Carbohydrates Lecture I PDF

Carbohydrates Intended learning outcome At the end of the topic the student should be able to understand: 1. The metabolism of glucose in the body. 2. Various hormones that regulates its concentration in the blood 3. Different clinical condition relating abnormal blood glucose Outline 1....

Carbohydrates Intended learning outcome At the end of the topic the student should be able to understand: 1. The metabolism of glucose in the body. 2. Various hormones that regulates its concentration in the blood 3. Different clinical condition relating abnormal blood glucose Outline 1. Biochemistry of carbohydrates 2. Classification of carbohydrates 3. Metabolism of carbohydrates 4. Process of glucose metabolism 5. Hormonal regulation of glucose 6. Glycemic diseases Biochemistry of carbohydrate Biochemistry of carbohydrate Composed of C, H and O Carbon + water (hydrates of carbon). Contain C=O and –OH functional group General formula: C6(H12O)6 Water soluble, most are reducing sugar except sucrose. Stored in the body in the form of glycogen. Chemical structure of CHO Fisher projection Hayworth projection Open chain form Cyclic form Carbon are vertically connected by solid lines C-O and C-H horizontally connected. Classification of CHO Classification of CHO Based on the following 1. Number of carbon chain size 2. Number of sugar units 3. Difference in spatial arrangement (-OH position) Classification of CHO Based on carbon chain size 1. Trioses- 3 carbon 2. Tetroses- 4 carbon 3. Pentoses- 5 carbon 4. Hexoses- 6 carbon Glyceraldehyde- smallest carbon chain found in the body. Classification of CHO Based on number of sugar units 1. Monosaccharides 2. Disaccharides 3. Oligosaccharide 4. Polysaccharide Monosaccharide Also known as simple sugar. No further reduction in form. Hexoses (6 carbon atom) 1. Glucose 2. Fructose 3. Galactose Monosaccharide Pentoses (5 carbon atom) 1. Deoxyribose 2. Ribose Types of glucose in the body Based on the difference in spatial arrangement (position of hydroxyl group) but the same order of carbon and chemical bonds. 1. D-glucose- OH group on the right 2. L-glucose- OH group on the left D-glucose- most common sugar in the body. Fisher projection  Types of D-glucose They differ in the –H and – OH group direction in carbon atom 1 1. α- D-Glucose- predominant in starch 2. ß- D- Glucose – predominant in glycogen Hayworth projection and cellulose. Disaccharide Consist of 2 monosaccharides joined by glycosidic linkage. 1-4 glycosidic linkage ( 1st carbon atom of a monosaccharide is linked to 4th carbon of the other monosaccharide). glucose + glucose= maltose glucose + lactose= lactose sucrose- glucose + fructose= sucrose Disaccharides is hydrolyze by enzyme lactase present in the intestine. Oligosaccharides Composed of 3 to 10 monosaccharides some up to 20. In the body they are called glycans (glycoprotein and glycolipids) Glycosylation- process of binding oligosaccharide to proteins or lipids. Some participates in immune response 1. cell recognition- cell receptors 2. auto antigens (RBC antigen) Oligosaccharides- RBC antigen (ABO blood group) H-antigen- the building block or A and B antigen in RBC Polysaccharides Consist of many units of monosaccharides linked together by glycosidic bonds. Serves a storage of energy in human and plants. Integral part of the cell and tissue structure. Polysaccharides Exogenous 1. Starch- storage form in plants (amylopectin and amylose) 2. Cellulose- forms the cell wall of plants. Also known as dietary fiber. 3. Inulin- also known as fructans (dietary fibers) found in plants. Used for Glomerular filtration rate estimation. 4. Chitin- forms the cell wall of fungi and exoskeleton of arthropods Endogenous 5. Glycogen- storage form in human (liver) 6. Hyaluronic acid- lubricants of the joints 7. Heparin-natural anticoagulant in the blood Functions in the body 1. Major source of energy (glucose) in the body. 2. Found as part of the cell membrane of the cell, the glycoprotein and glycolipids. 