase enzymes are present in any given cell (sugars are NOT coded for by genes; what are encoded for are enzymes!)

How is red meat associated with cancer?

1. nitrates used to preserve red color 2. red meat contains high levels of a sugar called Neu5Gc (N- glycolylneuraminic acid) > eating red meat could cause the production of antibodies against the sugar, meaning that each time it's eaten it causes chronic inflammation, which is a known contributor to cancer --> moderate red meat intake has health benefits (iron, protein, vit B12

Cyclization of Ribose

1. nucleophilic alcohol (hydroxyl on C4) attacks the electrophilic carbonyl carbon (C1), allowing formation of a hemiacetal - result: linear carbohydrate forms a ring structure 2. the carbonyl carbon is reduced to an alcohol - the orientation of the alcohol around the carbon is variable and transient - the carbonyl carbon becomes a new chiral center (called the anomeric carbon)

Cyclization of Glucose

1. nucleophilic alcohol (hydroxyl on C5) attacks the electrophilic carbonyl carbon (C1), allowing formation of a hemiacetal - result: linear carbohydrate forms a ring structure 2. the carbonyl carbon is reduced to an alcohol - the orientation of the alcohol around the carbon is variable and transient - the carbonyl carbon becomes a new chiral center (called the anomeric carbon) - all hydroxyl groups on the RIGHT in the Fischer projection end up DOWN in the ring - LEFT in the Fischer turn out UP in the ring

Two types of alternative sweeteners

1. nutritive 2. artificial

What are the roles of teichoic acids?

1. regulate cell wall synthesis 2. involved in uptake of Mg2+ ions

What are the two types of teichoic acids?

1. wall teichoic acid - attached to peptidoglycan 2. lipoteichoic acid - attached to glycolipids in cell membrane (keeps cell wall attached to cell membrane)

7 Health effects of fiber

1. weight control 2. prevents constipation, diarrhea, hemorrhoids 3. prevents appendicitis 4. prevents diverticulosis 5. prevents colon cancer 6. prevents heart disease 7. helps to manage diabetes

Give some examples of oligosaccharides mediating recognition

ex) lectins lie on cell surfaces and recognize specific carbohydrates on cell surfaces > they recognize individual monosaccharides in particular linkages > this involves extensive hydrogen bonding and van der waals packing ex) proteins on sperm surfaces recognize GlcNAc or Gal residues on glycoproteins on the ovum during fertilization ex) viruses, bacterium, and parasites invade their target tissues by first binding to cell surface carbohydrates ex) bacterial toxins, such as the cholera and pertussis toxins, bind to a surface glycolipid before entering a cell

Sugar alcohols as alternative sweeteners

ex) maltitol, xylitol, sorbitol, mannitol - end in suffix -itol - occur naturally in fruits - 2-3 cal/g (normal sugar has 4 cal/g) - sugar free gum, baked goods - pros: metabolized slower than sugar, fewer cavities - cons: fermented by intestinal bacteria --> gas - discomfort + diarrhea

When aldehydes are attacked by alcohols, what is formed?

hemiacetals

When ketones are attacked by alcohols, what is formed?

hemiketals

Heparan sulfate structure

heparin-like polysaccharide but attached to proteins Structure: NA = N-acetylated domains NS = highly sulfated domains

Many ____ in living organisms are D stereoisomers

hexoses