Glycolysis, Pyruvate Fate, PPP, TCA, ETC & Metabolic Regulation (Page 1 Notes)

Vocabulary flashcards covering glycolysis, pyruvate fate, PPP, TCA, ETC, and metabolic regulation topics from Page 1 notes.

Glycolysis overall reaction

Glucose + 2 NAD⁺ + 2 ADP + 2 Pi → 2 pyruvate + 2 NADH + 2 ATP + 2 H₂O + 2 H⁺

Hexokinase

Phosphorylates glucose to glucose-6-phosphate; first step of glycolysis; consumes one ATP; irreversible in muscle (glucokinase in liver)

Phosphoglucose isomerase

Isomerizes glucose-6-phosphate to fructose-6-phosphate in glycolysis

Phosphofructokinase-1 (PFK-1)

Rate-limiting, irreversible enzyme converting fructose-6-phosphate to fructose-1,6-bisphosphate; major control point in glycolysis

Aldolase

Cleaves fructose-1,6-bisphosphate into two three-carbon sugars (DHAP and GAP) in glycolysis

Triose phosphate isomerase

interconverts dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP)

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Oxidizes GAP to 1,3-bisphosphoglycerate and reduces NAD⁺ to NADH; NADH produced in glycolysis

Phosphoglycerate kinase

Generates ATP and 3-phosphoglycerate from 1,3-bisphosphoglycerate in glycolysis; substrate-level phosphorylation

Phosphoglycerate mutase

Rearranges 3-phosphoglycerate to 2-phosphoglycerate in glycolysis

Enolase

Dehydrates 2-phosphoglycerate to phosphoenolpyruvate (PEP) in glycolysis

Pyruvate kinase

Catalyzes the final step of glycolysis converting PEP to pyruvate with ATP generation; irreversible

ATP consumption in glycolysis

Consumption steps: Hexokinase (glucokinase in liver) and PFK-1 consume ATP early in glycolysis

ATP production in glycolysis

Production steps: Phosphoglycerate kinase and Pyruvate kinase generate ATP (substrate-level phosphorylation)

Glycolysis regulation targets

Key control enzymes: Hexokinase, PFK-1, and Pyruvate kinase regulate flux through glycolysis

NADH production in glycolysis

Occurs at the GAPDH step when GAP is converted to 1,3-bisphosphoglycerate

Pyruvate under aerobic conditions

Pyruvate is converted to acetyl-CoA by the pyruvate dehydrogenase complex (PDH) and enters the TCA cycle

Pyruvate under anaerobic conditions

Pyruvate is reduced to lactate by lactate dehydrogenase, regenerating NAD⁺ for glycolysis

NAD⁺ regeneration importance

Regenerates NAD⁺ to allow continued glycolysis, particularly the GAPDH step

Cytosolic NADH transfer to mitochondria

NADH is shuttled into mitochondria via the glycerol-3-phosphate shuttle or the malate–aspartate shuttle

NADH oxidation in mitochondria

Electrons from NADH enter the electron transport chain, passing through Complex I to Q, Complex III, cytochrome c, Complex IV and ultimately O₂

Proton pumping and ATP synthesis

Proton pumping across the inner mitochondrial membrane creates a proton motive force that drives ATP synthase to make ATP

P/O ratio

Approximately 2.5 ATP per NADH and 1.5 ATP per FADH₂ oxidized in the electron transport chain

Lactate production tissues under hypoxia

RBCs, exercising muscle, retina, skin, and renal medulla

Cori cycle

Lactate from muscle travels to liver, is converted to glucose, and returns to muscle

3-phosphoglycerate role

A glycolytic intermediate that can be diverted to serine biosynthesis

2,3-Bisphosphoglycerate (2,3-BPG)

Made from 1,3-bisphosphoglycerate by bisphosphoglycerate mutase; modulates hemoglobin O₂ affinity

Glycolytic intermediates to lipids or amino acids

DHAP → glycerol-3-phosphate for triglycerides; pyruvate/PEP → amino acids (e.g., alanine)

Regulation by energy status (PFK-1)

ATP and citrate inhibit PFK-1; AMP activates PFK-1 to stimulate glycolysis

Fructose-2,6-bisphosphate (F-2,6-BP)

Activates PFK-1 and inhibits FBPase-1, promoting glycolysis over gluconeogenesis

Glycolysis: muscle vs liver regulation

Muscle: regulated by energy charge (AMP/ATP); Liver: regulated by hormones via F-2,6-BP to coordinate with gluconeogenesis

Glycogenolysis enzymes

Glycogen phosphorylase, debranching enzyme, and phosphoglucomutase regulate glycogen breakdown

Hormonal regulation of glycogen phosphorylase

Glucagon (liver) and epinephrine (muscle) activate via cAMP/PKA signaling to promote glycogenolysis

Glycogen breakdown: liver vs muscle

Liver maintains blood glucose; muscle uses it locally to provide ATP and does not export glucose

Pentose phosphate pathway (PPP) functions

Produces NADPH for biosynthesis and ribose-5-phosphate for nucleotide synthesis

G6PD deficiency

Glucose-6-phosphate dehydrogenase deficiency causes hemolytic anemia due to reduced NADPH production in PPP

PPP in biosynthesis

NADPH supplies reducing power for fatty acid and cholesterol synthesis; ribose-5-phosphate for nucleotide synthesis

TCA cycle yield per acetyl-CoA

3 NADH, 1 FADH₂, 1 GTP, and 2 CO₂ are produced per acetyl-CoA entering the cycle

Anaplerotic reaction

Replenishes TCA cycle intermediates; e.g., pyruvate → oxaloacetate via pyruvate carboxylase

Cataplerotic reaction

Removes TCA cycle intermediates for biosynthesis; e.g., citrate export to fatty acid synthesis

GTP-producing TCA step

Succinyl-CoA synthetase yields GTP (substrate-level phosphorylation) in the TCA cycle

ETC Complex I

NADH dehydrogenase; transfers electrons to ubiquinone (Q) and pumps protons

ETC Complex II

Succinate dehydrogenase; transfers FADH₂ to Q; does not pump protons

ETC Complex III

Q cycle; transfers electrons from ubiquinol to cytochrome c and pumps protons

ETC Complex IV

Cytochrome c oxidase; reduces O₂ to H₂O and pumps protons

Oxygen’s role in ETC

O₂ is the final electron acceptor in Complex IV, forming water

Proton motive force and ATP synthesis

Proton gradient drives ATP synthase (Complex V) to convert ADP + Pi to ATP

Glycolysis and fat oxidation integration in fasting

Fatty acid oxidation increases acetyl-CoA and NADH; promotes pyruvate carboxylase activity and inhibits PDH to favor glucose sparing

Amino acids as anaplerotic substrates

Amino acids replenish TCA intermediates, e.g., glutamate → α-KG; alanine → pyruvate

Randle cycle

Fatty acid oxidation inhibits glucose oxidation through cross-talk at acetyl-CoA, citrate, and other intermediates