Blood Glucose Lecture Notes PDF

Blood Glucose Blood sugar level means the concentration of glucose in blood. Normal blood glucose is from 80-120 mg % (per 100 ml blood or /dl) Lower value of glucose in blood is termed Hypoglycemia, and higher value of blood glucose is known as Hyperglycemia.  Extreme Hypoglycemia: (due to exce...

Blood Glucose Blood sugar level means the concentration of glucose in blood. Normal blood glucose is from 80-120 mg % (per 100 ml blood or /dl) Lower value of glucose in blood is termed Hypoglycemia, and higher value of blood glucose is known as Hyperglycemia.  Extreme Hypoglycemia: (due to excess insulin) cause unconsciousness – lowered blood pressure and death. (This is because the brain is highly dependent on glucose as an energy source), brain has no capacity for storing, and so depends on blood sugar Extreme Hyperglycemia: Due to the lack of insulin. The renal threshold is more than (180 mg %), normal =180 mg% and glucose appears in urine. Control of blood glucose: Synthesis and breakdown of glycogen is the most important process in control of blood glucose. Among the hormones controlling this level are: 1.Insulin. 2.Glucagon. 3.Adrenaline There major processes are involved and will be discussed in detail: Glycogenesis: Means the synthesis of glycogen from glucose. Glycogenolysis: Means the breakdown of glycogen into glucose. Gluconeogenesis: Means the synthesis of CHO from non-carbohydrate sources.  Glycolysis occurs in all human cells, where the glucose molecule is split up into two 3 carbon atoms compound called pyruvate. The small amount of energy produced by glycolysis is stored as ATP. Pyruvic acid produced in glycolysis have different fates depending on the organism and its metabolic status.  In anaerobic conditions: (absence of O2). -Pyruvate may be changed into one or more waste products (Lactate – ethanol and acetic acid). In aerobic conditions: (presence of O2). -The organism utilizes O2 as a terminal electron acceptor converting pyruvate to CO2 and H2O (aerobic respiration). * Glycolysis consists of 3 stages: A)Primary stage B) Splitting stage. C) Oxidoreduction stage The overall resulting equations in aerobic and anaerobic conditions are as follows: * Anaerobic : D. Glucose +2 ADP+2Pi 2 lactate +2 ATP. *Aerobic : D-Glucose +2 ADP +2 Pi+2 NAD+ 2 pyruvate+ 2ATP+2NADH+2H++2H2O. Major Pathways for Carbohydrate Metabolism  Primary Stage 1-Glucose is converted to Glucose -6- ph. Glucose (and other hexoses are immediately phosphorylate as they enter the cell. In most cells (except liver cells) glucose concentration is very low so Hexokinase will catalyze this 1st step. because it permits rapid action even at low intracellular concentration of glucose so its activity does not increase with higher glucose concentration. Note: ATP: Is a substrate in the reaction and complexes with Mg+2 in kinases reactions. Hexokinase : The enzyme which catalyzes the phosphorylation of glucose at the expense of ATP, the reaction is irreversible. In liver cells the major enzyme for phosphorylation is Glucokinase. Comparison between Glucokinase and hexokinase Hexokinase Glucokinase 1. present in all tissues Present in all liver cells. 1. inhibited strongly by glucose – 6- ph. i.e. Not in habited by glucose-6- (feed back inhibition) ph-but inhibited by fructose -6-ph. 1. Not affected by insulin or Diabetes. Synthesis induced by insulin and repressed by Diabetes. 1. Act on glucose –fructose and Galactose Act on glucose-only. 1. The enzyme level is not affected by Depends on glucose conc. fasting or high carbohydrate diet.  2-Glucose -6- ph is converted to fructose -6- ph. 1.The reaction is catalyzed by phosphoglucose isomerase This step is not regulated and is reversible. It is controlled by substrate – product levels. Enzyme may be known by phosphoexose isomerase.  3-Fr-6-ph is converted into Fr-1, 6 bis- phosphate. The reaction is catalyzed by phosphofructokinase (PFK-1) The reaction is regulated and is irreversible. PFK-1: This is the rate limiting enzyme and most important regulatory site of glycolysis. 1.The synthesis of PFK-1 increased by insulin and decreased by glucagons. The most active allosteric activator of this enzyme is fructose is fructose 2,6 bis- phosphate. 