Hexose Monophosphate Pathway and G6PD Deficiency

Vocabulary practice cards covering the reactions, regulation, enzymes, and clinical conditions associated with the hexose monophosphate pathway, respiratory burst, and G6PD deficiency.

Hexose Monophosphate (HMP) Pathway

A cytosolic metabolic pathway active in the liver, lactating mammary glands, adrenal cortex, and red blood cells that generates NADPH and ribose 5-phosphate from glucose 6-phosphate without consuming or producing ATP.

Glucose 6-Phosphate Dehydrogenase (G6PD)

The rate-limiting regulatory enzyme of the pentose phosphate pathway that catalyzes the oxidation of glucose 6-phosphate to 6-phosphogluconolactone, allosterically activated by $NADP^+$ and inhibited by NADPH.

Oxidative Phase of the HMP Pathway

The irreversible phase of the pathway catalyzed by G6PD and 6-phosphogluconate dehydrogenase that produces two moles of NADPH + $H^+$ and one mole of ribulose 5-phosphate along with $CO_2$ per molecule of glucose 6-phosphate.

Nonoxidative Phase of the HMP Pathway

The reversible series of sugar interconversions beginning with ribulose 5-phosphate that produces ribose 5-phosphate for nucleotide synthesis and recycles excess pentoses back into glycolytic intermediates (fructose 6-phosphate and glyceraldehyde 3-phosphate).

Transketolase

A thiamine pyrophosphate (TPP, vitamin $B_1$)-dependent enzyme of the nonoxidative branch; it is the sole thiamine-dependent enzyme in erythrocytes and its activity is measured to clinically diagnose nutritional thiamine deficiency (beriberi).

Malic Enzyme

An enzyme in hepatic tissue that provides an alternative intracellular source of NADPH separate from the hexose monophosphate shunt.

Free Radicals

Highly reactive, unstable chemical species containing an unpaired electron in their outer orbital shell that cause cellular pathology by inducing DNA strand breakage, modifying proteins, and driving lipid peroxidation of membranes.

Superoxide Dismutase (SOD)

The antioxidant enzyme responsible for converting superoxide anions ($O_2^{\bullet-}$) generated by NADPH oxidase into hydrogen peroxide ($H_2O_2$) within the phagolysosome.

Myeloperoxidase (MPO)

A lysosomal enzyme found in phagocytes that utilizes hydrogen peroxide ($H_2O_2$) and chloride ions ($Cl^-$) to synthesize bactericidal hypochlorous acid ($HOCl^\bullet$).

Chronic Granulomatous Disease (CGD)

A primary immunodeficiency caused by loss-of-function mutations in NADPH oxidase that impairs the phagocytic respiratory burst, leaving phagocytes unable to kill catalase-positive microbes and leading to recurrent granuloma formation.

Catalase-Positive CGD Pathogens

A group of five organisms that cause nearly all infections in CGD by enzymatically destroying their own endogenous $H_2O_2$, preventing host phagocytes from utilizing it: Staph aureus, Pseudomonas, Serratia, Nocardia, and Aspergillus.

Myeloperoxidase Deficiency

An autosomal recessive condition caused by mutations in the MPO gene characterized by impaired hypochlorous acid production despite an intact respiratory burst, predisposing patients to recurrent Candida infections or presenting asymptomatically.

Glutathione Peroxidase

A selenium-dependent enzyme that serves as the major antioxidant mechanism in erythrocytes by reducing hydrogen peroxide ($H_2O_2$) to water ($H_2O$) via oxidation of reduced glutathione (GSH) to oxidized glutathione (GSSG).

Glutathione Reductase

A riboflavin-dependent enzyme that recycles oxidized glutathione (GSSG) back into its protective reduced state (GSH) using reducing equivalents donated by NADPH.

Glucose 6-Phosphate Dehydrogenase Deficiency

The most common human enzymatic defect worldwide (affecting approximately 400 million individuals), characterized by X-linked recessive inheritance and susceptibility to episodic acute hemolytic anemia triggered by oxidative stress.

Heinz Bodies

Intracellular precipitates of denatured globin and oxidized hemoglobin within red blood cells, visible on supravital staining following oxidative stress.

Bite Cells

Abnormally contoured red blood cells produced when splenic macrophages pluck out rigid Heinz body inclusions as erythrocytes pass through the spleen.

Favism

A clinical syndrome of severe hemolytic anemia, pallor, jaundice, and hemoglobinuria developing 24 to 48 hours after ingestion of broad beans (fava beans) in susceptible individuals with G6PD deficiency.

Fluorescent Spot Test

A screening diagnostic assay for G6PD deficiency that measures the generation of NADPH from $NADP^+$; blood samples that fail to fluoresce under ultraviolet light confirm enzymatic deficiency.

Scleral Icterus

Yellowing of the sclera caused by elevated serum unconjugated bilirubin levels resulting from acute intravascular hemolysis in G6PD deficiency.

Hemoglobinuria

The excretion of free hemoglobin into the urine causing it to turn reddish-brown and test positive on a urine dipstick for blood in the absence of intact erythrocytes.