Biochemistry Lecture Notes PDF

BIOCHEMISTRY LEC Prof. Josh Macallang | First Semester BIOCHEMISTRY Cellulose It can be defined as the science concerned with the chemical Serves as structural elements. basis of life....

BIOCHEMISTRY LEC Prof. Josh Macallang | First Semester BIOCHEMISTRY Cellulose It can be defined as the science concerned with the chemical Serves as structural elements. basis of life. Starch It is the science concerned with the chemical constituents of living Provide energy reserves. cells and with the reactions and processes they undergo. A complete understanding of all chemical processes associated with living cells. FUNCTIONS OF CARBOHYDRATES The study of life at the molecular level. 1. Carbohydrate oxidation provides energy. SUBDIVISIONS OF BIOCHEMISTRY 2. Carbohydrate storage provides a short-term energy reserve. 1. Structural and Functional Biochemistry 3. Carbohydrates supply carbon atoms for the synthesis of other deals with the structure of each macromolecule and how they work biochemical substances individually and with the others. 4. Carbohydrates form part of the structural framework of DNA 2. Informational Biochemistry and RNA molecules. refers to the replication, transcription, and translation processes. 5. Carbohydrates linked to lipids are structural components of 3. Bioenergetics cell membranes deals with how our cells synthesize ATP (energy) from the nutrients 6. Carbohydrates linked to proteins function in a variety of we take in. cell–cell and cell–molecule recognition processes. MEDICAL BIOCHEMISTRY Diseases Associated With Disorders Of Carbohydrate Deals with the chemical basis of the human body. Metabolism CLINICAL BIOCHEMISTRY - Diabetes mellitus Deals with clinical diseases/pathological diseases of the human - Galactosemia body. - Glycogen storage diseases Fields examples are: Endocrinology, Immunology, Toxicology, - Lactose intolerance Forensic Medicine, Molecular biology, Medical instrumentation, etc. Simple Carbohydrates Use of Biochemical Investigations and Lab. Tests - Monosaccharides 1. Use: To reveal the fundamental causes and mechanisms - Disaccharides of diseases Complex Carbohydrates Example: Demonstration of the nature of the genetic - Oligosaccharides defects in cystic fibrosis. - Polysaccharides 2. Use: To suggest rational treatments of diseases based on CLASSIFICATION (No.1) above Monosaccharides Example: A diet low in phenylalanine for treatment of Simple sugar. phenylketonuria. Disaccharides 3. Use: To assist in the diagnosis of specific diseases 2 monosaccharide units. Example: Use of the plasma enzyme creatine kinase Mb Oligosaccharides (CK-MB) in the diagnosis of myocardial infarction. 3-10 monosaccharide units. 4. Use: To act as screening tests for the early diagnosis of Polysaccharides certain diseases More than 10 sugar units Example:Use of measurement of blood thyroxine for Homopolysaccharides thyroid-stimulating hormone (TSH) in the neonatal Heteropolysaccharides diagnosis of congenital hypothyroidism. 5. Use: To assist in monitoring the progress (e.g., recovery, worsening, remission, or relapse) of certain diseases Example: Use of the plasma enzyme alanine aminotransferase (ALT) in monitoring the progress of infectious hepatitis. 6. Use: To assist in assessing the response of disease to therapy. Example: Use of measurement of blood in carcinoembryonic antigen (CEA) in certain patients who have been treated for cancer of the colon. CARBOHYDRATES CHIRALITY: HANDEDNESS IN The most abundant organic molecules in earth MOLECULES The empiric formula is C(H2O)n, “hydrates of carbon” It is needed to understand carbohydrate chemistry. Carbohydrates are formed of carbon, hydrogen, and oxygen Molecules that possess “handedness” exist in two forms: a atoms with a ratio of 1:2:1 “left-handed” form and a “right-handed” form. It provide important part of energy in diet A left hand and a right hand are mirror images of each other Act as the storage form of energy in the body These are structural component of cell membranes |1  3. A carbon atom in a ring system, if not involved in multiple bonding, can be chiral centers. SIMPLE CARBOHYDRATES The smallest unit of saccharides is a monosaccharide. (“Mono” = one) CHIRALITY: MIRROR IMAGES Examples: Glucose and Fructose A mirror image is the reflection of an object in a mirror. Monosaccharides are also referred to as Simple Sugars. Objects can be divided into two classes on the basis of their ○ (C6H12O6) mirror images: ○ Glucose ○ Superimposable mirror images are images that ○ Fructose coincide at all points when the images are laid ○ Galactose upon each other. Further classified based on: ○ Nonsuperimposable mirror images are images 1. Number of carbon atoms where not all points coincide when the images 2. Functional sugar group: are laid upon each other. Aldehyde group - aldoses Keto group - ketoses CHIRALITY For organic and bioorganic compounds, the structural requirement for handedness is the presence of a carbon atom that has four different groups bonded to it in a tetrahedral Polyhydroxy aldehydes or ketones, or substances that yield orientation. these compounds on hydrolysis. The tetrahedral orientation requirement is met only if the bonds to the four different groups are all single bonds. A chiral center is an atom in a molecule that has four different groups bonded to it in a tetrahedral orientation. A chiral molecule is a molecule whose mirror images are not superimposable; have handedness An achiral molecule is a molecule whose mirror images are superimposable; do not possess handedness. CHIRAL Both can be written C3H6O3 or (CH2O)3 Empirical formula of many simpler carbohydrates: (CH2O)n (hence the name hydrate of carbon) Carbohydrate with an aldehyde group: Aldose Carbohydrate with a ketone group: Ketose ACHIRAL GUIDELINES FOR DETERMINING CHIRALITY 1. A carbon atom with multiple bonds is not a chiral center. 