Glycolysis (University Previous Year Question Paper)
? The metabolic pathway in which you breakdown glucose into two molecule of pyruvate by releasing energy as ATP and NADH.
? If there is oxygen and mitochondria available in cell then pyruvate ? Kreb's cycle (Aerobic Glycolysis).
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? If there is no mitochondria and O2 present in cell then pyruvate ? Lactic Acid (Anaerobic Glycolysis).
? Glycolysis take place in all cell of a body.
? Red blood cell have anaerobic glycolysis, no mitochondria present.
? If have high O2 but RBC does not utilized O2 to itself only transfer lung to tissue.
? Glycolysis is a cytosolic pathway.
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Transport of Glucose to cell:
- Glucose coming from GIT, it absorbed through the portal system into liver.
- Hepatocytes are specialized in extracting the glucose and store it so only small amount of glucose go to general circulation.
- So high level of Glucose stored in liver cell, so that in General circulation it does not produce Hyperglycemia.
- In Fasting stage, not high glucose passing through portal system, so liver cell are capable of releasing glucose back to circulation, so blood glucose level does not drop dangerously.
- Liver cell is bank of Glucose.
- Extra glucose ? captured, Less glucose ? released.
- Monosaccharides are Glucose, fructose and galactose so liver cell take the fructose and galactose convert them to glucose then pass to circulation.
- Glucose from blood goes into interstitial fluid then into cell.
- Glucose freely moves b/w blood and interstitial Fluid, same conc. in both.
- Cell is not permeable to large molecule of Glucose so cell have special type of transporter for Glucose.
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Glucose transport across cell
- High to low facilitated by GLUT.
- Facilitated diffusion.
- GLUT (14 types)
- No co-transporter
- GLUT 1 & 2 ? most of tissue, CNS or RBC high affinity.
- GLUT 4 ? skeletal M, adipose tissue. Dependent on insulin.
- GLUT 2 ? two way transporter. Liver, Kidney, ß cell of pancreas.
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Gluconeogenesis ? Formation of Glucose from non-carbohydrate (also in Kidney) so product.
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Glycogenesis ? Formation of glycogen.
Glycogenolysis ? glycogen is broken.
GLUT 5 ? Fructose transporter (GIT, Testes, sperm).
GLUT 7 ? Endoplasmic reticulum.
Glycolysis
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? ? ? Glucose transport in to cell by GLUT.
? ? ? Make Glucose highly polar by attaching phosphate to make it Polar (5-6 phosphate).
? ? ? Enzyme that capture and bind to phosphate by called Kinase (2 types Hexo and Glues to).
- Hexokinase slightly increase concentration, the power of reaction goes very rapidly up, upto plateau.
- Glucokinase little concentration it does not perform, and keep increase in concentration, it keep performing more.
- Most of the tissue have Hexokinase, have less amount of concentration, it Phosphorylated by it.
- Liver and some other have Glucokinase, because there is reuse high amount of concentration in cell.
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Add Phosphate ? Kinase
- Km of an enzyme: The concentration of a substrate at which half of the enzyme is saturated, and half is not.
- Vmax of an enzyme: all the concentration is saturated.
- Hexokinase have high affinity for concentration and Glucokinase have less affinity for concentration.
- Hexokinase slow Km and low Vmax.
- Glucokinase high Km and high Vmax.
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? ? ? G-6 phosphate little change in axion in Glucose molecule convert it into Fructose-6-phosphate by enzyme called.
Phospho Glucose Isomerase ? It is reversible.
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? Regulation of Hexo and Glues Kinase: Hexokinase and Glucosekinase is very well regulated enzyme.
- Hexokinase is inhibited by its product of reaction.
- Hexokinase are present in cytoplasm.
- Hexokinase active and if G-6 Phosphate ? hexo inactive.
- Glucokinase they are extremely well regulate.
- Glucokinase are present in Nucleus.
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- Glues Kinare regulating protein present in the nucleus of hepatocyte cell of liver where Glulase kinan binds.
- So concentration in liver cell is high, then Glucose goes into nucleus and pull out the Glucokinare in cyto, convert Glucose to G-6 Phosphate but G-6 Phosphate doesnot take Glueskineve back to nucleus to stop its activity if Fructose-6-Phosphate that pushed Glueskivare back into nucleus.
- Hexokinase is specific to Glucose and Galactose.
- Glucokinase is specific to Glucose.
