Govt. Exams
Entrance Exams
Glucose-6-phosphatase catalyzes the dephosphorylation of glucose-6-phosphate to free glucose, which is the final and rate-limiting step of hepatic gluconeogenesis.
Von Gierke disease causes hepatomegaly, lactic acidosis, and hyperuricemia due to glucose-6-phosphatase deficiency, leading to increased glycolysis and purine metabolism.
Classical galactosemia results from galactose-1-phosphate uridylyltransferase (GALT) deficiency, causing accumulation of galactose-1-phosphate which is toxic to liver, brain, and lens. This leads to the classic triad of neonatal jaundice, hepatomegaly, and cataracts. Early dietary restriction of lactose prevents complications.
The Pasteur effect describes how aerobic respiration inhibits glycolysis through multiple mechanisms: increased ATP/AMP ratio (inhibiting PFK-1), increased NADH/NAD⁺ ratio (inhibiting GAPDH), and increased citrate (allosteric inhibitor of PFK-1). This explains why cells prefer oxidative metabolism when oxygen is available.
RBCs lack galactokinase and UDP-galactose-4-epimerase, making them unable to utilize galactose. They can metabolize glucose, fructose (via hexokinase), and mannose. This is relevant to understanding galactosemia pathophysiology where galactose accumulates in RBCs.
Pompe disease (GSD II) involves α-1,4-glucosidase (acid maltase) deficiency, affecting lysosomal glycogen breakdown in muscle tissue. Von Gierke (GSD I) affects liver; Cori (GSD III) affects debranching enzyme; Tarui (GSD VII) affects phosphofructokinase.
In Pompe disease, acid α-glucosidase deficiency prevents lysosomal glycogen hydrolysis. Normally structured glycogen accumulates in lysosomes (unlike the abnormal structures seen in Type IV GSD), causing lysosomal dysfunction and cellular damage.
While this is primarily a hemoglobin question, HbF (with γ-chains instead of β-chains) does not polymerize like HbS or aggregate like HbC, reducing hemolysis and RBC sickling/crystallization.
Muscle phosphorylase deficiency prevents glycogen breakdown, depriving muscles of glucose-1-phosphate during exercise, causing severe energy crisis, fatigue, cramps, and myoglobinuria.
G6Pase is the final enzyme in both gluconeogenesis and glycogenolysis. Its deficiency traps glucose-6-phosphate, forcing it through glycolysis and the pentose phosphate pathway, increasing pyruvate and lactate production.