2. A carbon atom containing two or more similar substituents is not a chiral center. 2  DISACCHARIDE GROUPS ISOMERISM Structural Isomers: Compounds having same chemical formula but different structural formula Aldose Ketose TRIOSE Glyceraldehyde Dihydroxyacetone PENTOSE Ribose Ribulose STRUCTURE OF THE D-KETOSES HEXOSE Glucose Fructose ALDO-KETO ISOMERS Example: ○ GLUCOSE (Aldose) ○ FRUCTOSE (Ketose) 3  STEREOISOMERS Compounds with the same molecular formula, functional groups, and position of functional groups but with different conformations Enantiomers are stereoisomers whose molecules are nonsuperimposable mirror images of each other. Diastereomers are stereoisomers whose molecules are not mirror images of each other. Cis–trans isomers (of both the alkene and the cycloalkane types) are diastereomers. cis-trans isomers: with different conformation around double bonds ENANTIOMERS (D- and L-Forms) The term enantiomer comes from the Greek enantios, which means “opposite.” A dextrorotatory compound is achiral compound that rotates the plane of polarized light in a clockwise direction. A levorotatory compound is a chiral compound that rotates the plane of polarized light in a counterclockwise direction. If one member of an enantiomeric pair is dextrorotatory, then the other member must be levorotatory. Epimers CHO dimers that differ in configuration around only one specific carbon atom Glucose and galactose, C4 Glucose and Mannose, C2 Galactose and mannose are not epimers 4  One member of an enantiomeric pair will rotate a plane of The mirror images can’t be superimposed on each other, polarized light in a clockwise direction. It is said to be i.e. they are different dextrorotatory which is labeled (+) The mirror image isomers constitute an enantiomeric The other member of the pair will then rotate the light in a pair; one member of the pair is said to be the enantiomer counterclockwise direction. It is said to be levorotatory of the other. which is labeled (-) Structures that are mirror images of each other and are D & L designate absolute configuration of the designated as D- and L- sugars based on the position of asymmetric carbon atom farthest from the aldehyde or –OH group on the asymmetric carbon farthest from the ketone group carbonyl carbon Majority of sugars in humans are D-sugars D or L FORM α- and β-Forms Cyclization of Monosaccharides Monosaccharides with 5 or more carbon are predominantly found in the ring form ○ The aldehyde or ketone group reacts with the –OH group on the same sugar ○ Cyclization creates an anomeric carbon (former carbonyl carbon) generating the α and β configurations 5  MUTAROTATION In solution, the cyclic α and β anomers of a sugar are in equilibrium with each other, and can be interconverted spontaneously Mutarotation: Spontaneous conversion of one anomer to the other Galactose - part of lactose 1. Found in milk 2. Converts to glucose in the body Monosaccharides Glucose - dextrose or blood sugar 1. Primary fuel for the body 2. Found in all disaccharides and polysaccharides Ribose - component of ribonucleic acids (RNAs) and energy-rich compounds such as adenosine triphosphate (ATP) - An aldopentose Fructose – fruit sugar 1. Found in fruit, honey, syrup 2. Converts to glucose in the body 6  The "hotter" the final color of the reagent, the higher the concentration of reducing sugar; formation of brick red precipitate indicates a reaction with Benedict’s reagent. REACTIONS OF MONOSACCHARIDES OXIDATION USING WEAK OXIDIZING (TOLLEN'S REAGENT) It is a reaction that is used to distinguish aldehydes from ketones; give an aldonic acid Tollens' reagent, which is a mixture of silver nitrate and ammonia, oxidizes the aldehyde to a carboxylic acid With Tollens solution, glucose reduces Ag1 ion to Ag The formation of a dark grey precipitate or silver mirror on the bottom and sides of the test tube indicates a positive result, which means that the given sample contains REACTIONS OF MONOSACCHARIDES reducing sugars/ aldoses. OXIDATION USING WEAK OXIDIZING (Heat, Acidic KMnO4 or HNO3) Can oxidize both ends of a monosaccharide at the same time (the carbonyl group and the terminal primary alcohol group) to produce a dicarboxylic acid. Such polyhydroxy dicarboxylic acids are known as aldaric acids. For glucose, this oxidation produces glucaric acid. REACTIONS OF MONOSACCHARIDES OXIDATION USING ENZYMES Although it is difficult to do in the laboratory, in biochemical systems enzymes can oxidize the primary alcohol end of an aldose such as glucose, without oxidation of the REACTIONS OF MONOSACCHARIDES aldehyde group, to produce an alduronic acid. OXIDATION USING WEAK OXIDIZING For glucose, such an oxidation produces D-glucuronic (BENEDICT’S REAGENT) acid. It is a chemical test that can be used to check for the presence of reducing sugars Therefore, simple carbohydrates containing a free ketone or aldehyde functional group can be identified with this test. Benedict’s solution, glucose reduces Cu21 ion to Cu1 ion It is a complex mixture of sodium carbonate, sodium citrate, and copper(II) sulfate pentahydrate. 