BIOCHEM_LC5_INTRODUCTION TO CARBOHYDRATES AND GLYCOLYSIS.pdf

C6H12O6 COURSE OUTLINE I. CARBOHYDRATES II. TYPES OF CARBOHYDRATES A. Simple Carbohydrates a. Monosaccharides b. Disaccharides B....

C6H12O6 COURSE OUTLINE I. CARBOHYDRATES II. TYPES OF CARBOHYDRATES A. Simple Carbohydrates a. Monosaccharides b. Disaccharides B. Complex Carbohydrates a. Oligosaccharides b. Polysaccharides III. CARBOHYDRATE-NON CARBOHYDRATE LINKAGES IV. ISOMERS V. EPIMERS VI. ENANTIOMERS VII. DETECTION OF CARBOHYDRATES A. Molisch’s Test B. Benedict’s Test C. Barfoed’s Test Figure 1. Zephyr, NIKI, 2018 D. Seliwanoff’s Test II. TYPES OF CARBOHYDRATES E. Hydrolysis Test for Sucrose F. Phloroglucinol Test G. Osazone’s Test Simple Carbohydrates H. Bial’s Test ○ Monosaccharides I. Iodine Reaction ○ Disaccharides VIII. Digestion of Carbohydrates Complex Carbohydrates A. Salivary and Pancreatic Alpha ○ Oligosaccharides Amylase B. Intestinal Disaccharides ○ Polysaccharides C. Intestinal Absorption of Monosaccharides Simple Carbohydrates: IX. Glycolysis a. MONOSACCHARIDES A. Steps in Glycolysis B. Hexokinase vs. Glucokinase Simple sugars X. Malfunctions of Glycolysis Carbohydrate that contains an aldehyde A. Hexokinase Deficiency group (aldoses) or ketone group (ketoses) B. Other Malfunctions Cannot be broken down into simpler units XI. REFERENCES by hydrolysis reactions INTRODUCTION TO CARBOHYDRATES I. CARBOHYDRATES Carbohydrates/Saccharides Most abundant organic molecules in nature Functions ○ Dietary calories for most organisms; ○ Storage form of energy; Figure 2. Monosaccharides found in humans, classified based on number of carbons they contain ○ Cell membrane components; ○ Structural component of cell walls of bacteria, the exoskeleton of Types of carbonyl group they insects, and fibrous cellulose of contain: plants. ○ Aldoses ○ Ketoses - additional “ul” The Empirical Formula: (CH2O)n e.g. Xylulose Structure of Carbohydrates All carbohydrates contain carbon, hydrogen, and oxygen in 1:2:1 ratio BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 Glycosidic bonds between sugars are named according to: ○ Numbers of the connected carbons ○ Position of the anomeric hydroxyl group of the sugar involved α bond: anomeric hydroxyl group is in α configuration (same side) β bond: anomeric hydroxyl group is in β configuration (opposite side) Figure 3. Examples of an aldose (A) and a ketose (B) sugar Carbohydrates that have a free carbonyl group have the suffix -ose ○ e.g. Pentose, Hexose Examples of Monosaccharides: 1. Glucose 2. Fructose - fruits, honey, and vegetables 3. Galactose - milk Figure 6. Examples of Disaccharides Complex Carbohydrates Figure 4. Comparison of Glucose, Fructose, and Galactose structures a. OLIGOSACCHARIDES Contain 3 -10 monosaccharide units linked b. DISACCHARIDES by glycosidic bonds Contain two monosaccharide units Figure 7. Raffinose structure Figure 5. A glycosidic bond between two hexoses producing a disaccharide. PREPARED BY: BATCH 2028 1D 2 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 b. POLYSACCHARIDES O-glycosidic link Long chain polymers of monosaccharides ○ Sugar is attached to -OH group (>10) connected by glycosidic bonds ○ Linkage of all sugar-sugar Polysaccharide made up of a glucose glycosidic bonds units: Starch, Glycogen, and Cellulose Figure 10. Glycosides: examples of N- and O-glycosidic Figure 8. Polysaccharide consists of glucose molecules. Figure 9. Comparison of starch, glycogen, and cellulose structure Starch is used for energy storage in plants. ○ Amylose: continuous unbranched chains of glucose units ○ Amylopectin: continuous branched chains of glucose units Glycogen acts as an energy-reserved carbohydrate for animals. ○ Branched polysaccharide Figure 11. Carbohydrate classification and Nomenclature ○ Liver and muscle Cellulose is the most widely distributed polysaccharide in plant