Carbohydrates

Prof. Ramune Morkuniene

Topics

• Monosaccharides and their derivatives• Disaccharides. Lactose intolerance• Carbohydrate sweeteners. Artificial

sweeteners• Blood type and monosaccharides

Important Simple Monosaccharides

1. Glucose2. Mannose3. Galactose4. Fructose5. Ribose

Sugar derivatives

• Carbohydrates can be modified by substituents other than hydroxyl groups.– Amino sugars– Deoxysugars

• These are important components of glycoconjugates

• Expressed on cell surfaces functioning in cellular recognition and identity.

Sugar derivatives: DeoxysugarL-Fucose (6-deoxy-L-

galactose):Important in immune recognition

Sugar derivatives: Amino sugar

• Amino sugar - an amino group substitutes for one of the hydroxyls. An example is glucosamine.

• The amino group may be acetylated.– N-acetylglucosamine– N-acetylgalactosamine

N-acetylneuraminate (sialicacid)

• N-acetylneuraminate, (N-acetylneuraminicacid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins.

• Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH, as shown here.

Influenza Virus Binds to SialicAcid Residues

• The ability of viruses to infect specific cell types is the ability of these viruses to bind to particular structures or receptors on the surfaces of cells. For example, influenza virus recognizes sialic acid residues present on cell-surface glycoproteins.

• After these surface interactions have taken place and the virus has been taken into the cell, another viral protein, neuramidase, cleaves the glycosidic bonds to the sialic acid residues, freeing the virus to infect the cell.

• Inhibitors of neuramidase enzyme are as anti-influenza agents.

• Chondroitin sulfate,• Keratan sulfate, • Heparin, • Heparan sulfate, • Dermatan sulfate

• Many glycosaminoglycans are made of disaccharide repeating units containing a derivative of an amino sugar, either glucosamine or galactosamine. Is present on the animal cell surface and in the extracellular matrix.

• Glycosaminoglycans are usually attached to proteins to form proteoglycans.

Glucosaminoglycans

Cartilage: glycosaminoglycansbranches

Normal blood glucose concentration:

• 3.3 -5.5 mM

Hyperglycemia

Non-enzymatic glycosylation of proteins

Glucose is linked with free amino group or to the N-terminal amino group of protein: the Amadori reaction

• The Amadori rearrangement is an organic reaction describing the acid or base catalyzed isomerization or rearrangement reaction of the N-glycoside of an aldose to the corresponding ketose.

Increased blood glucose and hemoglobin: formation of glycosylated hemoglobin

Hemoglobin, in your blood, joins up with glucose to form the chemical called HbA1c

Formation of a covalent linkage between glucose and the NH2 terminal amino acid of the hemoglobin βchain: the Amadori reaction

HbA1c

Monitoring of HbA1c levels

It is important to monitor HbA1c levels in all diabetic patents. The monitoring of HbA1c is an indication of insulin adherence.

• More glycosylatedhemoglobin

• Uncontrolled diabetes

• More glucose

• Red cells live for 8 -12 weeks before they are replaced. By measuring the HbA1C it can tell you how high your blood glucose has been on average over the last 8-12 weeks.

Glycosylation of Collagen:contribution to atherogenesis

Atherogenesis

Disaccharides

A disaccharide consists of two monosaccharides.

Disaccharide Monosaccharides• Maltose + H2O Glucose + Glucose• Lactose + H2O Glucose + Galactose• Sucrose + H2O Glucose + Fructose

Hydrolysis of lactose: lactaseaction

Sucrase, lactase, and maltase are located on the outer surface ofepithelial cells lining the small intestine.

Lactose intolerance is the loss oflactase activity in the small intestine

Lactose intolerance

Diagnosis of lactose intolerance

• Symptoms: nausea, cramps, bloating, gas, and diarrhea

• Clinical symptoms typically appear within 30 minutes but may take up to 1-2 hours depending on other foods and activities.

Types of lactose intolerance• Congenital lactase deficiency. A genetic disorder

which prevents enzymatic production of lactase. Present at birth, and diagnosed in early infancy.

• Primary lactose intolerance. Environmentally induced when weaning a child in non dairy consuming societies. This is found in many Asian and African cultures, where commercial dairy products are uncommon.

• Secondary lactose intolerance. Environmentally induced, resulting from certain gastrointestinal diseases. A very common cause of temporary lactose intolerance is gastroenteritis, particularly when the gastroenteritis is caused by rotavirus.

