Glucose in blood Seminar No. 3 - Chapter 8 - What is glucose? * the most common monosaccharide, aldohexose [* ] C[6]H[12]O[6] (M[r] 180) * grape sugar, blood sugar, dextrose * the most important sugar in the human body * the source of chemical energy (17 kJ/g) * metabolic nutrient for most tissues * prominent fuel for the brain and RBC Different formulas of D-glucose A = D-glucose (Fischer formula) B = b-D-glucopyranose (Fischer formula) C = b-D-glucopyranose (Haworth formula) D = a-D-glucopyranose (chair conformation) E = b-D-glucopyranose (chair conformation) Sources of glucose in blood * Resorption phase = just after meal Exogenous saccharides (food) * Postresorption phase = in the obvious fasting Endogenous storage and/or non-saccharide precursors of Glc Glucose sources in resorption phase * Starch (polysaccharide from glucose: amylose + amylopectin) Starch-based food: cereals, bread, rolls, pastry, cakes, biscuits, dumplings, rice, pasta, semolina, legumes, potatoes, banana * Sugar (table sugar, sucrose, disaccharide: glucose + fructose) commercially available in 100% purity ----------------------------------------------------------------------------- * Lactose (disaccharide: galactose + glucose) -- milk * Glucose -- free glucose is very rare in common food * Fructose -- fresh fruits (5-10 %), honey (cca 60 %) * Honey ~= 30 % glucose, 60 % fructose, 10 % sucrose Starch content in some food Free glucose is rare in food Glucose sources in postresorption phase * Liver glycogen is degraded by phosphate (phosphorolysis) * Gluconeogenesis from non-saccharide substrates: Lactate (60 %) Alanine (30 %) Glycerol (10 %) Five stages of glucose homeostasis Five stages of glucose homeostasis * Stage I -- glucose comes from food (mainly starch) * Stage II -- glycogenolysis in liver * Stage III -- gluconeogenesis in liver starts to work * Stage IV -- in addition to liver, kidney starts to make Glc * Stage V -- liver and kidney gluconeogenesis diminishes, energy needs of most tissues are met by FA + KB Q. 1 (p. 45) What is reference range of glucose concentration in blood? A. 1 3.3 -- 5.6 mmol/l capillary blood Transport of glucose into cells * Glucose is highly polar compound, does not pass freely across hydrophobic cell membranes * Requires specific protein transporters * GLUT = glucose transporter Insulin-independent transporters * In most tissues (liver, CNS, Ery) * Passive transport -- facilitated diffusion * Transporter -- integral protein * After binding Glc it changes conformation and releases glucose into ICF Insulin-dependent transporters * In muscles, adipose tissue -- peripheral tissues * After binding Glc it changes conformation and releases glucose into ICF * Free transporters are then transferred inside the cell by endocytosis * Insulin stimulates their incorporation into cell membrane when necessary Symport (co-transport) with Na^+ ions * In enterocytes, renal tubules * Transporter binds together Glc and Na^+ * Na^+ ions move from high conc. space to low conc. space * Glc remains in cell and it is metabolized * Na^+ ions are expelled from cell via Na^+,K^+-ATPase pump Symport of Glucose with Na^+ Hormonal regulation of Glc metabolism * "Resting state" hormones: insulin, glucagon * Stress hormones: adrenalin, cortisol Insulin (after meal) * High blood glucose level is the signal for insulin secretion * Stimulates glycolysis in liver, muscles and other tissues * Increases glucose transport into adipose tissues and muscles * Stimulates synthesis of glycogen, TAG, proteins Glucagon (after meal) * Antagonist of insulin * Low blood glucose level is the signal for glucagon secretion * Stimulates breakdown of glycogen in liver (not in muscles) * Stimulates gluconeogenesis from aminoacids Adrenaline (in stress) * Signal that energy is needed immediately * Very quick action * Stimulates the breakdown of glycogen (in liver and muscles) and TAG Processes in resorption phase (insulin) Processes in postresorption phase (glucagon) Q. (p. 42) The important intermediate of Glc is Glc-6-phosphate. What enzymes catalyze its formation? A. hexokinase glucokinase Glc + ATP (r) Glc-6-P + ADP Q. (p. 42) What enzyme catalyzes the conversion of Glc-6-P to glucose? In which organs is it located? A. glucose-6-phosphatase Glc-6-P + H[2]O (r) Glc + P[i ] occurs in liver, kidney, intestine but not in muscles ^ Metabolic Features of Diabetes (IDDM) see the scheme on the page 43 metabolic processes occur under influence of glucagon Metabolic Features of Diabetes (IDDM) * The lack of insulin TH Glc cannot enter adipose and muscle cells TH elevated blood Glc * The release of glucagon TH glycogenolysis + lipolysis TH elevated blood glucose + elevated blood FA * The excess of FA TH excess of acetyl-CoA (over CAC capacity) TH synthesis of KB TH elevated blood KB * Limited glycolysis in liver TH not enough pyruvate TH not enough oxaloacetate to run CAC TH excess of acetyl-CoA (over CAC capacity) TH synthesis of KB TH elevated blood KB * The lack of insulin TH not enough LPL (insulin is inductor of its synthesis) TH elevated blood CM + VLDL The metabolic consequences of insuline << glucagon ratio The metabolic consequences of insuline << glucagon ratio Complications of diabetes Acute * ketoacidosis (pH of blood < 7.36) * hyperosmolarity of blood plasma (> 310 mmol/l) Long-term * non-enzymatic glycation of proteins * AGE production (advanced glycation endproducts) * activation of sorbitol (glucitol) production Glycated hemoglobin HbA[1c ]* it is formed non-enzymatically in RBC * reaction of globin NH[2]-terminal group with aldehyde group of glucose * the concentration of HbA[1c] depends on: concentration of glucose in blood duration of hyperglycemia concentration of hemoglobin (less important factor) * normal values: 6-8 % * the value of HBA[1c] gives cumulative information on glucose level in recent 6-8 weeks Glycation of proteins Glycation of proteins Determination of Glc in body fluids Personal glucometer (you will see in the labs) Three diabetics, supervised after 6 weeks (p. 44) Patient No. 1 (left picture) glucose level .......................... little elevated HbA[1] .................................... OK conclusion .............................. good dietary regime Patient No. 2 (middle picture) glucose level .......................... OK HbA[1] .................................... significantly elevated conclusion .............................. bad dietary regime Patient No. 3 (right picture) glucose level .......................... OK HbA[1] .................................... little elevated conclusion .............................. acceptable dietary regime