cell wall. IV. ISOMERS ○ Linear, well-organized ○ Parallel chains in bundles Same chemical formula but have different ○ Cannot be digested by humans structures and other animals C6H12O III. CARBOHYDRATE-NON-CARBOHYDRATE LINKAGES Purine Aromatic rings Proteins Figure 12. Shows Glucose and Fructose as isomers Lipids and Glucose and Galactose as epimers. N-glycosidic link ○ Non-carbohydrate molecule to which the sugar is attached is an -NH2 group PREPARED BY: BATCH 2028 1D 3 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 V. EPIMERS A. MOLISCH’S TEST Confirm presence of carbohydrate in a Carbohydrates isomers that differ in given solution configuration around only one specific REAGENTS carbon atom ○ 5% alpha-naphthol solution in ethyl alcohol APPARATUS ○ Test tube ○ Dropper or pipette ○ Solution to be tested PROCEDURE 1. Take 2mL of CHO solution in a clean Figure 13. Glucose, Galactose, and Mannose and dry test tube. 2. Add 2gtts of ethanolic alpha naphthol VI. ENANTIOMERS (Molisch reagent) and mix. 3. Incline the test tube and carefully add Mirror images 2mL of concentrated sulphuric acid along D- and L- sugars the side of the test tube to form 2 layers. RESULT: ○ (+) PURPLE RING Figure 14. L-Glucose and D-Glucose B. BENEDICT’S TEST VII. DETECTION OF CARBOHYDRATES Test for reducing sugars Negative for polysaccharides Benedict’s qualitative reagent ○ Copper sulfate ○ Sodium Carbonate ○ Sodium Citrate Apparatus ○ Test tube/holder ○ Dropper/pipette ○ Gas lamp ○ Solution to be tested PROCEDURE 1. Take 5mL of Benedict’s Qualitative reagent in the test tube. 2. Add 8 drops of the given solution above the test tube. Figure 15. Steps for detection of carbohydrates from unknown 3. Mix the solutions. samples 4. Hold the test tube on flame and boil for 2 minutes. 5. Allow the solution to cool. 6. Look for the precipitates. PREPARED BY: BATCH 2028 1D 4 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 RESULT ○ (+) Brick-red precipitate D. SELIWANOFF’S TEST Differentiates fructose from glucose and galactose. REAGENTS ○ 50mg Resorcinol C. BARFOED’S TEST ○ 33mL of concentrated HCl Monosaccharides vs Disaccharides Apparatus REAGENT ○ Test tube/holder ○ Copper acetate in glacial acetic ○ Dropper/pipette acid ○ Gas lamp APPARATUS ○ Solution to be tested ○ Test tube/holder PROCEDURE ○ Dropper/pipette 1. Take 3mL of Seliwanoff’s reagent in the ○ Gas lamp test tube. ○ Solution to be tested 2. Add 1mL of test solution in the above PROCEDURE test tube. 1. Take 2mL of Barfoed’s reagent in the 3. Hold the test tube on flame and allow it test tube. to boil for 30 seconds. 2. Add 2mL of the test solution to the 4. Allow to cool at room temperature. above test tube. RESULTS 3. Mix the solutions. ○ (+) Deep cherry red: fructose 4. Hold the test tube on flame and boil for ○ (+) Cherry-red: sucrose minutes. 5. Allow to cool at room temperature. 6. Look for precipitates. 7. If no precipitates are formed, boil for an additional 10 minutes. 8. Allow to cool and look for the precipitates. RESULT ○ (+) Scanty brick-red precipitates PREPARED BY: BATCH 2028 1D 5 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 E. HYDROLYSIS TEST FOR PROCEDURE SUCROSE 1. Take 2mL of test solution in a test tube. 2. Add 2mL of Tollen’s reagent to the PRINCIPLE: above test tube. ○ Sucrose on hydrolysis with HCl is 3. Mix the 2 solutions thoroughly. converted to glucose and 4. Hold the test tube on flame and boil for fructose. some time. ○ The presence of these two 5. Allow to cool at room temperature. monosaccharides can be RESULT confirmed with Benedict’s and ○ (+) Red color Seliwanoff’s test. PROCEDURE: 1. Add 2 drops of HCl and one drop of thymol blue to 5mL of sucrose solution. 2. The development of pink color indicates that the solution is acidic. Divide it into 2 equal parts. 