3. Forms the building block (oligosaccharides) of ABO antigens in the surface of RBCs. 4. One of the major component of nucleotides (pentose) Carbohydrate metabolism Digestion in the GIT Starch and glycogen Starts from the mouth through action salivary amylase. (polysaccharides) In the small intestine hydrolysis occur by the action of pancreatic amylase, Limit dextrin and maltose maltase, sucrase and lactase to (Disaccharide) breakdown into monosaccharide From the duodenum Glucose, Galactose and and ileum Fructose monosaccharide is (Monosaccharide) absorbed into the blood circulation for further metabolism. Glucose metabolism in the blood Depending on the need of the body glucose can be; 1. Used as energy 2. Stored in the form of glycogen 3. Stored in the form of triglycerides 4. Converted in protein, amino acids and keto acids Used as energy Glucose is used for energy production through production of ATP, CO2 and H2O. Involve 3 process 1. Glycolysis 2. TCA cycle (Krebs cycle) 3. Electron transport chain Stored in the form of glycogen Stored in the form of glycogen in the liver and peripheral tissues like skeletal muscles through the process of glycogenesis. Stored as triglycerides (fats) Stored as triglycerides in adipose tissues through the process of lipogenesis. Converted into keto-acids, amino acids and protein. This occur in the skeletal muscle through the process of Cori cycle (glucose-alanine cycle). Process of glucose metabolism Process of glucose metabolism 1. Glycogenesis 2. Glycogenolysis 3. Gluconeogenesis 4. Glycolysis 5. Lipogenesis 6. Lipolysis Process of glucose metabolism Glycogenesis Conversion of excess glucose to glycogen to be stored in the liver and peripheral tissues. This process occur when cell already met the energy requirement, glucose is stored as glycogen. Reduces blood sugar level. Process of glucose metabolism Glycogenolysis Stored glycogen in the liver is broken down into glucose for energy production. This process occur during fasting state. Stimulated by glucagon and epinephrine. Inhibited by insulin. Increases blood sugar level. Process of glucose metabolism Gluconeogenesis Formation of Glucose-6- phosphate from non- carbohydrate source such lactate, amino acids (keto acids) and glycerol. Occurs in the liver, kidney, skeletal muscle, intestine, and brain. This process occur during prolong starvation. Increases the blood sugar level. Process of glucose metabolism Glycolysis – glucose is metabolized into pyruvate and lactate releasing energy (ATP). This process reduces blood sugar level. Process of glucose metabolism Lipogenesis Conversion of glucose into fatty acids for storage in adipose tissues. This occur when sufficient glycogen is already stored in the liver. Decrease blood sugar level. Process of glucose metabolism Lipolysis Fatty acids in adipose tissue is converted back to glucose to be used for energy production. Triglycerides is broken down to FA and oxidized (β- oxidation) into Acetyl CoA to be used to generate ATP. This process occur during prolong starvation. Increases blood sugar level. Process of blood sugar metabolism Increase blood sugar Decrease blood sugar 1. Glycogenolysis 1. Glycolysis 2. Gluconeogenesis 2. Glycogenesis 3. Lipolysis 3. Lipogenesis Hormonal regulation of blood glucose level Hormonal regulation of blood glucose level Insulin Glucagon Somatostatin (Hypoglycemic (Hyperglycemic (Regulator) agent) agent) Produced by pancreas the Produced by pancreas the Produced by pancreas beta islets of Langerhans. alpha islets of Langerhans delta islets of Langerhans. Release when plasma cells. glucose level increase Release when plasma Action thus lowering blood glucose decrease (stress Inhibits the release of glucose. and fasting state) insulin and glucagon. Actions include: therefore increasing blood Regulates the reciprocal a. Increase glycolysis, glucose. relationship of these glucogenesis and Actions include: hormones. lipogenesis a. Increases glycogenolysis, b. Decrease glycogenolysis gluconeogenesis and lipolysis. Hormonal regulation of blood glucose level Anterior pituitary Thyroid gland Adrenal gland gland Growth hormone (GH) Thyroxine (T4) Epinephrine (adrenal Increases blood glucose Increase blood glucose medulla) level thru glycogenolysis, Increases blood glucose Regulated by gluconeogenesis and inhibiting insulin and somatostatin produced absorption of glucose in increasing by GIT, pancreas, CNS the GIT. glycogenolysis. and somatomedins Release during stress. produced by liver. Cortisol (adrenal cortex) ACTH-adrenocorticotropic Stimulated by ACTH. hormone Increase blood glucose Release when cortisol glycogenolysis, level is low in the blood. gluconeogenesis, and Increase blood glucose lipolysis. level through glycogenolysis and Hormonal regulation of blood glucose level Human Placental Lactogen (HPL) produce by the placenta inhibits