Govt Exams
NADP+ is reduced to NADPH in the oxidative phase of the pentose phosphate pathway, primarily in the G6PD and 6-PGD reactions.
Pompe disease results from deficiency of acid α-glucosidase (lysosomal α-1,4-glucosidase), leading to accumulation of glycogen in lysosomes, especially in muscles and heart.
Under anaerobic conditions, pyruvate is reduced to lactate by lactate dehydrogenase (LDH) to regenerate NAD+ for continued glycolysis.
During exercise, epinephrine increases and ATP/AMP ratio decreases, both of which activate phosphorylase kinase and promote glycogenolysis.
Acetyl-CoA condenses with oxaloacetate to form citrate, which enters the citric acid cycle. Citrate synthase catalyzes this reaction.
Glycogen's highly branched structure with α-1,6-branch points every 8-12 glucose residues increases its solubility, provides multiple substrate sites for glycogen phosphorylase simultaneously, and enables rapid glucose mobilization during energy demands. This is metabolically superior to linear polymers.
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.
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.