3. Boil one portion for about 1 minute and then cool it under tap water. G. OSAZONE’S TEST 4. Neutralize both portions by adding 2% sodium carbonate drop by drop. Formation Confirm presence of carbohydrates of blue color indicates neutralization. REAGENT: Osazone mixture 5. Perform Benedict’s and Seliwanoff’s ○ 1 part Phenyl Hydrazine with a boiled portion. Boiled portion gives a ○ 2 parts Sodium Acetate positive test with Benedict’s, but the ○ Few drops of glacial acetic acid unboiled portion does not reduce Apparatus Benedict’s solution. ○ Test tube/holder RESULTS ○ Dropper/pipette ○ (+) Orange color ○ Gas lamp ○ Solution to be tested PROCEDURE 1. Take 5mL of the given solution in a test tube. 2. Add 3 pinches of Osazone mixture to the above test tube. 3. Mix thoroughly. 4. Hold the test tube on flame and boil for 5 minutes. 5. Check for yellow crystals. If not formed, boil further. 6. Keep checking after every 5 minutes for yellow crystals. 7. Once the crystals are formed, allow the solution to cool at room temperature. 8. Take the crystals out and prepare a F. PHLOROGLUCINOL TEST slide. 9. Observe the slide under the microscope. Test for galactose and lactose. RESULT: Formation of crystals under the REAGENT: Tollen's reagent microscope (Phloroglucinol) 1. Needle shaped in 5 mins: GLUCOSE ○ 10mL concentrated HCl mixed 2. Needle shaped in 2 mins: FRUCTOSE with 8mL of 0.5% phloroglucinol 3. Needle shaped in 30 mins: MANNOSE Apparatus 4. Sunflower shaped: MALTOSE ○ Test tube/holder 5. Balls with thorny edge: GALACTOSE ○ Dropper/pipette 6. Fine-long needle: XYLOSE ○ Gas lamp 7. Powder puff/hedge hog: LACTOSE ○ Solution to be tested PREPARED BY: BATCH 2028 1D 6 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 I. IODINE REACTION Test specific for polysaccharides REAGENT: Iodine reagent ○ 0.5mL iodine diluted in 5mL distilled water APPARATUS ○ Test tube ○ Dropper/pipette ○ Solutions to be tested PROCEDURE 1. Take 2mL of the given solution in the test tube. 2. Add 2-3 drops of iodine reagent in the above test tube. 3. Wait for some time. INTERPRETATION ○ Amylose - a linear chain H. BIAL’S TEST component of starch gives deep PRINCIPLE blue color. ○ The test reagent dehydrates ○ Amylopectin - a branched chain pentoses to form furfural. component of starch gives purple ○ Furfural further reacts with color. original orcinol and the iron ion ○ Glycogen - gives reddish brown present in the test reagent to color. produce a bluish product useful in ○ Dextrins - amylo, erythron and distinguishing pentoses sugar achdectrins formed as from hexoses sugars. intermediates during hydrolysis of ○ Pentoses (sucrose as ribose starch give violet, red and no sugar) from furfural in acidic color with iodine respectively. medium which condense with orcinol in presence of ferric ion to give blue green colored complex which is soluble in butyl alcohol. PROCEDURE 1. Add 3mL of Bial’s reagent in an empty test tube. 2. Add 3mL of test solution to the above test tube. 3. Heat the test tube in boiling water bath. 4. Allow the solution to cool at room temperature. RESULT ○ (+) Blue-green color PREPARED BY: BATCH 2028 1D 7 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 SUMMARY OF TESTS The salivary and pancreatic alpha amylase take part in breaking down the polysaccharides starting from the mouth. Salivary alpha amylase is the first to react to the food that you ingest. Our digestive system utilizes proteases to break them down into smaller components. The major dietary polysaccharides are of plant (starch, composed of amylose and amylopectin) and animal (glycogen) origin. Salivary alpha amylase is found in the mouth, where the digestion of starches and glycogen is initiated by hydrolyzing alpha-1,4 bonds. VIII. DIGESTION OF CARBOHYDRATES Humans cannot digest cellulose because salivary alpha amylase can only break The principal sites of dietary carbohydrate down alpha bonds. Celluloses have beta digestions