Reactions Of Glycolysis Parts 1 And 2 Flashcards
What is glycolysis ?
• One of the principal pathways for generating ATP (energy)
• In brain (fed and fasted state), liver and tissues that lack mitochondria
or oxygen
- Glycolysis can generate ATP in the presence and absence of O2 (aerobic and anaerobic) and in the presence and absence of mitochondria
- Glycolytic enzymes are present in the cytosol
- Glycolysis is the sole provider of energy (ATP) in tissues that do NOT have mitochondria (RBCs, tissues of the eye)
What is the energy investment phase of glycolysis?
- This stage is characterized by two phosphorylation reactions that require ATP (energy investment phase) – requires 2 ATP
- PFK-1 is the second irreversible reaction of glycolysis and also the most important regulated step (allosteric regulated enzyme)
Describe the cleavage of 6C sugar into 3C intermediates
- Aldolase cleaves fructose 1,6 bisphosphate into two trioses (3C) glyceraldehyde 3 phosphate and dihydroxyacetone phosphate. Aldolase A is present in muscle and Aldolase B in liver. Aldolase B is also required for metabolism of fructose.
- The isomerase converts the dihydroxyacetone phosphate to glyceraldehyde 3- phosphate to enable it to be further metabolized by glycolysis
• Glucose is cleaved to two molecules of glyceraldehyde 3-phosphate;
Remember: all reactions from now on occur twice to form two molecules of
pyruvate
What are the reactions of the energy generation phase?
• Glyceraldehyde 3-phosphate dehydrogenase
results in the formation of an NADH
- Phosphoglycerate kinase results in the formation of the first ATP (substrate level phosphorylation)
- 1,3-BPG is a high energy intermediate that results in the formation of ATP without involving the mitochondrial electron transport chain (ETC)
- Remember substrate level phosphorylation reactions are important during periods of low oxygen (hypoxia)
- All 3 reactions listed on this slide are reversible
What is the significance of the energy generation phase?
- Phosphoenolpyruvate is a high energy compound that results in the formation of ATP, without the involvement of the ETC in mitochondria (substrate level phosphorylation)
- Remember substrate level phosphorylation reactions are important during periods of low oxygen (hypoxia)
- Pyruvate kinase results in the formation of the 2nd ATP
- Pyruvate kinase is an irreversible reaction
- From a molecule of glucose (6C), 2 molecules of pyruvate (3C) are formed as a result of glycolysis
What are the fates of pyruvate?
aerobic- Acetyl CoA
AnAerobic- lactate
Oxaloacetate
What is the Fate of puyruvate under anaeobic condtions?
- Pyruvate formed in glycolysis is metabolized anaerobically in the absence of mitochondria or poorly vascularized tissues (red blood cells, lens, cornea, leukocytes) and in conditions where there is a lack of oxygen (actively contracting white skeletal muscle, cardiac muscle hypoxia) to lactate (lactic acid)
- The NADH formed by the glyceraldehyde 3-phosphate dehydrogenase reaction is reoxidized to form NAD+. This allows glycolysis to proceed even in the absence of mitochondria
- LDH is a cytosolic enzyme Five tissue specific isoenzymes are present (ref: Enzymes)
- The direction of the reaction depends on the NADH /NAD+ ratio. Higher the NADH levels, the reaction is driven towards lactate formation
• Identify states that result in high NADH/NAD+ ratio
What is the fate of lactate formed under anaerobuc cinditions in muscle?
- In an actively contracting skeletal muscle, NADH formed as a result of glycolysis and TCA cycle, exceed the oxidative capacity of the ETC, resulting in a high NADH/NAD+ ratio. This favors the conversion of pyruvate to lactate via lactate dehydrogenase; Lactate levels in blood increase following exercise
- Lactate accumulation in muscle causes a drop in pH and may manifest as cramps during intense exercise;
- Lactate formed in skeletal muscle and red blood cells, eventually diffuses out of the cells and is taken to the liver where it is used for gluconeogenesis (Cori cycle)
- Cardiac muscle has a low NADH/ NAD+ ratio and is predominantly aerobic (due to abundance of mitochondria and good vascularization). Heart muscle converts lactate to pyruvate and later to acetyl CoA, to enable it to enter the TCA cycle. Cardiac muscle hypoxia may result in lactate formation (myocardial infarction).
What are the key Features of glycolysis?
- Oxidation of glucose to 2 molecules of pyruvate
- Cytosolic pathway
- Three irreversible reactions (regulatory steps) • Glucokinase/ hexokinase
- Phosphofructokinase-1
- Pyruvate kinase
- Two substrate level phosphorylation reactions (ATP formed)
- Phosphoglycerate kinase • Pyruvate kinase
- Fate of pyruvate
• Aerobic: Pyruvate is transported to mitochondria and
conversion to acetyl CoA (pyruvate dehydrogenase)
• Anaerobic: Pyruvate is converted to lactate in cytosol (lactate dehydrogenase)
What are the energetics of glycolysis under aerobic conditions?
- Overall reaction (aerobic)
- Glucose→2 molecules of Pyruvate
- 2 NADH+ H+ (formed in glyceraldehyde 3-phosphate dehydrogenase reaction) = 2x3 = 6 ATP (or 2.5 ATP per NADH)
- NADH formed in the cytosol by glycolysis is transported into the mitochondria by the shuttle systems (malate-aspartate or glycerol- phosphate shuttle)
- 4 ATP (formed in the substrate level phosphorylation reactions) (2ATP from each mol of glyceraldehyde 3 phosphate)
- -2ATP used in the energy investment phase
- Total = 8 ATP (Aerobic glycolysis)
Describe the energetics of glycolysus under anaerobic conditions
• Overall reaction (anaerobic)
- Glucose→2 molecules of Lactate
- 2 NADH+ H+ (formed in glyceraldehyde 3 phosphate dehydrogenase reaction) are used in lactate dehydrogenase reaction – No Net ATP from NADH when conditions are anaerobic
• 4 ATP (formed in the substrate level phosphorylation reactions) (2ATP from each mol of glyceraldehyde 3 phosphate)
- -2ATP used in the energy investment phase
- Total = 2 ATP (Anaerobic glycolysis)
- ATP (energy) yield is always lower when conditions are anaerobic!!!!
- Glycolysis is the sole source of energy when tissues are hypoxic and in tissues with no mitochondria!!
Summarize features of glycolysis under aeribic conditions
- Tissues: Brain, liver, heart
- Energy yield: 8 ATP
- End product: Pyruvate
- Further fate of pyruvate: Converted to acetyl CoA by PDH complex
- Fate of NADH formed: Enters ETC (mitochondria) to form 3(or 2.5) ATP per NADH
Summaruze glycolysis under anaerobic conditions
- Tissues: RBC, Retina, lens, actively contracting skeletal muscle (Tissues which lack mitochondria or oxygen) or hypoxic tissues
- Energy yield: 2 ATP
- Endproduct:Lactate
• Further fate of pyruvate: Converted to lactate by lactate dehydrogenase
• Fate of NADH formed: Used in the reduction of pyruvate to lactate by
lactate dehydrogenase
