Govt Exams
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.
In the Warburg effect, PFK-2 and PKM2 are upregulated. PFK-2 produces fructose-2,6-bisphosphate (a potent PFK-1 activator), while PKM2 (pyruvate kinase isoform) is upregulated in cancer cells. PKM2 also has non-glycolytic functions in cancer metabolism.
The PFK reaction is highly exergonic (ΔG°' = -14.2 kJ/mol) and is essentially irreversible. During gluconeogenesis, fructose-1,6-bisphosphatase catalyzes the reverse reaction. This is a major control point in carbohydrate metabolism.
PFK is inhibited by high ATP, citrate (signal of sufficient acetyl-CoA), and low pH. In aerobic conditions, efficient oxidative phosphorylation produces sufficient ATP, reducing need for glycolysis (Pasteur effect). Citrate is an allosteric inhibitor of PFK.
Classic galactosemia results from deficiency of galactose-1-phosphate uridyltransferase (GALT), preventing conversion of galactose-1-phosphate to UDP-galactose. Leads to accumulation of galactose-1-phosphate and galactitol (in polyol pathway), causing cataracts, intellectual disability, and liver damage.
In non-competitive inhibition, the inhibitor binds to an allosteric site on both E and ES, preventing product formation. This decreases Vmax (fewer active enzymes) while Km remains unchanged (substrate binding affinity unaffected).
Proline is an imino acid with its side chain bonded to the backbone nitrogen, eliminating the NH group needed for β-sheet hydrogen bonding between strands. High proline content disrupts β-sheet formation, commonly found in turns and loops instead.
Substituting a nonpolar residue with a charged, hydrophilic one in the protein core disrupts critical hydrophobic interactions that stabilize the tertiary structure, leading to misfolding, aggregation, or degradation.
E3 ubiquitin ligases catalyze the attachment of ubiquitin chains (primarily through Lys48 linkages) to lysine residues on target proteins. The 19S proteasomal subunit recognizes these polyubiquitin chains and unfolds the protein for degradation.