MCAT Biochemistry
In glycolysis, one glucose molecule is broken into two molecules of pyruvate, generating two ATP (energy for cells) and two NADH molecules. Glycolysis can be considered as two halves: the investment phase (investment of energy) and the payoff phase (where energy is returned). Glycolysis occurs in the cytosol, with glucose molecules entering the cell membrane via GLUT membrane proteins. Hexokinase plays a crucial role at the beginning of glycolysis by phosphorylating glucose to form glucose-6-phosphate (G6P). Next, phosphoglucose isomerase transforms G6P into fructose-6-phosphate (F6P).
The key rate-determining step in glycolysis involves phosphofructokinase-1 (PFK-1), which adds another phosphate group to F6P, converting it to fructose-1,6-bisphosphate (F1,6BP). PFK-1 is regulated by allosteric inhibitors (ATP and citrate) as well as allosteric activators (AMP, ADP, and fructose-2,6-bisphosphate). Subsequently, aldolase cleaves F1,6BP into two three-carbon molecules: glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). Finally, triose phosphate isomerase turns DHAP into another G3P molecule, leaving two molecules of G3P for the next phase of glycolysis.
Lesson Outline
<ul> <li>Glycolysis: Investment Phase</li> <ul> <li>Introduction to glycolysis</li> <ul> <li>Purpose: breaking down 1 glucose into 2 pyruvate, 2 ATP, and 2 NADH</li> <li>Glycolysis located in the cytosol</li> </ul> <li>Step 1: Hexokinase phosphorylates glucose to make glucose-6-phosphate (G6P)</li> <ul> <li>ATP used to add phosphate group</li> <li>Irreversible</li> <li>G6P inhibits hexokinase via product inhibition</li> </ul> <li>Step 2: Phosphoglucose Isomerase converts G6P to fructose-6-phosphate (F6P)</li> <li>Step 3: Phosphofructokinase-1 (PFK-1) converts F6P to fructose-1,6-bisphosphate (F1,6BP)</li> <ul> <li>ATP used to add a phosphate group</li> <li>Irreversible</li> <li>Highly regulated: inhibited by ATP and citrate, activated by AMP/ADP and fructose-2,6-bisphosphate (F2,6BP)</li> </ul> <li>Step 4: Aldolase cuts F1,6BP into glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP)</li> <li>Step 5: Triose Phosphate Isomerase (TPI) converts DHAP into another G3P</li> <ul> <li>End of investment phase with 2 G3P molecules</li> <li>2 ATP invested</li> </ul> </ul> </ul>
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FAQs
Hexokinase is the enzyme responsible for catalyzing the first step in the investment phase of glycolysis. It phosphorylates glucose to form glucose-6-phosphate (G6P) by transferring a phosphate group from ATP to glucose. This reaction is irreversible and ensures that glucose is trapped within the cell, as well as activating it for further metabolism.
Glycolysis is a multistep process that converts glucose to pyruvate through a series of enzymatic reactions. The process occurs in two main phases: the investment phase and the payoff phase. During the investment phase, glucose is phosphorylated twice, generating fructose-1,6-bisphosphate (F1,6BP). The F1,6BP is then cleaved into two glyceraldehyde-3-phosphate (G3P) molecules. In the payoff phase, G3P is converted into pyruvate through a series of oxidation and phosphorylation reactions, producing ATP and NADH as well.
Phosphofructokinase-1 (PFK-1) is a key regulatory enzyme in the investment phase of glycolysis. It catalyzes the irreversible conversion of fructose-6-phosphate (F6P) into fructose-1,6-bisphosphate (F1,6BP) using a phosphate group from ATP. This reaction commits the glucose molecule to the glycolytic pathway, and PFK-1 activity is heavily regulated to control the rate of glycolysis based on the cellular energy demands and availability of substrates.
During the investment phase of glycolysis, ATP is consumed to phosphorylate glucose and fructose-6-phosphate, creating fructose-1,6-bisphosphate. In the payoff phase, each glyceraldehyde-3-phosphate (G3P) molecule generates 2 ATP as it is converted into pyruvate through multiple reactions, including the formation of 1,3-bisphosphoglycerate and PEP. Since two G3P molecules are formed for each initial glucose molecule, the net ATP production during glycolysis is 2 ATP per glucose.
NADH production during glycolysis is crucial for the efficient generation of cellular energy. In the glycolysis pathway, NAD+ is reduced to NADH when G3P is oxidized to 1,3-bisphosphoglycerate. NADH, as an electron carrier, can donate its electrons to the electron transport chain, fueling oxidative phosphorylation and producing additional ATP molecules. This makes NADH essential for maintaining a high-energy state in the cell.
