NBME PHYSIOLOGY UPDATED EXAM WITH COMPLETE SOLUTIONS 2023/2024

NBME PHYSIOLOGY UPDATED EXAM WITH COMPLETE SOLUTIONS 2023/2024 Prostglandin - CORRECT ANSWER-From mast cells, macrophages, EC, and platelets Vasodilation, pain Rate controlling step in Insulin secretion - CORRECT ANSWER-Phosphorylation of glucose by glucokinase Glucokinase mutation - CORRECT ANSWER-Autosomal dominant form of early onset type 2 diabetes GLUT 2 - CORRECT ANSWER-low affinity high capacity glucose transporter. Uptake by beta cells Insulin release - CORRECT ANSWER-Blood glucose trips an ATP dependent switch in beta cells ATP sensitive potassium channel closes when ATP/ADP is high. Depolarized membrane triggers Voltage dependent Ca+ channel to open. Calcium pours in, and triggers granule exocytosis of Insulin Glucokinase - CORRECT ANSWER-Glucose to G6P (phosphorylation) Sulfonylurea - CORRECT ANSWER-Anti-Diabetic Drug Repaglinidine (Prnadin) - CORRECT ANSWER-Anti-Diabetic Drug Absorpitive insulin signal transduction - CORRECT ANSWER-Parasympathetic Neuronal - intrapancreatic Ach on M3 receptor - IP3/Ca2+ and PKC on Insulin release . Cori Cycle: - CORRECT ANSWER-Lactate recycle from erythrocytes (or muscle cells) to liver Lactate can be used as substrate for gluconeogenesis Alanine Cycle - CORRECT ANSWER-Alanine Cycle (which was product of pyruvate in muscle) recycle from muscle cells to liver Alanine can be used as substrate for gluconeogenesis Glycolysis - CORRECT ANSWER-Location: RBC, Brain, CNS, Muscle Net: +2ATP, +2 NADH Gluconeogenesis - CORRECT ANSWER-Location: Liver and Kidney Net: -4ATP, -2 GTP, -2 NADH Rate limiting step: Fructose 1,6bisphosphatase -Conversion of Fructose 1,6 bisphosphate to Fructose 6 Phosphate Fructose 1,6 bisphosphatase - CORRECT ANSWER-activated by glucagon inhibited by F2,6 Biphosphotase Malate/Oxcoloacetate - CORRECT ANSWER-Pyruvate converted to OAA then malate Malate transferred outside of cytoplasm and converted to OAA then PEP Prevents Pyrvuate from immediately returning into gluconeogenesis PEP Carboxylase - CORRECT ANSWER-Turns OAA into PEP. (2nd part of pyruvate turning into PEP). First step of glycolysis Inhibited by Insulin Stimulated by Glucagon Glucose 6 phosphatase - CORRECT ANSWER-Located on the luminal side of the ER of liver cells. Starts gluconeogenesis Diabetes Mellitus - CORRECT ANSWER-Lack of insulin (type 1) or insufficient insulin to overcome insulin resistance (type 2) causes gluconeogenesis pathway to be uninhibited even at high blood glucose. type 2 diabetes has 3x rate of gluconeogenesis. Liver pumps out glucose Metformin - CORRECT ANSWER-For type 2 diabetes Stimulates liver AMPK (AMP-activated protein kinase). Causes insulin independent inhibition of gluconeogenesis SGLT-2 blockers - CORRECT ANSWER-Block SGLT in kidney, that would reabsorb glucose in urine PGC-1 - CORRECT ANSWER-Key regulator of gluconeogenesis (glucose synthesis) Works with transcription factors, including hepatic nuclear factor-4α (HNF-4α) and glucocorticoid receptors, to activate the expression of gluconeogenic genes, such as that encoding phosphoenolpyruvate carboxykinase (PEPCK). Glucagon on Liver - CORRECT ANSWER-cAMP - PKA - CREB - PGC-1 - PEPCK gene expression cascade of phosphorylation steps. only receptors for glucagon are in liver Insulin on Liver - CORRECT ANSWER-Counteracts gluceoneogenesis by blocking PEPCK gene and perhaps by inhibiting PGC-1a expression Glucocorticoids on Liver - CORRECT ANSWER-Glucocorticoids enter cells and bind to a glucocorticoid response element (GRE) , which, with PGC-1a, activate the expression of gluconeogenic genes (PEPCK gene expression) Glucose 6 phosphatase is only in - CORRECT ANSWER-The Liver. Only gluceoneogenesis happens in the liver. Precursors of gluconeogenesis - CORRECT ANSWER-Lactate, glycerol, and several amino acids Never acetyl-coA Gluconeogenesis requires - CORRECT ANSWER-ATP, GTP, NADH F2, 6BP stimulates - CORRECT ANSWER-Glycolysis Pyruvate Carboxylase requires a cofactor