Entrance Exams
Govt. Exams
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.
NADPH from the pentose phosphate pathway serves as the primary reducing agent for biosynthetic reactions, especially fatty acid and cholesterol synthesis. It is also crucial for antioxidant defense (glutathione reduction) and biosynthesis of nucleotides.
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.
McArdle disease involves glycogen phosphorylase deficiency in muscle, preventing glycogen breakdown during exercise. This causes exercise intolerance with muscle pain, cramps, fatigue, and myoglobinuria. The 'second wind' phenomenon (improved symptoms after 10 minutes as blood glucose increases) is characteristic.
Hexokinase is inhibited by its product glucose-6-phosphate, making it rate-limiting. Glucokinase, found in liver, is NOT inhibited by G6P, allowing continuous glucose phosphorylation in fed state. This differential regulation is crucial for glucose sensing.
During prolonged fasting, ketone bodies produced from hepatic fatty acid oxidation become the preferred fuel for the brain (up to 60% of energy needs), reducing the requirement for gluconeogenesis and preserving muscle protein.
Sucrose is a non-reducing disaccharide formed by α-1,2-glycosidic linkage between C1 of glucose and C2 of fructose, blocking both anomeric carbons. It cannot mutarotate or act as a reducing sugar. Other options are reducing sugars with free anomeric carbons.
2,3-BPG is synthesized from 1,3-bisphosphoglycerate by bisphosphoglycerate mutase. 2,3-BPG binds to hemoglobin, decreasing its oxygen affinity, facilitating oxygen release to tissues. This shunt allows RBCs to regulate oxygen delivery without producing ATP.