2.It is also allosterically activated by AMP, but inhibited by ATP. And by citrate. Regulation:- Q-How fructose 2,6 biphosphate formed under the effect of insulin ? And inhibited under the effect of glucagone and adrenaline ? B) Splitting Stage: 4-Fructose – 1,6 bis-phosphate is splitted into dihydroxy acetone phosphate (DHAP) and Glyceraldehyde 3- phosphate (Gly -3- ph.) The reaction is catalyzed by aldolase and is reversible. 5-Interconversion of Gly-3- ph. and DHAP is catalyzed by Triose phosphate isomerase enzyme – however the formation of Gly -3- ph. is favoured thus for each one molecule of glucose starting glycolysis, 2 moles of Glyceraldehyde -3-Ph. are produced. C) Oxidoreduction stage: 6-Glyceraldehyde -3-ph is converted into 1,3-diphosphoglyceric acid (1,3DPGA) The reaction is catalyzed by Gly-3-Ph dehydrogenase (Gly-3-ph-D). OR (triose –phosphate dehydrogenase). In this step :high energy phosphate bond is generated in 1,3 DPG. The enzyme binds NAD+ coenzyme. The enzyme has an – SH gp of cysteine at its active site In the presence of oxygen, the NADH resulting from this reaction is oxidized via the respiratory chain generating 3 ATP.  Iodoacetate : blocks the SH group at the active site of the enzyme glyceraldehyde -3- phosphate dehydrogenase, thus inhibiting glycolysis. Arsenate : replaces phosphate in the reaction catalyzed by this enzyme, inhibiting ATP donation in the subsequent step; it preventing substrate level phosphorylation and energy being liberated in the form of heat.  7-Conversion of 1,3 DPGA into 3 PGA: The reaction is catalyzed by phosphoglyceric acid kinase enzyme. This is the 1st step in glycolysis which produces ATP. Note : Till step (7) 2 ATP's were produced but used in steps (1,3 ) so the outcome of ATP until this step = zero. 8--Conversion of 3PGA into 2PGA: The reaction is catalysed by phosphoglucomutase enzyme and is reversible. Note 3PGA ( 2.3 DPGA) 2PGA. 2.3 DPGA is present in high concentration in RBC's because it regulates oxygen-Hb binding process. 9--Conversion of 2 PGA into phosphoenol pyruvate (PEP) The reaction is reversible. It generates a highly energetic cpd (PEP). * In this reaction.2PGA is dehydrated (-H2O), forming (PEP), this reaction is catalyzed by enolase. Glycolysis can be inhibited in vitro by floride ,fluorides inhibit enolase by forming (Mg-fluorophosphate), which blocks the active site of the enzyme. Note:- Fluorides are added to blood samples collected for measuring blood glucose to prevent glycolysis, which lowers the blood glucose 10-Conversion of PEP to Pyruvate: It is catalysed by Pyruvate kinase and is irreversible. Two molecules of ATP are formed for each molecule of glucose. Pyruvate kinase: Synthesis of this enzyme is stimulated by insulin. and inhibited by glucagon. PK.b (inactive form) or phosphorylated form occur on serine residues in the enzyme, and this reaction is catalyzed by protein kinase A. Regulation:- 11-Conversion of Pyruvate to Lactate: The reaction is catalyzed by lactate dehydrogenase (LDH) in anaerobic conditions : (reaction is reversible)  Calculation of energy production from glycolysis (Aerobic – Anaerobic) Aerobic Anaerobic 1. Hexokinase -1 ATP -1 ATP 1. Phosphofructo kinase-1 (PFK- -1 ATP -1 ATP 1) 1. Glyceraldehyde - 3 ph - + 6 ATP ---- dehydrogenase (2NADH, H+) respiratory chain( ETC) 1. phosphoglyceric acid kinase +2ATP +2ATP 1. pyruvate kinase +2 ATP +2 ATP Tatal ATP's = 8ATP 2ATP  12-Conversion of Pyruvic to Ethanol: Yeast and microorganisms can convert pyruvic acid to acetaldehyde in a reaction catalyzed by pyruuvate decarboxylase relasing CO2 (in yeast). 13-Acetaldehyde is converted by alcohol dehydrogenase enzyme into ethanol in presence of NADH, thus regenerating NAD+. Note1: In step no. (11) of glycolysis. *Formation of Lactate:- Under anaerobic conditions, the NADH (formed in step 6) gives its hydrogen to the ketopyruvate (pyruvate), converting it into lactate; the reaction is catalyzed by Lactate dehydrogenase (LD). This reaction regenerates oxidized NAD+ in the absence of oxygen, thus, allowing step 6, and glycolysis to proceed.  So for reaction 6 ,glycolysis would haven't stopped in absence of oxygen due to conversion of all NAD+ in the cytosol into NADH ,but still occur due generate of oxidized NAD+ in step11 in absence of O2 In Respiratory and circulatory failure (shock, hemorrhage, and pulmonary embolism) lead to tissue hypoxia. Glycolysis becomes the main source of ATP and ends in the formation of lactic acid. This produces marked elevation of the level of lactic acid in the blood, which leads to acidosis; condition called Lactic acidosis