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Glucokinare is specific to Glucose and Galactose.
? ? ? F-6-P to F-1,6-Bis Phosphate
Phospho Fructo Kinase enzyme ? one way reaction is well regulated enzyme.
Another enzyme which take back back real caved Fructos - 1,6 Bisphosphatase enzyme.
? If cell is in poor energy then Phosphorowels enzyme work to take reaction forward. to Produce energy.
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If cell is high in energy then Phospho Fructo 1 Bisphosphate enzyme work to take reaction backward and energy is consumed.
- Phospho Fructo Kinare it have multiple point where ATP, citrate and Amp attach to sense whats going on in the cell.
- Cell need energy, ATP less, citrate also less, Amp is very high mean cell is breakdown of ATP very bad level, then Chapho fructo Kinase become active. be Amp attached to it regulated.
- More ATP, Citrate, no Amp then cell does not need more energy it have enough energy then this enzyme become inactive regulated.
- Enzyme have certain pocket, due to changes in interaction with this pockets, this enzyme work, these type of enzyme called Allosteric regulation enzyme.
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ATP, citrate and AMP allosteric regulate the Phospho - Prudo Kinane - 1
- Phospho-huuto kinase-1 also regulated by Fructose -2,6- Bisphosphate it a very very strong ballosteric regulator. regulator.
- Fructose-phosphat also convert in Fructose, 2-6 Bisphoate when there is a million of Fructose bosphosphate prescut some of Hem convert into Fructos, 2-6 Bisphate. then reaction goes in forward direction. to so cett. then Fructose phosphate convert to Fructose 1-6 Bis phosphate.
- First small amount of Fructose-6-Phosphate convert to Fructose-2,6-Bisphosphate then it stimulate the phospho fructo Kina then Fructose-6-Phosphate convert to Fructose 1-6 Bis Phosphate.
Phospho Fructo Phosphatase Kinase is
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- F-2,6-Bis Phosphate (Hermephructiet enge?)
- The enzyme which convert F-6-P to F2-6 Bis Phosphate is double action Enzyme.
- Opposite action enzyme one component Phospho Fructo Kinase-2 (at 2nd position) add and component phosphatane It reverse the reaction by removing Phosphate.
How the Glucose level in blood determine Glycolysis?
- Glucose ? in blood Glycolysis ?, Glucose ? Glycolysis ?
- Glucose is low in blood Insulin ? Glucagon ?
- Glueagor high it stimulate receptor in cell and Glucose-stimulatory become active inside cell, then this stimulate Adenalyl cylane, then it convert ATP into & CAMP, then CAMP will stimulalo Protein Kinase A, then this become active.
- Then Prokein kinase A Phosphoryl the double actior enzyme, su enzyme kinase activity beran inactive avel phosphatase activity became active so Glycolysis stop.
- Glucose is high in blood insuline ? Glucagon ?
- The insuline stimulak protein phosphatane in the cell that remove phosphate from double actior azyme, then kinase activity become action Glycolysis forward.
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- F 2.6 Bis Phosphate stimulate PFK-1 and break down phosphatase activity.
- Some of the signal of insulin go into muitens and stimulale genes and then gene expresin are increases mear that genes are more transcor and mRNA prodwed, from that proleir produced.
- Some of there protein are Glucokinase and (Hexokinase), Phosphokautase kinase 1 also prodund these enzyme ave irreversible enzyme.
Insulin ? activate of enzyme Production of enzyme
Pyruvate Kin enzyme also prochured on insulin ? this is also irreversible enzyme.
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? Glucose F16 Bis Phosphate DHAP + Glyceral aldehyck 3 Phosphate
Aldolare enzyme cut F16 Bis Phosphate and make product
DHAP Dihydro acchine Phosphate at Glucose not same at Glucose Glyceraldehyde 3 Phosphate
It doesnut involve in Glycolysis so it convext into Glyceral aldehyde 3 Phosphate by enzyme called Triose Por isomexare
Glucose ATP ADP G-6-P this comes from ATP
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F6 Phosphate ATP ADP PFK-I F. 1.6 Bis Phosphate
? ? ? Glyceraldehyde 3- Phosphate Pi NAD 1,3-Bisphosphioglycera NADH + H
- Ir this reactior aldehyde group convert inle Carboxylic group and lot of energy released Some there enexgy is traped in form of NA and there also extra energy, this energy is traped by binding of phosphate to Carbor no. 1.