are the mouth and the bonds. Therefore, we are unable to digest intestinal lumen. cellulose—a carbohydrate of plant origin This process is rapid and catalyzed by the containing β(1→4) glycosidic bonds enzymes known as glycoside between glucose residues. hydrolases, or glycosidases, that Because branched amylopectin and hydrolyze glycosidic bonds. glycogen also contain α(1→6) bonds, Glycosidic bonds found in disaccharides which α-amylase cannot hydrolyze, the and complex sugars like polysaccharides, digest resulting from its action contains a are the first to be broken down by mixture of short, branched and glycoside hydrolases. Little unbranched oligosaccharides known as monosaccharides are present in diets of dextrins. mixed animal and plant origin. The enzymes are primarily endoglycosidases that hydrolyze polysaccharides and oligosaccharides. Disaccharides are broken down by disaccharidases. These hydrolyze disaccharides into their reducing sugars. Figure 17. Degradation of dietary glycogen by salivary or pancreatic alpha amylase. Figure 16. Hydrolysis of a glycosidic bond. After mastication in the mouth, the food passes through the esophagus and then finally, the stomach. The hydrochloric acid in the stomach contributes to its acidic A. SALIVARY AND PANCREATIC environment which neutralizes or ALPHA AMYLASE inactivates the amylase, temporarily stopping digestion in the stomach. When Polysaccharides are inherently too large the acidic stomach contents reach the (e.g. glycogen in meat) to be transported in small intestine, they are neutralized by the intestine. Thus, the polysaccharides bicarbonate secreted by the pancreas, and should be broken down into smaller units. pancreatic α-amylase continues the PREPARED BY: BATCH 2028 1D 8 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 process of starch digestion. Bicarbonate and pancreatic alpha amylase are secreted by the pancreas and further digest the dextrins into maltose, maltotriose, and isomaltose. In the intestine, absorption occurs. B. INTESTINAL DISACCHARIDES The final digestive processes occur primarily at the mucosal lining of the upper jejunum, and include the action of several disaccharidases. For example, isomaltase cleaves the α(1→6) bond in isomaltose and maltase cleaves maltose and maltotriose, each producing glucose, sucrase cleaves sucrose producing glucose and fructose, and lactase (β-galactosidase) cleaves lactose producing galactose and glucose. Figure 18. Digestion of carbohydrates (Note: indigestible cellulose enters the colon and is excreted.) C. INTESTINAL ABSORPTION OF MONOSACCHARIDES Absorption starts in the duodenum and most of the monosaccharide products are absorbed in the upper jejunum. Our intestine breaks down our polysaccharides into simple sugars first such as glucose, fructose, and galactose. Once they become simple sugars, they are absorbed by enterocytes. Most of the monosaccharides are absorbed by the upper jejunum, though absorption has begun in the duodenum. Figure 19. Absorption by enterocytes of the monosaccharide products of carbohydrate digestion. GLUT = glucose transporter; SGLT-1 = sodium (Na+)- dependent glucose cotransporter. K+ = potassium PREPARED BY: BATCH 2028 1D 9 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 Monosaccharides differ in the transporters of absorption: Fructose attaches to GLUT-5 in order to enter the intestine. Galactose and Glucose need the Sodium (Na+)-glucose linked transporter (SGLT1) transporter in order to be absorbed by the intestine, going into the portal circulation. GLUT-2 facilitates the absorption from the enterocyte into the portal system. Any genetic derangement in the coding of these transporters will lead to MALABSORPTION. SUCRASE-ISOMALTASE TREHALASE Sucrase and isomaltase are enzymic One catalytic site hydrolyzes α-1,1 activities of a single protein which is