Glycolysis

the metabolic pathway of glucose oxidation and degradation, that has an .important energetical function a sequence of reactions that converts glucose into pyruvate with the concomitant production of ATP Glycolysis can be carried out anerobically (in the absence of oxygen) in this case 2 .molecules of ATP are obtained and pyruvate is converted in lactate Glycolysis can be carried out aerobically (in the presence of oxygen) in this case .pyruvate is converted in acetyl-CoA :has 2 stages I stage non-oxidative requires energy II stage oxidative produces energy The first stage of glycolysis (non-oxidative :(stage -:conversion of glucose into two .dihydroxyaceton-phosphate glyceraldehyde-3-phosphate .(The first stage of glycolysis (non-oxidative stage -:Reaction 1. The first reaction in glycolysis

-:Reaction 2. The second reaction in glycolysis

-: Reaction 3. The third reaction in glycolysis

-:Reaction 4. The forth reaction of glycolysis

-:Reaction 5. The other product of the reaction 4

-:The second stage of glycolysis (oxidative stage) energy generating stage two molecules of glyceraldehyde-3-phosphate are converted to pyruvate Result: 2 NADH+H+ and 4 ATP

Reaction 6. The two molecules of glyceraldehyde-3-phosphate are oxidized and .phosphorilated. NAD+ serving as the electron acceptor

Reaction 7. This is a reaction of substrate phosphrilation. The high energy potential of .1,3-bisphosphoglycerate is used to form ATP

Reaction 8. In this reaction a rearrangement of 3-phosphoglycerate to form 2.phosphoglycerate takes place

.(Reaction 9. Dehydration of 2-phosphoglycerate to form phosphoenolpyruvate (PEP

.Reaction 10. This is the second reaction of substrate phosphrilation

Glycolysis - total pathway: glucose + 2 NAD+ + 2 ADP + 2 Pi 2 pyruvate + 2 NADH + 2 .ATP :In aerobic conditions pyruvate produced in Glycolysis is converted in acetyl-CoA, that is oxidized to .CO2 in Krebs Cycle NADH produced in Glycolysis, Oxidative decarboxilation of pyruvate and Krebs Cycle is reoxidized in the respiratory chain, with production of much additional .ATP -:Energy production from glucose in aerobic conditions Total = 38 ATP

.In anaerobic conditions respiratory chain doesn't work In anaerobic conditions NADH is reoxidized by transferring the hydrogen to pyruvate, :yielding lactate

Entry of fructose into glycolysis:- Fructose enters glycolysis by two different pathways :depending on the tissue

-:Hereditary deficiencies of fructose metabolism Essential fructosuria deficiency of fructokinase the concentration of fructose increases .in the blood and urine .There are no other clinical manifestations or disabilities

Hereditary fructose intolerance:- results in an accumulation of fructose-1-phosphate in the liver, kidney, and small intestine inhibits glycogen breakdown and glucose synthesis, thereby .causing severe hypoglycemia Symptoms: severe abdominal pain, vomiting. Prolonged fructose ingestion in infants leads .ultimately to hepatic and/or renal failure and death -:Entry of galactose into glycolysis

-:Hereditary deficiencies of galactose metabolism -:Galactosemia galactose-1 phosphate uridyl transferase deficiency .1 deficiency of galactokinase-2 .deficiency of UDP-galactose-epimerase .3 disorders result in elevated levels of galactose in the blood mental retardation, eye and liver .abnormalities

-:Gluconeogenesis
..synthesis of glucose from non-carbohydrate precursors .the liver is the major site for glucose synthesis in animals .lactate, glycerol and some amino acids act as precursors The gluconeogenesis can be called a reverse glycolysis, but only seven of the ten reaction of glycolysis are reversible. Three reactions of glycolysis are irreversible .Hexokinase reaction:1 Glucose + ATP glucose-6-phosphate + ADP