7  REACTIONS OF MONOSACCHARIDES FORMATION OF PHOSPHATE ESTER The hydroxyl groups of a monosaccharide can react with inorganic oxyacids to form inorganic esters Alkyl/Aryl Acid Phosphates are formed by the reaction of phosphoric anhydride (phosphoric pentoxide or P2O5) and an alcohol (ROH). Phosphate esters, formed from phosphoric acid and various monosaccharides, are commonly encountered in biochemical systems. REACTIONS OF MONOSACCHARIDES REACTIONS OF MONOSACCHARIDES REDUCTION TO PRODUCE SUGAR FORMATION OF AMINO SUGAR ALCOHOL If one of the hydroxyl groups of a monosaccharide is The carbonyl group in a monosaccharide can react with a replaced with an amino group, an amino sugar is reducing agent like hydrogen or sodium borohydride produced. (NaBH4) and is reduced to a hydroxyl group resulting to a In naturally occurring amino sugars, of which there are polyhydroxy alcohol called sugar alcohol or alditol. three common ones, the amino group replaces the carbon An example of a polyhydroxy alcohol is D- sorbitol / 2 hydroxyl group. D-glucitol, a popular sweetening agent; It is the reduction Amino sugars and their N-acetyl derivatives are important of D-glucose building blocks of polysaccharides found in chitin and hyaluronic acid. The N-acetyl derivatives of D-Glucosamine and D-galactosamine are present in the biochemical markers on red blood cells, which distinguish the various blood types REACTIONS OF MONOSACCHARIDES FORMATION OF GLYCOSIDE The hydroxyl group of the anomeric carbon in a cyclic structure of monosaccharide can react with another alcohol molecule via formation of a glycosidic bond The figure below shows the reaction between a-D-glucose and methanol (CH3OH) in the presence of an acid catalyst. The product is Methyl-a-D-glucoside. 8  DISACCHARIDES Maltose is a reducing because the glucose unit on the Monosaccharides combine together to form disaccharides right has a hemiacetal carbon atom (C-1) (“Di” = two) Joining of 2 monosaccharides by O-glycosidic bond: ○ Maltose (α-1, 4)= glucose + glucose ○ Sucrose (α-1,2) = glucose + fructose ○ Lactose (β-1,4) = glucose + galactose The most important chemical reaction of maltose is that of The bond that links the two monosaccharides of a hydrolysis. Hydrolysis of D-maltose, whether in a disaccharide (glycoside) together is called a glycosidic laboratory flask or in a living organism, produces two linkage. molecules of D-glucose. Many disaccharides contain both a hemiacetal carbon Acidic conditions or the enzyme maltase is needed for the atom and an acetal carbon atom, as is the case for the hydrolysis to occur. preceding disaccharide structure. Hemiacetal and acetal HYDROLYSIS locations within disaccharides play an important role in the chemistry of these substances. It is normally formed between the carbon-1 of one monosaccharide and carbon-4 of the other monosaccharide. The formation of glycosidic bonds involves the condensation of water molecules. In a disaccharide, the two monosaccharide units are joined by an ether linkage. Maltose - malt sugar 1. Glucose + Glucose 2. Found in germinating seeds & used in fermentation to produce malted beverages (beer, whiskey) Malt (germinated barley that has been baked and ground) CELLOBIOSE contains maltose; hence the name malt sugar 1. Glucose + Glucose 2. Produced as an intermediate in the hydrolysis of the polysaccharide cellulose Like maltose, cellobiose contains two D-glucose monosaccharide units. It differs from maltose in that one of the D-glucose units—the one functioning as a hemiacetal—must have a b configuration instead of the a configuration for maltose; resulting to a b(1 → 4) CONDENSATION glycosidic linkage 9  Like maltose, cellobiose is a reducing sugar, has three lactose-free diet for 3-4 weeks could give you the isomeric forms in aqueous solution, and upon hydrolysis answers you want without expensive tests. produces two D-glucose molecules 2. Standard Lactose Tolerance Test Despite these similarities, maltose and cellobiose have - Blood glucose levels are measured before, at 30 different biochemical behaviors. These differences are minutes, and at 60 minutes after consuming 50g related to the stereochemistry of their glycosidic linkages. of lactose. Your blood will then be analyzed for Maltase, the enzyme that breaks the glucose–glucose lactose malabsorption. Malabsorption is also a(1→4) linkage present in maltose, is found both in the correlated to symptoms such as abdominal human body and in yeast. Consequently, maltose is bloating, discomfort diarrhea, and gas. digested easily by humans and is readily fermented by 3. Lactose Hydrogen Breath Test yeast. - After consuming 25-50g of a lactose liquid, Both the human body and yeast lack the enzyme breath samples are taken every 30 minutes