Anaerobic Metabolism - Regulation of Glycolysis and TCA

Vocabulary practice flashcards covering anaerobic metabolism, energy coupling, redox carriers, regulation of glycolysis and the TCA cycle, entry of alternative sugars, and clinical/dental metabolic disorders.

Free Energy Coupling

The pairing of an endergonic, thermodynamically unfavourable reaction (such as glucose phosphorylation with $\Delta G^{\circ\prime} = 13.8\,kJ\,mol^{-1}$) with an exergonic, favourable reaction (such as ATP hydrolysis with $\Delta G^{\circ\prime} = -30.5\,kJ\,mol^{-1}$) to yield an overall exergonic process ($\Delta G^{\circ\prime} = -16.7\,kJ\,mol^{-1}$).

Nicotinamide Adenine Dinucleotide ($NAD^+$)

A major cellular electron carrier that stores energy by accepting two electrons and two protons ($NAD^+ + 2H^+ + 2e^- \rightarrow NADH + H^+$), temporarily conserving energy until it is converted to ATP.

Alcoholic Fermentation

An anaerobic pathway in yeast that regenerates $NAD^+$ by first converting pyruvate to acetaldehyde using pyruvate decarboxylase (releasing $CO_2$), followed by reduction to ethanol by alcohol dehydrogenase.

Lactic Acid Fermentation

An anaerobic adaptation occurring in oxygen-deprived skeletal muscle where pyruvate is reduced to lactate to regenerate $NAD^+$ needed to maintain glycolysis, which also lowers cellular pH.

Allosteric Regulation

A rapid, reversible control mechanism in which effector molecules bind to an enzyme at a distinct allosteric site rather than the active site, inducing a conformational change that increases or decreases enzymatic activity.

Phosphofructokinase-1 (PFK-1) Kinetic Regulation by ATP

The inhibition of PFK-1 by high concentrations of ATP binding to its allosteric site, which shifts the substrate saturation curve for fructose 6-phosphate to a sigmoidal shape and lowers enzyme affinity, whereas low ATP or elevated ADP/AMP restores high activity.

Covalent Modification

A regulatory mechanism involving the enzymatic addition or removal of a chemical group (commonly a phosphate group, $PO_4^{3-}$, added by kinases and removed by phosphatases) to activate or inactivate an enzyme under hormonal or signalling control.

Metabolic Compartmentalisation

The spatial and temporal control of metabolic processes by sequestering enzymes and pathways in distinct cellular compartments, such as confining fatty acid oxidation to mitochondria and fatty acid synthesis to the cytoplasm.

Hexokinase

The initial glycolytic enzyme that phosphorylates glucose to glucose-6-phosphate (G-6P); isozymes I, II, and III are allosterically inhibited by the accumulation of their product, G-6P.

Phosphofructokinase-1 (PFK-1)

The key regulatory enzyme of glycolysis that catalyses the metabolically irreversible phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate with a large negative $\Delta G$, committing the carbon skeleton to glycolysis.

Pyruvate Kinase

The terminal glycolytic enzyme converting phosphoenolpyruvate (PEP) to pyruvate and ATP; it is activated by fructose 1,6-bisphosphate, allosterically inhibited by ATP and alanine, and inactivated by phosphorylation in the liver.

Pyruvate Dehydrogenase (PDH) Complex

A multienzyme complex comprising $E_1$ ($\alpha_2\beta_2$), $E_2$ ($\alpha_3$ transacetylase), and $E_3$ ($\alpha\beta$ dehydrolipoyl dehydrogenase) that links glycolysis to the TCA cycle by catalysing the decarboxylation, oxidation, and transfer of pyruvate to coenzyme A to form acetyl-CoA.

PDH Allosteric Control

The direct inhibition of the pyruvate dehydrogenase complex components by accumulated downstream products, where acetyl-CoA inhibits the $E_2$ transacetylase subunit and NADH inhibits the $E_3$ dehydrolipoyl dehydrogenase subunit.

Citrate Synthase

The enzyme catalysing Step 1 of the TCA cycle (condensation of oxaloacetate and acetyl-CoA into citrate), which is allosterically inhibited by ATP, NADH, citrate, and succinyl-CoA.

Isocitrate Dehydrogenase

The primary rate-limiting enzyme of the TCA cycle (Step 3) that oxidatively decarboxylates isocitrate to $\alpha$-ketoglutarate, $CO_2$, and NADH; it is activated by ADP and $Ca^{2+}$ and inhibited by ATP and NADH.

$\alpha$-Ketoglutarate Dehydrogenase

The TCA cycle enzyme catalysing Step 4 ($\alpha$-ketoglutarate to succinyl-CoA, $CO_2$, and NADH); it is activated by $Ca^{2+}$ during muscle contraction and feedback-inhibited by succinyl-CoA, NADH, and ATP.

Monosaccharide Entry Points in Glycolysis

The entry pathways of non-glucose dietary sugars into glycolysis, where galactose enters as glucose-6-phosphate, fructose from adipose enters as fructose-6-phosphate, and fructose from the liver enters as DHAP and GAP.

Lactase

A brush border enzyme that catalyses the hydrolytic cleavage of the disaccharide lactose into galactose and glucose.

Lactose Intolerance

A condition resulting from a deficiency of lactase, leading to bacterial fermentation of unabsorbed lactose in the colon and causing flatulence, diarrhoea, abdominal bloating, cramps, and nausea.

Galactosaemia

An inherited autosomal recessive metabolic disorder caused by a deficiency in galactose 1-phosphate uridyl transferase, which can result in liver enlargement and central nervous system failure.

Galactitol Formation

The reduction of accumulated galactose to galactitol catalysed by aldose reductase consuming $NADPH + H^+$, leading to cataract formation in patients with galactosaemia.

Fluoride Inhibition of Enolase

An anticaries mechanism whereby fluoride ($F^-$) forms complexes with magnesium and inorganic phosphate (such as $MgF_3^-$) in the bacterial cytoplasm, binding tightly to enolase and blocking the conversion of 2-phosphoglycerate to phosphoenolpyruvate.