called - CORRECT ANSWER-Biotin Pyruvate carboxylase - CORRECT ANSWER-is activated by high acetyl coA levels, which happens during fasting. Converts pyruvate to Oxaloacetate and then to malate. Glucagon and Gluconeogenesis - CORRECT ANSWER-Glucagon, via cAMP, promotes phosphorylation of pyruvate kinase rendering it less active. PEP more likely to go backwards towards glucose, than to pyruvate. Glucagon lowers the levels of fructose 2,6 bisphosphate. Fructose 1,6 bisphosphatase is less inhibited. Glycogen levels in liver - CORRECT ANSWER-Highest in evening after dinner. Drop overnight while sleeping Glycogen branch - CORRECT ANSWER-alpha 1,6 glycosidic linkage Branching enzyme - CORRECT ANSWER-Glycogen synthase uses UDP-glucose to activate carbohydrate. Glycogenin (Tyrosine + OH) protein provides a primer for glycogen synthesis. 8 glucose molecules attach (Tyr-O-(Glucose)8) Glycogenin is a self-glucosylating enzyme. Glycogen breakdown - CORRECT ANSWER-Glycogen Phosphorylase (Rate limiting) breaks glycogen into glucose-1-phosphate, which turns into glucose 6-p. Debranching enzyme: Transferase: transfers 3 groups of branch to main branch and a1,6 Glucosidase - cleaves off last glucose on branch G6p fates - CORRECT ANSWER-Pentose phosphate, glycolysis or to gluconeogenesis (glucose 6 phosphatase) Glycogen synthase is activated by - CORRECT ANSWER-Glucose stimulates dephosphorylation of glycogen synthase to form active Glycogen synthase enzyme. It is the rate limiting step Epinepherine - CORRECT ANSWER-Signals breakdown of glycogen in muscle, and somewhat in liver cAMP mediated cascade Beta agonist - CORRECT ANSWER-Glucagon and b-agonists activate adenylyl cyclase, leading to a rise in cAMP. cAMP stimulates glycogenolysis to glucose, leading to increased blood glucose levels. Glucagon does not act on muscle, however b-agonists do. Glycogenolysis is simulated, but since muscle does not synthesize glucose, it converts pyruvate to lactate which is secreted into the bloodstream. Glycogen is less osmotically active - CORRECT ANSWER-Takes away hydration points that monosaccharides have. UDP glucose - CORRECT ANSWER-Provides glucose for synthesis Glycogen storage diseases - CORRECT ANSWER-Deficiency of enzymes for glycogen synthesis 4 kind below 1. (von Gierke's disease) - CORRECT ANSWER-Glucose-6-phosphatase deficiency. Final step of gluconeogenesis and glycogenolyis to produce glucose is defect . Growth failure and lactic acidosis/ hyperuricemia with hepatomegaly; 'doll-like' face; no pathologic muscle symptoms. 2. (Cori's disease). - CORRECT ANSWER-Glycogen debranching enzyme deficiency Defect in glycogenolyis Myopathies. 3. (Anderson disease) - CORRECT ANSWER-Glycogen branching enzyme deficiency. Defect in glycogen synthesis . Failure to thrive; death at about age 5 years. No pathologic muscle symptoms. 4. (McArdle disease). - CORRECT ANSWER-Glycogen phosphorylase deficiency. Defect in glycogenolyis Exercise-induced muscle cramps; rhabdomyolysis (breakdown of damaged skeletal muscle tissue). Polylol Metabolism - CORRECT ANSWER-Chronically elevated glucose levels (diabetics) can lead to cataract formation Sorbitol levels increase in the lens of the eye, and can lead to cataract formation. The situation is worse for galactosemics, since dietary galactose can be converted to galactitol that cannot be metabolized further and will rapidly accumulate. Fructose Metabolism - CORRECT ANSWER-In the liver, when fructose enters glycolysis the phosphofructokinase reaction (rate-limiting step) of normal glycolysis is bypassed Fructokinase phosphorylates, and fructose 1-phosphate aldolase breaks it into G3P and Dihydroacetone phosphate Fructokinase block - CORRECT ANSWER-A block in fructokinase gives rise to essential fructosuria (a very benign disorder) With fructosuria, the increased fructose can be metabolized by hexokinase and used in glycolysis. Hereditary Fructose Intolerance - CORRECT ANSWER-Aldolase B block Fructose 1 phosphate buildu