for cellobiase needed to break the glucose glucose b(1 →4) up to 3 hours. A rise in breath hydrogen indicates linkage of cellobiose. Thus, cellobiose cannot be malabsorption of lactose (an increase in digested by humans or fermented by yeast. hydrogen is caused by fermentation of sugar by your gut flora). NOTE! Approximately 25% of patients will have a false negative breath test. Lactose - milk sugar Sucrose - table sugar 1. Glucose + Galactose 1. Glucose + Fructose 2. Lactose intolerance missing digestive enzymes 2. Refined from sugar beets and cane needed to split into two monosaccharide parts to It is the most abundant of all disaccharides absorb it. Souring of milk is caused by the conversion of lactose to lactic acid by bacteria in the milk. Sucrose, unlike maltose, cellobiose, and lactose, is a nonreducing sugar. In sucrose, the hemiacetal center (anomeric carbon atom) of each monosaccharide is involved in the glycosidic linkage. The result is a molecule that contains two acetal centers. Sucrose, in the solid state and in solution, exists in only Lactose can be hydrolyzed by acid or by the enzyme one form—there are no a and b isomers, and an lactase, forming an equimolar mixture of galactose and open-chain form is not possible. glucose Genetic condition lactose intolerance, an inability of the human digestive system to hydrolyze lactose. Sucrase, the enzyme needed to break the a, b(1→2) linkage in sucrose, is present in the human body. Hence LACTOSE INTOLERANCE TESTS sucrose is an easily digested substance. Sucrose 1. Elimination DIY Test hydrolysis (digestion) produces an equimolar mixture of - Try a lactose-free diet; this is as simple as it glucose and fructose called invert sugar sounds. If you suffer from clinical symptoms (like abdominal cramps and diarrhea), sticking to a 10  stomach and small intestine. In the large intestine, they are fermented by bacteria that do possess the α-GAL enzyme and make short-chain fatty acids. OTHER TYPES OF GLYCOSIDIC LINKAGES Three of the four disaccharides considered in this section - maltose, cellobiose, and lactose- have (1 to 4) glycosidic linkages. The other disaccharide considered, sucrose, has a (1 to 2) glycosidic linkage. Other carbon atoms besides 1, 2, and 4 can also participate in glycosidic linkages. An additional common type of glycosidic linkage is one that involves carbons 1 and 6. Several disaccharides not derailed in this section have α (1 to 6) glycosidic linkages. The following structure is for two α-D-glucose molecules connected via an α (1 to 6) glycosidic linkage. Stachyose This disaccharide is an entirely different compound than maltose or cellobiose, both of which involve two glucose molecules connected, respectively, via α (1 to 4) and β (1 to 4) glycosidic linkages. OLIGOSACCHARIDES 3 – 10 Monosaccharides combine together to form oligosaccharides (“Oligo” = few / small quantities) Joining of 3-10 monosaccharides by O-glycosidic bond: - Two naturally occurring oligosaccharides found in onions, cabbage, broccoli, brussel sprouts, whole wheat, and all types of beans Nystose 1. Raffinose = galactose + glucose + Represents a fructooligosaccharide with two fructose fructose molecules linked via beta(1----2) bonds to the fructosyl moiety of sucrose. This tetrasaccharide was subjected to 2. Stachyose = galactose + galactose + an array of in vitro tests designed for the assessment of glucose + fructose potential sugar substitutes before animal or human 3. Nystose = fructose + fructose + studies. fructose + galactose Humans lack the digestive enzymes necessary to metabolize either raffinose or stachyose. Hence these oligosaccharides, when ingested in food, pass undigested Raffinose Can be hydrolyzed to D-galactose and sucrose by the enzyme α-galactosidase (α-GAL), an enzyme synthesized by bacteria found in the large intestine It is non-digestible in humans and other monogastric who do not possess the αGAL enzyme to break down RFOs. These oligosaccharides pass undigested through the 11  ABO Blood Type & Oligosaccharides Human blood is classified into four types: A, B, AB, and O. The biochemical basis for the various types of blood involves oligosaccharide molecules that are attached to The absence or presence of a fifth monosaccharide the plasma membrane of red blood cells. (attached to the second galactose) determines the Four monosaccharides contribute to the make-up of the blood type. oligosaccharide “marking system. COMPLEX CARBOHYDRATES The arrangement of these monosaccharides in the In nutrition, monosaccharides and disaccharides are biochemical marker determines blood type. called simple carbohydrates, and polysaccharides are called complex carbohydrates. A polysaccharide is a polymer that contains many monosaccharide units bonded to each other by glycosidic linkages. Polysaccharides are often also called glycans. Homopolysaccharides: Branched (Storage Polysaccharides): - Glycogen and starch (α-glycosidic polymer) Unbranched (Structural Polysaccharides): - Cellulose (β-glycosidic polymer), chitin Homopolysaccharides: E.g., GAGs, Hyaluronic Acid, Heparin PARAMETERS TO DISTINGUISH GLYCANS FROM ONE TO ANOTHER 1. The identity of the monosaccharide repeating unit(s) in the polymer chain. A homopolysaccharide is a polysaccharide in which only one type of monosaccharide monomer is present A heteropolysaccharide is a polysaccharide in which more than one (usually two) type of monosaccharide monomer is present 2. The length of the polymer chain 3. The type of glycosidic linkage between monomer units. 