glycolysis

Question 1

Define glycolysis

Answer 1

the set of reactions that oxidized glucose to lactate under anaerobic(10 steps) or pyruvate under aerobic conditions( 9 steps)

Question 2

Mention its site and subcellular site

Answer 2

Site:All the cells in the body
* Subcellular site: Cytosol

Question 3

.Describe the reactions in detail (aerobic and anaerobic- significance of lactate formation)

Answer 3

look at flow chart

Question 4

Explain substrate level phosphorylation with examples

Answer 4

-Synthesis of ATP coupled to the conversion of a substrate into product
- 1,3-biphosphoglycerate to 3-phosphoglycerate with phosphoglycerate kinase
- phosphoenopyruvate to pyruvate by pyruvate kinase

Question 5

Calculate the energetics of aerobic and anaerobic glycolysis

Answer 5

look at table
aerobic
Total ATP produced : 10
Total ATP used : 2
Net ATP produced : 8

anaerobic
Total ATP produced : 4
Total ATP used : 2
Net ATP produced : 2

Question 6

Compare aerobic and anaerobic glycolysis

Answer 6

Aerobic
-Supplies energy in presence of oxygen
- Occurs in all tissues with mitochondria
- Produces 2 pyruvates
- 8 ATPs per glucose

Anaerobic
-Supplies energy in absence/ lack of oxygen
-RBCs, WBCs, renal medulla, skin, testes, lens & cornea of the eye (poor blood supply or lack mitochondria), Muscle (during strenuous exercise)
-Produces 2 lactates
-2 ATPs per glucose

Question 7

Mention the significance of glycolysis(4)

Answer 7

• provide energy (only e source for RBC)
  -Rapoport-Luebering shunt
  1,3 bisphosphoglycerate → 2,3 bisphosphoglycerate (2,3BPG) (binds to hemoglobin which help in the release of O2 to tissues)
• synthesis of non-essential AA
  pyruvate undergoes transamination reaction to produce alanine
  -synthesis of triglyceride fats
  glycerol 3-phosphate for the synthesis of triglyceride

Question 8

Describe the significance of inhibitors(3)

Answer 8

1.Fluoride –Inhibits Enolase→Used to prevent Glycolysis in estimation of glucose
2. Pentavalent Arsenate – Competes with Pi for Glyceraldehyde 3-phosphate→No ATP generation
3. Iodoacetamide→Inhibit glyceraldehyde 3- phosphate dehydrogenase)

Question 9

Fluoride vacutainer (Grey)

Answer 9

• Used for collection of blood sample for glucose determination
• Contains Fluoride and EDTA (Ethylene diaminetetraacetic acid to prevents blood
  coagulation)
• Fluoride inhibits the glycolytic enzyme enolase non-competitively Inhibits the conversion of 2-phosphoglycerate to phosphoenolpyruvate Blocks glycolysis in RBCs Helps in accurate measurement of plasma glucose level.
• If fluoride is not used, RBCs will use up glucose in vitro leading to a false value of plasma glucose

Question 10

Explain the link between pyruvate kinase deficiency and hemolytic anemia

Answer 10

*Pyruvate kinase deficiency causing hemolytic anemia (disorder in which red blood cells are destroyed faster than they can be made)
* Effects are restricted to RBC
*  rate of glycolysis, depletion of ATP
* Loss of membrane integrity, loss of biconcave shape
* Such RBCs are destroyed by macrophages in spleen
* ↑ in 2,3 BPG, resulting in ↓ affinity of O2 for Hb, more O2 unloading

Question 11

Pyruvate kinase deficiency and hemolytic anemia

Answer 11

• Without this enzyme,RBC break down too easily, resulting in hemolytic anemia
• The RBCs use only glycolysis to generate energy ATP deficiency affects the NA+/K+ ATPase, leading to osmotic instability and deformed RBCs that are cleared in the spleen (extravascular hemolysis).
• Pyruvate kinase enzyme breaks down a chemical compound called adenosine triphosphate (ATP). Because this enzyme is deficient, there is a lack of ATP. The altered red blood cell has a shortened lifespan leading to hemolytic anemia.

Question 12

List the tissues exclusively dependent on glycolysis for energy production

Answer 12

• Brain
• RBC
• WBC
• Renalmedulla
• Lens & cornea of the eye
• testes

Question 13

Outline the regulation of glycolysis

Answer 13

look at slides

Question 14

Compare the properties and physiological roles of hexokinase and glucokinase

Answer 14

Hexokinases (I – III)
* Low Km for glucose ;allows efficient phosphorylation & metabolism of glucose even at low glucose levels
* LowVmax;donotphosphorylatemoresugarsthan the cell can use
Glucokinase (Hexokinase IV)
* High Km; functions only when cellular glucose level is very high (eg: in the hepatocytes after a meal)
* High Vmax; not saturated even at high glucose levels, is able to remove the flood of glucose delivered by portal blood following a meal
* Acts as a glucose sensor in b-cells of pancreas&
neurons of hypothalamus

Question 15

Hexokinases and Glucokinase

Answer 15

look at table

Question 16

Clinical correlation

Answer 16

Mutations that decrease activity of glucokinase cause maturity onset diabetes of the young type 2 (MODY 2)
* In MODY 2, -cells have show a higher threshold for glucose-stimulated insulin release; secrete insulin only at very high glucose levels

Question 17

Explain the steps and significance of
Rapoport
-
Luebering
shun

Answer 17

hemoglobin

Question 18

Explain the fate of pyruvate and lactate

Answer 18

look at slides 39n 40

Question 19

15. List the causes for lactic acidosis

Answer 19

• Lactic acidosis = occurs when lactic acid production exceeds lactic acid clearance/ Overproduction of lactic acid, high plasma lactate levels (anaerobic glycolysis)
• Cause:
• Decreased oxygen delivery
• Defect in mitochondrial oxygen utilization
• Collapse of circulatory system as in Myocardial
  infarction, pulmonary embolism & uncontrolled hemorrhage
  
  • Disturbs acid base balance– Metabolic acidosis

Question 20

Explain the clinical significance of lactate estimation in blood

Answer 20

• Detection of oxygen debt (during exercise, lactate production is high, which is utilized by liver to produce glucose. This process needs ATP – leads to increased oxygen consumption)
• Can be used to monitor recovery of patients from a period of oxygen deprivation