:Phosphofructokinase reaction .3 Fructose-6-phosphate + ATP fructose-1,6-bisphosphate+ ADP :Pyruvate Kinase reaction .10 Phosphenolpyruvate + ADP Pyruvate + ATP -----------------------------------------------------------------------------------------------------------------:(Bypass 1 -bypass of pyruvate kinase reaction- pyruvate to phosphoenolpyruvate (PEP :Conversion of pyruvate to PEP requires two steps and two enzymes :Pyruvate Carboxylase catalyzes .1 pyruvate + CO2 + ATP oxaloacetate + ADP + Pi :PEP Carboxykinase catalyzes .2 oxaloacetate + GTP PEP + GDP + CO2. --------------------------------------------Bypass 2 -bypass of phosphofructikinase reaction- fructose-1,6-bisphosphate to fructose-6:phosphate :Fructose-1,6-bisphosphatase catalyzes a hydrolysis reaction fructose-1,6-bisphosphate + H2O fructose-6-phosphate + Pi ------------------------------------------:Bypass 3 -bypass of hexokinase reaction- glucose-6-phosphate to glucose :Glucose-6-phosphatase catalyzes an other hydrolysis reaction glucose-6-phosphate + H2O glucose + Pi ----------------------------------------Summary of Gluconeogenesis Pathway: Gluconeogenesis enzyme names in red Glycolysis .enzyme names in blue
glyceraldehyde-3-phosphate glucose NAD+ + P i Glyceraldehyde-3-phosphate P Dehydrogenase i NADH + H+

Glucon eogenesis

1,3-bisphosphoglycerate H2O glucose-6-phosphate ADP Phosphoglycerate Kinase Phosphoglucose Isomerase ATP 3-phosphoglycerate fructose-6-phosphate Phosphoglycerate Mutase Pi Fructose-1,6-bisphosphatase 2-phosphoglycerate HO
2

Glucose-6-phosphatase

Enolase fruct ose-1,6-bisphosphate H2O phosphoenolpyruvate Aldolase CO2 + GDP PEP Carboxykinase glyceraldehyde -3-phosphate+ dihydroxyacetonephosphate GTP Triosephosphate oxaloacetate -:Summary of Gluconeogenesis Pathway Pi + ADP HCO3 + ATP pyruvate Pyruvate Carboxylase Gluconeogenesis

(continued)

Isomerase pyruvate + 2 NADH + 4 ATP + 2 GTP 2 glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi

:The pentose phosphate pathway has two stages I stage - oxidative

II stage - non-oxidative

-: Glucose-6-phosphate Dehydrogenase.1

Phosphogluconolactonase catalyzes hydrolysis of the ester linkage, resulting in ring-6 .2 .opening. The product is 6-phosphogluconate -:Phosphogluconate Dehydrogenase .3

Epimerase .4 inter-converts stereoisomers ribulose-5-P and xylulose-5-P Isomerase .5 converts the ketose ribulose-5-P to the aldose ribose-5-P

.Ribose-5-phosphate is a substrate for synthesis of nucleotides and nucleic acids .NADPH functions as a reductant in anabolic (synthetic) pathways, e.g., fatty acid synthesis
2 N D A P glucose -6-P
+

2 N D A PH ribulose

+ CO 2 -5-P rib ose -5-P

fructose -6-P, & glyceraldehyde -3-P to G lycolysis for production of Pentose Phosphate Pathw producing ay N D A PH and A TP

AP T

Glyceraldehyde-3-P and fructose-6-P, formed from C sugar phosphates, may enter Glycolysis for ATP synthesis. The pathway also produces some-5 .NADPH -:Role of G6PD in red blood cells Diminished G6PD activity impairs the ability of the cell to form the NADPH that is essential for the maintenance of the reduced glutathione poo.l some patients with G6PD deficiency develop hemolytic anemia if they are treated with an oxidant .drug, ingest fava beans, or contract a severe infection -:Oxidant drugs Oxidant drugs: Commonly used drugs that produce hemolytic anemia in patients with G6PD .deficiency are best remembered from the mnemonic AAA = Antibiotics Favism, the hemolytic effect of ingesting fava beans, is not observed in all .individuals with G6PD deficiency, but all patients with favism have G6PD deficiency Infection: Infection is the most common precipitating factor of hemolysis in G6PD deficiency