4. The degree of branching of the polymer chain. Unlike monosaccharides and most disaccharides, polysaccharides are not sweet and do not test positive in Tollens and Benedict’s solutions. They have limited water solubility because of their size. However, the -OH groups present can individually become hydrated by water Note that all three of the oligosaccharide markers molecules. The result is usually a thick colloidal have a common four monosaccharide sequence in suspension of the polysaccharide in water. their structure: Polysaccharides, such as flour and cornstarch, are often used as thickening agents in sauces, desserts, and gravy. 12  4. Glycogen is about three times more highly branched than amylopectin, and it is much larger, with up to 1,000,000 glucose units present. POLYSACCHARIDES Cellulose – unbranched glucose polymer; structural component of plant cell walls, is the most abundant naturally occurring polysaccharide 1. The “woody” portions of plants 2. Glucose residues present in cellulose have a beta-configuration 3. Cellulose molecules tend to have linear structures 4. contain about 5000 glucose units POLYSACCHARIDES 5. Humans lack the enzymes (cellulase) capable of catalyzing the Starch hydrolysis of b(1 : 4) linkages in cellulose. – long chains of glucose found in plants; energy storage of plants – second most abundant naturally occurring polysaccharide; When the cell cannot get enough glucose from outside the cell, it 1. to give rigidity to the exoskeletons of crabs, lobsters, shrimp, hydrolyzes starch to release glucose. insects, and other arthropods 1. Cereal grains 2. cell walls of fungi (wheat, rice, corn, etc.), legumes (beans & peas), and root 3. identical to cellulose, except the monosaccharide present is the vegetables (potatoes, yams). glucose derivative N-acetyl-D-glucosamine (NAG) rather than 2. Amylose D-glucose itself. a straight-chain glucose polymer usually accounts for 15%–20% of 4. Chitin polymers contain both glycosidic linkages and amine the starch; amylopectin, a branched glucose polymer, accounts for bonds, both of which can be broken via hydrolysis. the remaining 80%–85% of the starch. 3. Iodine is often used to test for the presence of starch in solution; Starch containing solutions turn a dark blue-black when iodine is added Amylopectin, the other polysaccharide in starch, has a high degree of branching in its polyglucose structure. A branch occurs about once every 25 - 30 glucose units. The branch points involve a(1 →6) linkages & a(1→4) linkages; Up to 100,000 glucose units present. POLYSACCHARIDES Glycogen – long chains of glucose found in animals and humans – Also known as “animal starch” 1. Stored in liver & muscles 2. Helps maintain blood glucose and important source of “quick energy”, esp. during exercise (lasts only about 12 hrs) 3. Glycogen has a structure similar to that of amylopectin; all glycosidic linkages are of the a type, and both (1 → 4) and (1 → 6) ACIDIC POLYSACCHARIDES linkages are present. 13  is a polysaccharide with a disaccharide repeating unit in glucose, thus pushing blood glucose levels back up to normal. which one of the disaccharide components is an amino sugar and one or both disaccharide components has a THE GLUCOSE JOURNEY negative charge due to a sulfate group or a carboxyl - from food to fuel via the bloodstream group. Glucose starts its journey as a carbohydrate food. acidic polysaccharides are heteropolysaccharides; two When the food is eaten, It passes through the mouth, different monosaccharides are present in an alternating stomach and small intestine. pattern. All of these areas help to digest (break down) the food to Acidic polysaccharides are involved in a variety of cellular glucose. functions and tissues Glucose starts its journey as a carbohydrate food. Two of the most well-known acidic polysaccharides are When the food is eaten, it passes through the mouth, hyaluronic acid and heparin, both of which have stomach and small intestine. unbranched-chain structures. All of these areas help to digest (break down) the food to HYALURONIC ACID HEPARIN glucose. The glucose is absorbed from the small intestine into the The structure of hyaluronic It consists of repeating unit are blood stream. acid contains alternating a sulfate derivative of The blood stream carries the glucose to its next stop, all residues of N-acetyl-b-D D-glucuronate the body's cells, particularly muscles, the brain and the glucosamine (NAG) and (Dglucuronate-2-sulfate) and a liver. D-Glucuronate. doubly sulfated derivative of The glucose can only enter the cells with the help of D-glucosamine Alternating pattern of (N-sulfo-D-glucosamine-6-sulf insulin, a hormone which is made in the pancreas. glycosidic bond types, ate) As the blood glucose level rises after eating, the pancreas b(1 :→3) and b(1 → 4) releases insulin into the blood stream. Insulin travels to the cells, where it works to allow glucose to enter the cells. BLOOD SUGAR Glucose is