insulin activity Hormonal regulation of blood glucose level Any deficiency in the secretion of these hormones or destruction of endocrine glands responsible for its production can lead to abnormal blood glucose level Hormonal regulation of blood glucose level Increase blood sugar Decrease blood sugar 1. Glucagon 1. Insulin 2. Growth hormone 2. Somatomedins 3. ACTH 4. Thyroid hormone (thyroxine) 5. Epinephrine 6. Cortisol Abnormal blood glucose level Hyperglycemia Hypoglycemia 1.Diabetes mellitus (DM) 1.Overdose of insulin 2.Pancreatic deficiency 2.Hypothyroidism 3.Hyperadrenalism 3.Hypopituitarism (Cushing’s syndrome) 4.Hypoadrenalism 4.Excessive growth (Addison’s disease – hormone destruction of adrenal 5.Pheochromocytoma cortex) (tumor of the adrenal medulla) Glycemic diseases Glycemic diseases 1.Hyperglycemia (Diabetes mellitus) 2.Hypoglycemia 3.Glycogen storage diseases  Hyperglycemia (increase blood sugar) Diabetes mellitus A group of metabolic disorder with hyperglycemia as the hall mark of the disease. Due to: 1. Insulin secretion defects (insufficient insulin) 2. Impaired insulin action (insulin resistance) 3. Both Diabetes mellitus Signs and symptoms (3P’s) 1. Polyuria (excessive urination) 2. Polyphagia (excessive appetite) 3. Polydipsia (excessive thirst) Others symptoms Blurred vision, drowsiness, nausea, decreased endurance during exercise, slow healing wounds, and tingling or numbness in the feet. Diabetes mellitus complications (if left untreated) Microvascular Macrovascular 1.Diabetic 1.Circulatory retinopathy problems 2.Diabetic 2.Diabetic foot nephropathy 3.Diabetic neuropathy Microvascular complications Diabetic retinopathy Ophthalmic complications Swelling retinal blood vessels and leakage of fluid. Can lead to glaucoma and blindness. Glaucoma Glaucoma-damage in optic nerve due to high pressure in the eye. Microvascular complications Diabetic nephropathy Glomerular sclerosis (scarring). Thickening of the basement membrane resulting uremia and renal proteinuria. Uremia- high level of waste products in the blood such as urea and creatinine. Can lead to Chronic kidney disease (CKD). Test: Urine microalbumin and GFR. Microalbumin test Microvascular complications Diabetic neuropathy Peripheral nerve damage mostly the feet and legs. (numbness, tingling sensation, cramps, foot ulcers, bone and joint pain) MACROVASCULAR complications Circulatory problems. Loss of elasticity of blood vessels due to high blood sugar. Can lead to atherosclerosis. Heart attack Stroke MACROVASCULAR complications Diabetic foot Skeletal muscle damage Cellulitis- bacterial infection (Group A strep.) Osteomyelitis- infection of the bone. Classification of Diabetes mellitus Type 1 DM Type 2 DM Gestational DM Other specific type of DM Beta cells of Insulin resistance. Impaired insulin Genetic beta cells pancreas action due to defects destruction. hormonal changes Pancreatic during pregnancy. disease Endocrine disease Drug and chemical Insulin receptor abnormalities Oher genetic syndromes  Immune-mediated diabetes (type I) Insulin-dependent diabetes, type I diabetes, or juvenile-onset diabetes. 10-20% of the cases of DM. Autoimmune destruction of β- cells of the pancreas resulting to absolute insulin deficiency. Autoantibodies: β-cell include islet cell autoantibodies, autoantibodies to insulin, autoantibodies to glutamic acid decarboxylase (GAD) HLA genes can also be predisposing factors. Hyperglycemia and ketoacidosis. 3P’s, rapid weight loss, mental confusion, loss of consciousness and other complications of DM. Insulin resistance (Type 2 DM) Majority of cases of DM (90-95%). Referred to as non-insulin-dependent diabetes, type II diabetes, or adult-onset diabetes. Insulin resistance and usually have relative insulin deficiency. Most are obese, microvascular and macrovascular complications develop. Predisposing factors: genes, obesity, age, sedentary life style and nutrition. Less ketoacidosis. Treatment is hypoglycemic drugs (metformin). Women with prior GDM has a higher risk. Insulin resistance Cells of the muscle, liver, and fat are not responding to insulin thus glucose is not uptake into the cell to be used for energy production. Therefore lead to hyperglycemia. Cause: excessive production of insulin due to excessive eating. Resistance to insulin starts to manifest at the of 35 or 40 years old.  