Lactose intolerance• Lactose intolerance levels also increase with

age. European population that develops lactose intolerance, the development of lactose intolerance is a gradual process spread out over as many as 20 years.

Age 2 - 3 yrs. Age 6 yrs. Age 9 - 10 yrs.

In white Americans and northern Europeans

6% 6% 15%

In Mexican Americans

18% 30% 47%

In black South Africans

25% 45% 60%

In Chinese and Japanese

30% 80% 85%

In Mestizos and Peru 30–55% 90% >90%

Lactose intolerance

Sucrose

Sucrose:• Is the disaccharide

known as table sugar.

Carbohydrate sweeteners• All carbohydrate sweeteners

–sugar, –honey, –juice concentratescontain primarily sugars andenhance taste and enjoyment ofa variety of foods.

RELATIVE SWEETNESS OF DIFFERENT SUGARS

Sucrose 100

Glucose 74

Fructose 174

Lactose 16

Maltose 32

Galactose 32

Standart

Artificial Sweeteners: Noncarbohydrates

• Sweeteners are used in products such as nonalcoholic beverages, chewing gum, frozen dairy desserts, fruit juices and gelatins.

• Use of artificial sweeteners: –People with diabetes –People on a weight-loss diet

Sweetness of Sweeteners• Sugars and artificial sweeteners differ

in sweetness.

Discovery of Non-CarbohydrateSweeteners

Saccharin: 45000• Saccharin was discovered in 1879 by C. Fahlberg. While

working in the lab, he spilled a chemical on his hand. Laterwhile eating dinner, Fahlberg noticed a more sweetness inthe bread he was eating. He traced the sweetness back to the chemical, later named saccharin.

• It is not metabolized, therefore noncaloric sweetener.• By 1907, saccharin was used as a replacement for sugar

in foods for diabetics. • By the 1960s it was used on a massive scale in the "diet"

soft drink industry.

• Findings from animal studies indicated that sodium saccharin can cause bladder cancer.

• However, studies on people haven't shown any link between bladder cancer risk and saccharin intake – it was concluded that saccharin is safe to ingest.

• In 2000, saccharin was delisted from a national report of carcinogens.

Saccharin and bladder cancer

Aspartame:18000

• In 1965, Jim Schlatter, a chemist was working ona project to discover new treatments for gastriculcers. One of the steps in the research processwas to make a dipeptide intermediate, aspartyl-phenylalanine methyl ester. He accidently spilledsome on his hand. Later he licked his finger andnoticed the sweet taste. The result was thesweetner, aspartame.

• The body breaks down aspartame into aspartic acid and phenylalanine with a small amount of methanol:

• Methanol is metabolized to formaldehyde and formic acid. Formaldehyde is classified by the World Health Organization as a probable human carcinogen and is the major source of controversy over aspartame's safety.

• Aspartame was approved in 1981.

Sucralose:600

• Substituting three chlorine ions for hydroxyl groups onsucrose molecule makes Sucralose.

• Sucralose may have the strangest "accidentaldiscovery" story. Tate & Lyle, a British sugar company, was looking for ways to use sucrose as a chemicalintermediate. Halogenated sugars were beingsynthesized and tested. A foreign graduate student, Shashikant Phadnis, misunderstood a request for"testing" of a chlorinated sugar as a request for"tasting," leading to the discovery that many chlorinatedsugars.

Blood groups• O antigen• A antigen• B antigen• Carbohydrates are

attached on the surfaces of red blood cells.

• The human ABO blood groups illustrate the effects of glycosyl-transferases. Each person inherits the gene for one glycosyltransferase of this type from each parent.

ABO blood groups

O (I) A (II) B (III) AB (IV)

• These structures have important implications for blood transfusions and other transplantation procedures. If an antigen not normally present in a person is introduced, the person's immune system recognizes it as foreign. Adverse reactions can ensue, initiated by the intravascular destruction of the incompatible red blood cells.

ABO blood groupsRecipient DonorO (I) OA (II) A or OB (III) B or OAB (IV) A, B, AB, or

O• Individuals with of O blood can receive blood from donors of only type O. • Individuals with Type A blood can receive blood from donors of type A

and type O blood. • Individuals with type B blood can receive blood from donors of type B

and type O blood. • Individuals with type AB blood can receive blood from donors of type A,

type B, type AB, or type O blood. Type AB blood is referred to as theuniversal recipient.

• Individuals of type A, B, AB and O blood can receive blood from donorsof type O blood. Type O blood is called the universal donor.

Blood group inheritance