Carbohydrates. Prof. Ramune Morkuniene

Transcription

1 Carbohydrates Prof. Ramune Morkuniene

2 Topics Monosaccharides and their derivatives Disaccharides. Lactose intolerance Carbohydrate sweeteners. Artificial sweeteners Blood type and monosaccharides

3 Important Simple Monosaccharides 1. Glucose 2. Mannose 3. Galactose 4. Fructose 5. Ribose

4 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.

5 Sugar derivatives: Deoxysugar L-Fucose (6-deoxy-Lgalactose): Important in immune recognition

6 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

7 N-acetylneuraminate (sialic acid) N-acetylneuraminate, (N-acetylneuraminic acid, 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.

8 Influenza Virus Binds to Sialic Acid 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.

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10 Glucosaminoglycans 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.

11 Cartilage: glycosaminoglycans branches

12 Normal blood glucose concentration: mm Hyperglycemia Non-enzymatic glycosylation of proteins

13 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.

14 Increased blood glucose and hemoglobin: formation of glycosylated hemoglobin Hemoglobin, in your blood, joins up with glucose to form the chemical called HbA1c

15 HbA1c Formation of a covalent linkage between glucose and the NH 2 terminal amino acid of the hemoglobin β chain: the Amadori reaction

16 Monitoring of HbA 1c levels More glycosylated hemoglobin More glucose Uncontrolled diabetes It is important to monitor HbA 1c levels in all diabetic patents. The monitoring of HbA 1c is an indication of insulin adherence. 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.

17 Glycosylation of Collagen: contribution to atherogenesis

18 Atherogenesis

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20 Disaccharides A disaccharide consists of two monosaccharides. Disaccharide Maltose + H 2 O Lactose + H 2 O Sucrose + H 2 O Monosaccharides Glucose + Glucose Glucose + Galactose Glucose + Fructose

21 Hydrolysis of lactose: lactase action

22 Lactose intolerance Lactose intolerance is the loss of lactase activity in the small intestine Sucrase, lactase, and maltase are located on the outer surface of epithelial cells lining the small intestine.

23 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.

24 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.

25 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. In white Americans and northern Europeans In Mexican Americans In black South Africans In Chinese and Japanese In Mestizos and Peru Age 2-3 yrs. Age 6 yrs. Age 9-10 yrs. 6% 6% 15% 18% 30% 47% 25% 45% 60% 30% 80% 85% 30 55% 90% >90%

26 Lactose intolerance

27 Sucrose: Is the disaccharide known as table sugar. Sucrose

28 Carbohydrate sweeteners All carbohydrate sweeteners sugar, honey, juice concentrates contain primarily sugars and enhance taste and enjoyment of a variety of foods.

29 RELATIVE SWEETNESS OF DIFFERENT SUGARS Sucrose 100 Glucose 74 Fructose 174 Lactose 16 Maltose 32 Galactose 32 Standart

30 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

31 Sweetness of Sweeteners Sugars and artificial sweeteners differ in sweetness.

32 Discovery of Non-Carbohydrate Sweeteners Saccharin: Saccharin was discovered in 1879 by C. Fahlberg. While working in the lab, he spilled a chemical on his hand. Later while eating dinner, Fahlberg noticed a more sweetness in the 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.

33 Saccharin and bladder cancer 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.

34 Aspartame: In 1965, Jim Schlatter, a chemist was working on a project to discover new treatments for gastric ulcers. One of the steps in the research process was to make a dipeptide intermediate, aspartylphenylalanine methyl ester. He accidently spilled some on his hand. Later he licked his finger and noticed the sweet taste. The result was the sweetner, aspartame.

35 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.

36 Sucralose: 600 Substituting three chlorine ions for hydroxyl groups on sucrose molecule makes Sucralose. Sucralose may have the strangest "accidental discovery" story. Tate & Lyle, a British sugar company, was looking for ways to use sucrose as a chemical intermediate. Halogenated sugars were being synthesized 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 chlorinated sugars.

37 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 glycosyltransferases. Each person inherits the gene for one glycosyltransferase of this type from each parent.

38 ABO blood groups O (I) A (II) B (III) AB (IV)

39 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.

40 ABO blood groups Recipient Donor O (I) O A (II) A or O B (III) B or O AB (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 the universal recipient. Individuals of type A, B, AB and O blood can receive blood from donors of type O blood. Type O blood is called the universal donor.

41 Blood group inheritance