Glycolysis, Gluconeogenesis, and PPP (1D) - MCAT Biological and Biochemical Foundations of Living Systems

Net: $2$ ATP, $2$ NADH, $2$ pyruvate. Glycolysis converts glucose to pyruvate through a series of reactions that produce these molecules as net outputs for energy transfer and further oxidation.

Hexokinase (or glucokinase), PFK-$1$, pyruvate kinase. These enzymes catalyze steps with large negative free energy changes, making them irreversible and primary sites for pathway regulation.

Phosphofructokinase-$1$ (PFK-$1$). It catalyzes the slowest step in the pathway and is subject to extensive allosteric regulation based on cellular energy status.

PFK-$1$: fructose-$6$-P $ o$ fructose-$1,6$-bisP. This irreversible reaction, regulated by energy indicators, commits the substrate to the glycolytic pathway without reversal.

G3P dehydrogenase: G3P $ o$ 1,3-BPG + NADH. This oxidation-reduction step generates reducing power by transferring electrons from the substrate to NAD$^+$.

Fructose-$1,6$-bisphosphatase (FBPase-$1$). It hydrolyzes the phosphate group, providing a bypass for the irreversible phosphofructokinase-1 reaction in glycolysis.

Net: $2$ ATP (NADH is reoxidized by fermentation). Without oxygen, NADH cannot enter the electron transport chain, so fermentation recycles it without additional ATP production.

Fructose-$1,6$-bisphosphate (feed-forward activation). This upstream product enhances enzyme affinity for its substrate, promoting flux through the latter part of the pathway.

Pyruvate $ o$ acetyl-CoA (aerobic) or $ o$ lactate (anaerobic). Oxygen availability determines whether pyruvate is oxidized for energy or reduced to regenerate NAD$^+$ for anaerobic glycolysis.

Maintain blood glucose during fasting. It synthesizes glucose from non-carbohydrate precursors to prevent hypoglycemia when glycogen stores are depleted.

Glucose-$6$-phosphate (G6P). This early glycolytic intermediate can be diverted to the PPP for NADPH and pentose production when needed.

Activates PFK-$1$; inhibits FBPase-$1$. This molecule reciprocally regulates the opposing pathways to favor glycolysis or gluconeogenesis based on hormonal cues.

1,3-BPG $ o$ 3-PG and PEP $ o$ pyruvate. These reactions involve direct transfer of phosphate groups from high-energy intermediates to ADP, yielding ATP.

Lactate dehydrogenase. It catalyzes the reduction of pyruvate using NADH, thereby regenerating NAD$^+$ for continued glycolysis.

Regenerate NAD$^+$ to sustain glycolysis. Fermentation recycles NADH to NAD$^+$, preventing depletion that would halt glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step.

Activated by AMP and F-$2,6$-bisP; inhibited by ATP and citrate. These effectors modulate enzyme activity to accelerate glycolysis when energy is low or inhibit it when energy is abundant.

Consumes $4$ ATP + $2$ GTP + $2$ NADH. Energy input is required to drive the endergonic synthesis of glucose from pyruvate against the thermodynamic gradient.

Pyruvate carboxylase (biotin-dependent). Biotin serves as a cofactor for carboxyl group transfer, facilitating the ATP-dependent conversion to oxaloacetate.

Glucose-$6$-phosphate dehydrogenase (G6PD). It catalyzes the first committed step, regulated by the NADPH/NADP$^+$ ratio to control flux.

Generate NADPH and ribose-$5$-phosphate. The pathway provides reducing power for biosynthesis and pentoses for nucleotide synthesis.

Reductive biosynthesis and glutathione reduction (antioxidant defense). NADPH supplies electrons for anabolic reactions and maintains antioxidant systems by regenerating reduced glutathione.

Acetyl-CoA. It signals abundant energy from fatty acid oxidation, promoting the initiation of gluconeogenesis from pyruvate.

Maintain reduced glutathione (GSH) to detoxify peroxides. It regenerates GSH via glutathione reductase, enabling peroxide neutralization and protecting cells from oxidative damage.