also directed to the liver to be stored for later Blood sugar or blood glucose refers to sugar that is transported use. through the bloodstream to supply energy to all the cells in our Between meals and overnight our body can draw on the bodies. The sugar is made from the food we eat. The human body stored glucose for energy. regulates blood glucose levels so that they are neither too high nor Digestion too loW. Mouth Or –Salivary amylase (carbohydrates), Lingual lipase (lipids) Sugar is a simple, crystalline, edible carbohydrate and comes in a Stomach variety of forms, all of them sweet. Our body digests carbohydrates –Fibers and satiety, Pepsin (Proteins) into glucose, a simple sugar that can easily convert to energy. The Small Intestine chemical formula for glucose is C6H1206 -Maltase, sucrase, lactase The human digestive system breaks down the Pancreas carbohydrates from food into various sugar molecules - –Pancreatic amylase (CHO), Trypsinogen (Proteins), Pancreatic one of them is glucose, the body's principal source of Lipase (Lipids), Nucleases (Nucleic Acids) energy. The glucose goes straight from the digestive Large Intestine system into the bloodstream after we have consumed and -Fermentation of viscous fibers → Water, gas, short-chain fatty digested food. Glucose can only enter cells if there is acid production. insulin in the bloodstream too. Without any insulin the cells would starve. After we eat, blood sugar concentrations rise, the pancreas releases insulin automatically so that the glucose enters cells, as more and more cells receive glucose, blood sugar levels come down to normal again. Excess glucose is stored as glycogen (stored glucose in the liver and muscles. After a meal blood glucose levels rise, insulin is released from the pancreas into the bloodstream, blood sugar levels fallback. If you have not eaten for a while and blood glucose concentrations keep dropping, the pancreas releases another hormone called glucagon. Glucagon triggers the breakdown of glycogen into 14  METABOLISM - Glucose in the Body Used for energy – fuels most of the body’s cells Stored as glycogen – 1/3 in the liver and 2/3 in muscles Made from protein – gluconeogenesis Converted to fat – when in excess of body’s needs Constancy of Blood Glucose Regulating hormones – maintain glucose homeostasis 1. Insulin – moves glucose from the blood into cells. 2. Glucagon – signals the liver to release glucose into the blood. 3. Epinephrine – released when emergency fuel needed. Regulation of Carbohydrate Metabolism INSULIN is the primary hormone responsible for the entry of Regulation of Carbohydrate Metabolism glucose into the cell. Two hormones produced by the adrenal gland affect carbohydrate It is synthesized by the ß-cells of the islets of Langerhans metabolism: Epinephrine & Glucocorticoids in the pancreas. 1. Epinephrine (adrenal medulla) When these cells detect an increase in body glucose, they increases plasma glucose by inhibiting insulin secretion, release insulin. increasing glycogenolysis, and promoting lipolysis. The release of insulin causes an increased movement of is released during times of stress. glucose into the cells and increase glucose metabolism. is normally released when glucose levels are high and 2. Glucocorticoids (cortisol) is not released when glucose levels are decreased. are released from the adrenal cortex on stimulation by It decreases plasma glucose levels by increasing the adrenocorticotropic hormone (ACTH). transport entry of glucose in muscle and adipose tissue by Cortisol increases plasma glucose by decreasing intestinal way of nonspecific receptors. entry into the cell and increasing gluconeogenesis, liver It also regulates glucose by increasing glycogenesis, glycogen, and lipolysis. lipogenesis and glycolysis and inhibiting glycogenolysis. Regulation of Carbohydrate Metabolism Insulin is the only hormone that decreases glucose levels Two anterior pituitary hormones, growth hormone and ACTH, and can be referred to as hypoglycemic agent. promote increased plasma glucose. GLUCAGON 1. Growth hormone is the primary hormone responsible for increasing increases plasma glucose by decreasing the entry of glucose levels. glucose into the cells and increasing glycolysis. It is synthesized by the α-cells of islets of Langerhans in Its release from the pituitary is stimulated by decreased the pancreas and released during stress and fasting glucose levels and inhibited by increased glucose. states. Decreased levels of cortisol stimulate the anterior pituitary When these cells detect a decrease in body glucose, to release ACTH. they release glucagon. 2. ACTH Glucagon acts by increasing plasma glucose levels by in turn, stimulates the adrenal cortex to release cortisol glycogenolysis in the liver and an increase in and increases plasma glucose levels by converting liver gluconeogenesis. glycogen to glucose and promoting gluconeogenesis. It can be referred to as hypoglycemic agent. Regulation of Carbohydrate Metabolism 15 Two other hormones affect glucose levels: thyroxine and Type 2 diabetes – Gestational diabetes mellitus somatostatin. 