Glycolysis, Gluconeogenesis, and PPP (1D) - Bio & Biochem

What is the purpose of fermentation in human cells during anaerobic glycolysis?

Regenerate NAD $^+$ to sustain glycolysis. Fermentation recycles NADH to NAD $^+$ , preventing depletion that would halt glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step.
What is the rate-limiting enzyme of the PPP oxidative phase?

Glucose- $6$ -phosphate dehydrogenase (G6PD). It catalyzes the first committed step, regulated by the NADPH/NADP $^+$ ratio to control flux.
What is the rate-limiting enzyme of glycolysis?

Phosphofructokinase- $1$ (PFK- $1$ ). It catalyzes the slowest step in the pathway and is subject to extensive allosteric regulation based on cellular energy status.
Which glycolysis steps generate ATP by substrate-level phosphorylation?

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.
Which tissues are the principal sites of gluconeogenesis?

Liver (major) and kidney cortex (important in prolonged fasting). These organs express the necessary enzymes and can release glucose into circulation to support systemic needs.
What are the key allosteric regulators of PFK- $1$ (activators and inhibitors)?

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.
What molecule allosterically activates pyruvate carboxylase?

Acetyl-CoA. It signals abundant energy from fatty acid oxidation, promoting the initiation of gluconeogenesis from pyruvate.
Which glycolysis step produces NADH, and what is the enzyme?

G3P dehydrogenase: G3P $ o$ 1,3-BPG + NADH. This oxidation-reduction step generates reducing power by transferring electrons from the substrate to NAD $^+$ .
Which gluconeogenesis enzyme requires biotin and uses ATP to carboxylate pyruvate?

Pyruvate carboxylase (biotin-dependent). Biotin serves as a cofactor for carboxyl group transfer, facilitating the ATP-dependent conversion to oxaloacetate.
What are the main cellular uses of NADPH produced by the PPP?

Reductive biosynthesis and glutathione reduction (antioxidant defense). NADPH supplies electrons for anabolic reactions and maintains antioxidant systems by regenerating reduced glutathione.
What enzyme converts fructose- $1,6$ -bisphosphate to fructose- $6$ -phosphate in gluconeogenesis?

Fructose- $1,6$ -bisphosphatase (FBPase- $1$ ). It hydrolyzes the phosphate group, providing a bypass for the irreversible phosphofructokinase-1 reaction in glycolysis.
What molecule allosterically activates pyruvate kinase in glycolysis?

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.
What is the net energy cost to form 1 glucose from 2 pyruvate in gluconeogenesis?

Consumes $4$ ATP + $2$ GTP + $2$ NADH. Energy input is required to drive the endergonic synthesis of glucose from pyruvate against the thermodynamic gradient.
What is the primary function of the pentose phosphate pathway (PPP)?

Generate NADPH and ribose- $5$ -phosphate. The pathway provides reducing power for biosynthesis and pentoses for nucleotide synthesis.
What are the three irreversible (regulated) enzymes of glycolysis?

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.
Which glycolysis intermediate is the substrate that enters the PPP, and what is it called?

Glucose- $6$ -phosphate (G6P). This early glycolytic intermediate can be diverted to the PPP for NADPH and pentose production when needed.
What is the net ATP yield of glycolysis per 1 glucose under anaerobic conditions?

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.
What is the primary physiologic role of gluconeogenesis?

Maintain blood glucose during fasting. It synthesizes glucose from non-carbohydrate precursors to prevent hypoglycemia when glycogen stores are depleted.
What enzyme converts pyruvate to lactate and regenerates NAD $^+$ in anaerobic muscle?

Lactate dehydrogenase. It catalyzes the reduction of pyruvate using NADH, thereby regenerating NAD $^+$ for continued glycolysis.
What is the net yield of glycolysis per 1 glucose under aerobic conditions?

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.
Identify the direct effect of fructose- $2,6$ -bisphosphate on glycolysis vs gluconeogenesis.

Activates PFK- $1$ ; inhibits FBPase- $1$ . This molecule reciprocally regulates the opposing pathways to favor glycolysis or gluconeogenesis based on hormonal cues.
What is the key antioxidant role of NADPH in red blood cells?

Maintain reduced glutathione (GSH) to detoxify peroxides. It regenerates GSH via glutathione reductase, enabling peroxide neutralization and protecting cells from oxidative damage.
What are the two major fates of pyruvate in human metabolism (excluding gluconeogenesis)?

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.
What glycolysis step commits glucose to glycolysis and is strongly regulated?

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.

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