Glycolysis Overview and Tissue Functions

Intended Learning Outcomes

• Students should be able to understand the key aspects of glycolysis by the end of the lecture.

Glycolysis

• Glycolysis is the oxidation of glucose to pyruvate, occurring in the presence of oxygen or resulting in lactate production in the absence of oxygen.
• The process occurs in the cytoplasm of all tissue cells.
• Glycolysis is crucial for tissues lacking mitochondria, such as mature Red Blood Cells (RBCs).

Glycolysis: Specific Tissue Functions

• RBCs: Exclusively rely on glycolysis for energy production.
• Skeletal Muscle: A primary energy source during high-intensity exercise.
• Adipose Tissue: Produces glycerol-P for Triglyceride (TG) synthesis and acetyl-CoA for Fatty Acid (FA) synthesis.
• Liver: Involved in acetyl-CoA production for FA synthesis and glycerol-P for TG synthesis.

ATP Yield in Glycolysis

• ATP calculation is based on ATP generated minus ATP utilized.
• Anaerobic glycolysis produces a net gain of 2 ATP.
• Aerobic glycolysis yields 8 ATP.

Glycolysis Pathway

• (Diagram needed here for accurate notes, but the provided text outlines the steps and enzymes involved.)*
• Glucose is phosphorylated to glucose-6-phosphate.
• Fructose-6-phosphate is phosphorylated to fructose-1,6-bisphosphate.
• The 6-carbon molecule fructose-1,6-bisphosphate is split into two 3-carbon molecules (glyceraldehyde-3-phosphate(G3P) and dihydroxyacetone phosphate(DHAP)).
• G3P is further metabolized to produce ATP and NADH.
• After a series of enzymatic reactions, pyruvate is formed.

Differences between Glucokinase and Hexokinase

Difference between Aerobic and Anaerobic Glycolysis

Biological Importance of Glycolysis

• Energy Production: Anaerobic glycolysis generates 2 ATP, while aerobic glycolysis yields 8 ATP.
• Oxygenation of Tissues: Formation of 2,3-bisphosphoglycerate decreases hemoglobin's affinity for oxygen.
• Intermediate Production: 3-phosphoglycerate is an intermediate, forming amino acid serine.
• Mitochondrial Fuel Source: Aerobic glycolysis provides pyruvate to the Krebs Cycle via the formation of acetyl CoA.

Fate of Pyruvate

• Anaerobic glycolysis: Pyruvate is reduced to lactate.
• Alcoholic fermentation: Pyruvate is converted to ethanol.
• Aerobic respiration: Pyruvate enters the Citric Acid Cycle (Krebs Cycle).

Fermentation

• Anaerobic organisms lack a respiratory chain.
• They oxidize NADH by reducing pyruvate to lactate or other more reduced compounds.
• Fermentation includes glycolysis plus the reoxidation of NADH.
• The process is needed to oxidize NADH in the absence of an electron transport chain.
• Pyruvate is the product in this process.

Lactate Dehydrogenase

• Lactate Dehydrogenase (LDH) catalyzes the reduction of pyruvate to lactate, oxidizing NADH to NAD+.
• Lactate is a mobile nutrient energy source and potential signaling molecule in mammals.
• Cells have carrier proteins to facilitate lactate transport.

Lactate Metabolism

• Lactate produced in active skeletal muscles can be released into the bloodstream and taken up by other tissues.
• Lactate can be converted back into pyruvate by LDH.
• Pyruvate can then enter the Krebs Cycle or be converted to glucose via gluconeogenesis in the liver.

Regulation of Glycolysis

• Glycolysis is controlled by 3 irreversible enzymes:
• Glucokinase/hexokinase
• Phosphofructokinase-1
• Pyruvate kinase.
• Insulin stimulates the last 3 enzymes, boosting glycolysis.
• Adrenaline and glucagon inhibit pyruvate kinase, limiting the process.
• G-6-P inhibits hexokinase(not glucokinase) while citrate inhibits phosphofructokinase.
• High/low levels of ATP,ADP and AMP can regulate the process.

Sources of Lactate

• Skeletal muscles, during high-intensity exercise which produces lactate,
• Astrocytes, which produce and release lactate in the brain. In RBCs, NAD+ regeneration converts pyruvate into lactate.

Lactate's Function

• Lactate is an end-product of fermentation.
• It's a mobile form of energy.
• Cell membranes contain carriers for lactate transport.
• Lactate in blood can be used by other cells or converted back to pyruvate.