1. Type 1 diabetes 1. Thyroid gland is characterized by inappropriate hyperglycemia primarily a result of is stimulated by the production of thyroid-stimulating hormone to pancreatic islet ßcell destruction and a tendency to ketoacids. release thyroxine that increases plasma glucose by increasing 2. Type 2 diabetes glycogenolysis, gluconeogenesis and intestinal absorption of In contrast, includes hyperglycemia cases that result from insulin glucose. resistance with an insulin secretory defect. 2. Somatostatin Diabetes Mellitus produced by the δ-cells of the islets of Langerhans of the pancreas, An intermediate stage, in which the fasting glucose is increases plasma glucose levels by the inhibition of insulin, increased above-normal limits but not to the level of glucagon, growth hormone and other endocrine hormones. diabetes, has been named impaired fasting glucose. Use of the term impaired glucose tolerance to indicate HYPOGLYCEMIA glucose tolerance values above normal but below diabetes The warning signs and symptoms of hypoglycemia are all levels was retained. related to the central nervous system. Also, the term GDM was retained for women who develop The release of epinephrine into the systemic circulation glucose intolerance during pregnancy and of norepinephrine at nerve endings of specific Type 1 diabetes mellitus neurons acts in unison with glucagon to increase plasma is a result of cellular-mediated autoimmune destruction of glucose. the ß-cells of the pancreas, causing an absolute deficiency Glucagon is released from the islet cells of the pancreas of insulin secretion. and inhibits insulin. Upper limit of 110 mg/dL on the fasting plasma glucose is Hypoglycemia involves decreased plasma glucose designated as the upper limit of normal blood glucose. levels and can have many causes – some are transient Type 1 constitutes only 10% to 20% of all cases of and relatively significant, but others can be life diabetes and commonly occurs in childhood and threatening. adolescence. The plasma glucose concentration at which glucagon and Initiated by an environmental factor or infection (usually a other glycemic factors are released is between 65 and 70 virus) in individuals with a genetic predisposition and mg/dL (3.6 to 3.9 mmol/L); at about 50 to 55 mg/dL (2.8 causes the immune destruction of the ß-cells of the to 3.1 mmol/L), observable symptoms of hypoglycemia pancreas and, a decreased production of insulin. appear. Characteristics of type 1 diabetes include abrupt onset, HYPERGLYCEMIA insulin dependence, and ketosis tendency. is an increase in plasma glucose levels. This diabetic type is genetically related. In healthy patients, during a hyperglycemia state, insulin is One or more of the following markers are found in 85% to secreted by the ß-cells of the pancreatic islets of 90% of individuals with fasting hyperglycemia: islet cell Langerhans. autoantibodies, insulin autoantibodies, glutamic acid Insulin enhances membrane permeability to cells in the decarboxylase autoantibodies and tyrosine phosphatase liver, muscle and adipose tissue. autoantibodies. It also alters the glucose metabolic pathways. Signs and symptoms include: Hyperglycemia, or increased plasma glucose levels, is polydipsia (excessive thirst) caused by an imbalance of hormones. polyphagia (increased food intake) Constancy of Blood Glucose polyuria (excessive urine production) rapid weight loss Diabetes hyperventilation –Type 1 diabetes / Juvenile Failure of insulin production mental confusion possible loss of consciousness (due to increased Obesity glucose to brain). –Type 2 diabetes / Adult Complications include: Onset microvascular problems such as nephropathy, neuropathy, and ret Autoimmune Increased heart disease is also found in patients with diabetes. –Type 3C diabetes Idiopathic type 1 diabetes Hypoglycemia Rare in healthy people is a form of type 1 diabetes that has no known etiology, is strongly inherited, and does not have ß-cell autoimmunity. Glycemic response Glycemic index Individuals with this form of diabetes have episodic requirements for insulin replacement. Laboratory Findings in Hyperglycemia: Diabetes Mellitus Increased glucose in plasma and urine is actually a group of metabolic diseases characterized by Increased urine specific gravity hyperglycemia resulting from defects in insulin secretion, insulin Increased serum and urine osmolality action, or both. Ketones in serum and urine (ketonemia and ADA/WHO guidelines recommend the following categories: ketonuria) Type 1 diabetes – Other specific types of diabetes Decreased blood and urine pH (acidosis) 16  Electrolyte imbalance 4. Formation of (Hb A1c) is nonenzymatic and occurs over the life Type 2 diabetes mellitus span (average 120 days) of the red blood cell. is characterized by hyperglycemia as a result of an 5. Because RBC is freely permeable to blood glucose, the amount individual’s resistance to insulin with an insulin secretory of total Hb A1c is related to the time averaged glucose defect. concentration over the 4 to 6 weeks before the measurement. This resistance results in a relative, not an absolute, 6. A level of 8% or less is considered “good” glycemic control. insulin deficiency. 7. The test is not used to diagnose diabetes. Type 2 constitutes the majority of the diabetes cases. 