glycosidic bonds in trehalose cleaved into two functional subunits that Consumption of trehalose causes remain associated in the cell membrane, discomfort in enzyme deficient patients forming the sucrase-isomaltase complex. ○ Due to mushroom and insect Majority found in the jejunum, and has two consumption (2) catalytic sites: BETA-GLYCOSIDASE COMPLEX ○ Sucrase-maltase Has two (2) catalytic sites: ○ Isomaltase-maltase ○ Lactase - hydrolyzes β-bonds Catalyzes the hydrolysis of: connecting glucose and galactose ○ α-1,2 glycosidic bond of sucrose in lactose ○ α-1,4 glycosidic bond of maltose ○ Other site - hydrolyzes β-bonds ○ α-1,6 glycosidic bond of between galactose or glucose isomaltose and ceramide in glycolipids Lactose intolerance ○ Pain, nausea and flatulence after consumption of dairy products. Diminished lactase activity LACTASE DEFICIENCY LCT gene codes for LACTASE Leads to LACTOSE INTOLERANCE Lactose intolerance: deficiency in the enzyme lactase which is produced by the cell lining of the small intestine. If there will be no lactase, there will be no breakdown of lactose into glucose and galactose further leading to bacterial contamination. SUCRASE-ISOMALTASE DEFICIENCY The bacterial contamination leads to increased production of gas and acids in Autosomal-recessive disorder the large intestine leading to flatulence and 1:5,000 is affected by this deficiency abdominal pain. α-1,2 glycosidic bond linkage will not be Hydrogen breath test takes about 2-3 hydrolyze hours. The patient drinks a lactose-loaded Treatment: beverage. The bacterial fermentation of ○ Dietary restriction of sucrose malabsorbed sugar produces hydrogen. ○ Enzyme replacement therapy Gases are absorbed in the bloodstream and carried to the lungs. Normally, very low hydrogen is detected in the breath but undigested lactose products yield high levels of hydrogen. The breath is analyzed at regular intervals to measure the amount of hydrogen. PREPARED BY: BATCH 2028 1D 10 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 Stool acidity test is used for infants and X. GLYCOLYSIS children to measure the amount of acid in It is an aerobic process. the stool. Undigested lactose produces lactic acid and short chain fatty acids that can be detected in a stool sample. Figure 20. Abnormal lactose metabolism. Glycolysis has two (2) stages: The first five (5) steps of glycolysis is an energy-investment phase The remaining five (5) steps is an energy-generation phase. Figure 21. Urea breath test Glycolysis produces: 2 Pyruvate CLINICAL CASE: 2 ATP You are examining a patient complaining 2 NADH of cramping in the lower belly, bloating, gas, and A. STEPS IN GLYCOLYSIS diarrhea, flatulence, nausea. These symptoms Glucose cannot be absorbed directly by the cells appear within 30 mins to 2 hours after the ingestion 1. The first reaction in glycolysis involves the of dairy products. You advise your patient to avoid action of Hexokinase which catalyzes the foods that contain a particular sugar. What sugar phosphorylation of glucose into glucose should this patient avoid? 6-phosphate (G6P) 2. G6P is converted to fructose 6-phosphate ANSWER: Lactose (F6P) by phosphoglucose isomerase. Through rearrangement of the existing atoms without removal or addition of any of the atoms. 3. The phosphorylation of F6P is the rate-limiting and committed step of glycolysis. Phosphorylation of F6P is catalyzed by phosphofructokinase 1 (PFK1), leading to fructose 1,6-bisphosphate PREPARED BY: BATCH 2028 1D 11 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 4. Aldolase catalyzes the cleavage of B. GLUCOKINASE vs. HEXOKINASE Fructose 1,6-bisphosphate, leading to the production of Glyceraldehyde 3-phosphate (G3P) and Dihydroxyacetone phosphate (DHAP). 5. DHAP does not proceed to the next step of glycolysis. DHAP must always be isomerized or converted to G3P. 6. G3P Oxidation is the first redox reaction in glycolysis. 