Type I vs Type II DM Type 1 Type 2 (absolute insulin (Insulin resistance) deficiency ) Age Mostly young ((juvenile) Mostly adult (>35 years old) Body structure Normal or thin Mostly obese Ketoacidosis (ketosis) Present Rare Prevalence Less (10 %) More prevalent (90 %) Treatment Insulin injection or IV Oral drugs (metformin) 3P’s Present Present Complications Macrovascular and Macrovascular and Note: Ketoacidosis refers microvascular microvascular to accumulation of ketones bodies in the blood such as Acetoacetate, β-Hydroxybutyrate and acetone produced from the beta oxidation of fatty acids (lipolysis). Gestational Diabetes mellitus (GDM) Gestational DM Development of glucose tolerance during pregnancy. Due to metabolic and hormones (HPL) Return to normal postpartum but has a higher risk of developing DM-2 later in life. Factors leading to GDM 1. Strong family history of DM 2. History of unexplained still birth 3. Obesity 4. Recurrent monilial (yeast) infections 5. Glycosuria Other specific type of DM (secondary) Other specific type of DM Genetic β cells defect Occurs at young age (before 25), characterized by insufficient insulin production. Autosomal inherited pattern, mutation in chromosome 12 (Hepatocyte nuclear factor) and chromosome 7 (glucokinase) these are glucose sensor. Dysfunction of glucose sensors can lead to insufficient insulin secretion therefore can lead to hyperglycemia. Other specific type of DM Other genetic diseases 1. Cystic fibrosis 2. Down’s syndrome 3. Klinefelter’s syndrome 4. Turner’s syndrome. Other specific type of DM Pancreatic disease Pancreatic carcinoma, pancreatitis, pancreatotomy, trauma or infection. Other specific type of DM Endocrine disease Acromegaly- growth hormones Cushing’s syndrome- cortisol Glucagonoma- glucagon Pheochromocytoma- epinephrine Thyroid diseases- Thyroxine These hormones inhibits the action of insulin. Other specific type of DM Drug- or chemical-induced diabetes Occurs in individual with prior insulin resistance. 1. Nicotinic acid 2. Glucocorticoids 3. α-interferon 4. Vacor (a rat poison) 5. Pentamidine Mechanism: affects insulin secretion and sensitivity, destruction of pancreatic cells or increased production of glucose. Other specific type of DM Insulin receptor deficiency (autoimmune disease) Production of anti-insulin receptor thereby blocking the binding of insulin to its receptor in target tissues. These autoantibodies are usually seen in SLE.  Hypoglycemia (decrease blood glucose level) Hypoglycemia Plasma glucose: 60-50 mg/dl (2.8-3.0 mmol/L) The body compensate: increase secretion of glucagon, epinephrine, cortisol, GH increases to raise the blood glucose level. Types Rapid fall of plasma glucose Triggers release of epinephrine which account for the following signs and symptoms attributed to hypoglycemia : weakness, shakiness, sweating, nausea rapid pulse, hunger and epigastric discomfort. Gradual fall in plasma glucose Not accompanied by epinephrine release; causes impairment of CNS function such as confusion, lethargy, seizure, and loss of consciousness. Hypoglycemia Causes a. Excessive pancreatic insulin b. Hypothyroidism c. Hypoadrenalism d. Von gierke’s disease (severe hepatomegaly due to deficiency of glucose-6-phosphate) Glycogen storage diseases Glycogen storage diseases Inherited metabolic disorder (rare). Commonly seen in infants and young children Deficiency in enzymes due to genetic cause. Impaired glucogenesis or glycogenolysis. Causes severe hypoglycemia, hepatomegaly and mental retardation. Glycogen storage disease Disease Enzyme defect Clinical feature Type I: Von Glucose -6-phosphate Hepatomegaly, hypoglycemia, Gierke dehydrogenase ketosis, hyperlipidemia (most common) Type II: Pompe Alpha 1.4 glucosidase Cardiorespiratory failure Type III: Cori Amylo-1-6 glucosidase Like type I but milder Type IV: Alpha 1-4 and alpha 1-6 Liver cirrhosis Andersen Type V: Mcardle Phosphorylase Limited physical activity due to muscle cramps Type VI: hers Phosophorylase Like type I but milder Type VII Phosphofructokinase Like type V Type VIII Phosphofructokinase Mild hepatomegaly and hypoglycemia Glycogen storage diseases Diagnosis Newborn screening (NBS) For early detection to provide clinical intervention thus minimizing signs and symptoms. Reference Bishop, Michael. 2018. Clinical Chemistry:Principles and Procedures, 8th ed. C and E Publishing Inc. Henry, John. 2002. Clinical Diagnosis and Management by Laboratory Methods, 22th ed. Merriam and Webster Inc. Tumamao, Aldrin. 2019. Clinical Chemistry Notes