8. Common analyzers can use an enzymatic assay: diazyme A1c. Most patients in this type are obese or have an increased 9. Other methods: electrophoresis, ion-exchange chromatography, percentage of body fat distribution in the abdominal and high-performance liquid chromatography. region. Diabetes Mellitus This type of diabetes often goes undiagnosed for many Women identified through the oral glucose tolerance should years and is associated with a strong genetic receive a diagnosis of GDM. predisposition, with patients at increased risk with an Diagnostic Criteria for GDM: increase in age, obesity and lack of physical exercise. 1. FPG ≥ 92 mg/dL (5.1 mmol/L) Characteristics usually include adult onset of the disease 2. One-hour plasma glucose ≥ 180 mg/dL (10 mmol/L) and milder symptoms than in type 1, with ketoacidosis 3. Two-hour plasma glucose ≥ 153 mg/dL (8.5 mmol/L) seldom occurring. Causes of GDM include metabolic and hormonal changes. However, these patients are more likely to go into a Patients with GDM frequently return to normal postpartum. hyperosmolar coma and are at an increased risk of However, this disease is associated with increased developing macrovascular and microvascular perinatal complications and an increased risk for the complications. development of diabetes in later years. Other specific types of diabetes are associated with Infants born to mothers with diabetes are at increased risk certain conditions (secondary), including genetic defects of for respiratory distress syndrome, hypocalcemia, and ß-cell function or insulin action, pancreatic disease, hyperbilirubinemia. diseases of endocrine origin, drug- or chemical-induced Fetal insulin secretion is stimulated in the neonate of a insulin receptor abnormalities, and certain genetic mother with diabetes. syndromes. However, when the infant is born and the umbilical cord is The characteristics and prognosis of this form of diabetes severed, the infant’s oversupply of glucose is abruptly depend on the primary disorder. terminated, causing severe hypoglycemia. Maturity-onset diabetes of youth is a rare form of diabetes that is inherited in an autosomal dominant fashion. GDM has been defined as any degree of glucose intolerance with onset or first recognition during pregnancy. However, the latest recommendations suggest that “high risk” women found to have diabetes at their initial prenatal visit, using standard criteria receive a diagnosis of overt, not gestational diabetes Diagnostic Criteria for Diabetes Mellitus 1. HbA1c ≥ 6.5% using a method that is NGSP certified and standardized to the DCCT assay. 2. Fasting plasma glucose ≥ 126 mg/ dL (≥ 7.0 mmol/L) 3. Two hour plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L during OGTT. 4. Random plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L plus symptoms of diabetes. Microalbuminuria NGSP (National Glycohemoglobin Standardization Program) DM causes progressive changes to the kidneys and OGTT (Oral Glucose Tolerance Test) ultimately results in diabetic renal nephropathy. This complication progresses over years and may be NOTE: In the absence of unequivocal hyperglycemia, these criteria delayed by aggressive glycemic control. should be confirmed by repeat testing on a different day. The fourth An early sign that nephropathy is occurring is an increase measure (OGTT) is not recommended for routine clinical use in urinary albumin. Glycosylated Hemoglobin is defined as persistent albuminuria 1. Long term estimation of glucose concentration - Measurement of in two out of three urine collections of 30 to 300 mg/24 h, glycosylated hemoglobin(Hb A1c). 20 to 200 µg/min, or an albumin-creatinine ratio ≥ 300 2. Hemoglobin A (Hb A) is formed when glucose binds to amino mg/24 h, >200 µg/min, or ≥ 300 µg/mg. group that is part of the Hb A protein. Although three methods for microalbuminuria screening 3. The reaction occurs at the N-terminal valine of the hemoglobin are available, the use of random spot collection for the beta chains. measurement of the albumin creatinine ratio is the preferred method. 17  NATURAL SUGAR intake with emphasis on complex is a sugar naturally present in whole foods. -Daily Value: 300 g/day Milk and fresh fruit are two important sources of natural Fiber sugars. –Daily Value: 25 g/day REFINED SUGAR –AI: 14 g/1000 kcal/day is a sugar that has been separated from its plant source. Alternative Sweeteners Sugar beets and sugar cane are major sources of refined Two Categories sugars 1. Sugar Alcohols – mannitol, sorbitol, xylitol 2. Artificial sweeteners – sugar substitutes (calorie-free); in Health Effects of Sugar moderation, useful for blood sugar & weight control Sugar in excess 1. Sugar Alcohols 1. Contains no nutrients and may contribute to malnutrition 1. CHOs that provide less energy than sucrose (2-3 kcals/gm) 2. Causes dental caries (tooth decay) because not completely absorbed 3. Does not cause, but can contribute to: obesity, diabetes, heart 2. May cause gas, abdominal discomfort, diarrhea disease, & behavorial problems 3. Less cariogenic than sugar 2. Artificial Sweeteners Recommended Intakes of Sugars 1. Saccharin = “Sweet ‘N Low” or “Sugar Twin” DRI 2. Aspartame = “Equal” or “Nutrasweet” must avoid if have – No more than 25% of total daily energy intake phenylketonuria – Limit added sugars to