7. G3P is converted to 1,3-bisphosphoglycerate (1,3BPG) by the action of Glyceraldehyde 3-phosphate dehydrogenase (G3PDH) or Triose phosphate dehydrogenase. 8. Note that the 1,3 BPG will be converted to 3-phosphoglycerate (3PG) by phosphoglyceratekinase (PGK) in the glycolysis pathway. But in RBCs, 1,3 BPG will be converted first to 2,3 BPG and will be acted upon by the phosphatase to be converted into 3PG for the glycolysis to proceed. 9. In 3PG, the phosphate group is shifted or rearranged by phosphoglycerate mutase (PGM) which catalyzes the reversible conversion of 3PG to 2-phosphoglycerate (2PG). But for the glycolysis to proceed, it The hexokinase step of glycolysis is a rate should be 2PG. limiting step 10. The conversion of 2PG into Hexokinase transfer phosphate group from phosphoenolpyruvate (PEP) by enolase is ATP to glucose a dehydration reaction and leads to the Phosphorylated glucose is trapped within production of water. cell and allows for more glucose 11. PEP contains a high energy enol movement into the cell phosphate. In this phase, the conversion of Hexokinase is regulated by G6P and PEP to pyruvate by pyruvate kinase (PK) glucose availability is also irreversible. Hexokinase deficiency makes for less 12. PEP is catalyzed by PK to become glucose and slower glycolysis pyruvate. The phosphate from the PEP is Hexokinase has higher affinity to glucose added to the ADP to become ATP, hence than glucokinase. producing the pyruvate. 13. Pyruvate is the end product of glycolysis. The fates of pyruvate are: Can be converted to Lactate, which enters the Lactic acid cycle Can be converted to Acetyl-Coenzyme A (Acetyl-CoA) which is a precursor for the Tricarboxylic Acid Cycle (TCA), also known as Krebs cycle Can be converted to oxaloacetate (OAA), which is a part of Krebs cycle Can be converted to acetaldehyde by Hexokinase I,II,III are present in most tissues and pyruvate decarboxylase (PDC), and are inhibited by their product, G6P. acetaldehyde is subsequently converted to ethanol by alcohol dehydrogenase (ADH) Glucokinase is also known as Human ”Hexokinase IV” (HK4) and is specific for glucose. PREPARED BY: BATCH 2028 1D 12 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 XI. MALFUNCTIONS OF GLYCOLYSIS B. OTHER MALFUNCTIONS Mutations that occur and deter the chain of Muscle phosphofructokinase deficiency reaction Aldolase deficiency Any problem or any glitch in the genetic Enolase deficiency makeup of a person may distort the chain Pyruvate kinase deficiency - most common of reaction involved in the process of glycolysis Mostly autosomal recessive Due to defective enzymes (absent or deficient) A. HEXOKINASE DEFICIENCY DIAGNOSIS: Jaundice PBS Hgb and Hct Increased Reticulocyte count Increased Lactate Dehydrogenase (LDH) Hexokinase deficiency leads to hereditary and nonspherocytic hemolytic anemia, common in pediatric patients. Hexokinase deficiency in RBC results to: → reduced formation of 2,3 BPG → hemoglobin deliver less oxygen to tissue → leading to HEMOLYTIC ANEMIA Hexokinase or Glucokinase functions as a glucose sensor in blood glucose homeostasis. Inactivating mutations of glucokinase are the cause of a rare form of diabetes in young patients, which is type 1. Heterozygous mutation - (partial glucokinase deficiency) leads to maturity onset diabetes for the young (MODY) Homozygous mutation - (complete glucokinase deficiency) leads to permanent neonatal diabetes mellitus (PNDM) PREPARED BY: BATCH 2028 1D 13 BIOCHEMISTRY LC5a: INTRODUCTION TO CARBOHYDRATES DR. ABITONG-BOLISLIS DATE: 09/10/2024 LACTIC ACIDOSIS Lowered blood pH and bicarbonate levels due to elevated lactate in the blood. Causes: ○ Increased formation ○ Decreased utilization Reference(s): 1. Dr. Abitong-Bolislis (2024). Lecture and Powerpoint Presentation. PREPARED BY: BATCH 2028 1D 14