- The enzyme which involves in this 6xn called Glyceraldehyde 3 - Dehyclagenare this enzyme have three pocket carrying Phosphate, GA3 Phosphate, NAD+
- 2NADH ETC ATP indirectly produced.
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? ? 1,3-Bisphosphoglycerate 3-phosphoglycer remove ro Coubon no. 1 ADP ATP
- 2 ATP moleculer produced kom each side by removing Phosphate Foum substrate and add into ADP by the help of enzyme.
- The enzyme which convext called phospho Glycerate Kinase
Toxic drugs
Arsenic ? interfering enzyme function
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- G.A.3 Phosphate Dehydrogenan
- Pyruvate Dehydrogenase.
- Arsenic binds on GA3 Phosphate Dehydrogenase wheve inorganic Phosphate binds.
- So Glyceral aldehyde binds direelly convert 3 Phosphogluscerale without the step of 1,3 Bisphosphoglycerale, so there is no ATP and NADH formed.
GA3 Phosphate NAD NADH 13 Bis Phosphate Glucose ATP ADP ATP 3 Phosphate Glucose
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Arsenic
so glycolysis going or but energy not found
In Red blood cells
1,3-Bisphophoglycerate Mutase 2,3-DPG 2,3-Diphospho glycerate
- 2,3-DPG increare the capacity of hemoglobin to release oxygen.
- 2,3 DPG CROSS linked the 13 chain of HbA then Hb beame narrow to release more onyger to tissue.
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2,3 DPG 3 Phosphate Glucose
- ATP which is formed on by oxidative phosphorylat in Electron tramport chain
- ATP which formed in Glycolysis step 1,3 Bisglycerale 3 Phosphate Glycerate there ADP Convert to ATP, this type of phosphorylation called substrate level phosphorylation
? ? ? 3-phospho Glycerate phospho Glycerate Matase enzyme 2-phospho Glycerate
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phosphate change its position from C3 to C2.
? 10 ? 2-phosphonlycerate Enolase enzyme phosphoenol pyruvate H20
From 2 Phosphate Glucose we rentove H2O and louse the phosphate group, but not dead de altach it.
? phosphoend pyruvate pyruvate
- The enzyme called Pyruvate Kinase
- This is 3rd irreversible reaction. regulated
- pyruvate Kinane activated, by Fructose 1-6. Bis phosphate so it increare its reaction
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Glucose 1 Glucose pyruvate NAD ADP WAEP 2ADP 2NADH
Not ATP gain = 2ATP Put 2ATP and 2ATP out NADH = 2 mol. ATP
Net gain of ATP 8ATP
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Glycolysis (Anaerobic Glycolysis)
Erythroblast
Pyruvate Kinde
RBC do not have mitochonchia, So there is no ETC, abric cycle, so only get energy From Glycolysis.
- So there is conversion of NAD into NADH in Glycolysis but there is less amount of NAD present in RBC, So NADH utilized to formed NAD by the enzyme called lactate dehydrogenare which convert Pyruvate Into Lactate
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Pyruvate Lactate
So Glycolysis is working, there is not net gain in NADH.
- Net gain ATP = 2ATP
- Some of ATP utlized by the Natk pump ir ATP.
Hemolytic Anemia
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- The Pyruvate Kinase gene are mutant then it produced abnormal Pyruvate Kinase ir RBC PK are lens in concentration abnormal in function Laffinity for substrate, ? Umax. so the reaction become slow.
- So less ATP produced, pump Allare not work well then the RBCs shape Changes to spheric
it stuck into capillaries liver, where these eaten by macrophages, it cause the pre-mature hemolysis of RBC
Hemolytic Anemia Breakdown of RBC reduced RBCs count
Circunstance Anaerobic Glycolysis occur:
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Glycolysis
Anaerobic Gly Aerobic
normally RBCs, Leukocytes Renal medulla. Testes, lens
- mitochardia proant in
- have O2 in cell Cell
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invent JATP invent 2ATP
Recovery UATP Recovery YATP
Net NADHO net 2ATP
Net ATP ATP 2NADH ?GATP
Total net 18ATP
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- In Exercise, doing lot of work, hitizing more Oz cause deficiency of Oz it convext Pyruval to Lactate because NAOH accumulated in NADH ble ut less Oss so lactic auid accumulate in muscle cause cramp in muscle, lactic acid accumulation ? Elactic auclosis
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