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[collegeandknowledge]

Old GRE questions I had saved. Deleting things from my One Drive

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[collegeandknowledge]

Cold process soap. Made from scratch.

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Glucolipotoxicity

Caused by excess of glucose and fatty acid. Is characterized by beta cell hypersecretion of insulin, impairment of normal glucose-sensitive insulin secretion (GSIS). The glucose dose response curve will show a leftward shift. Can be fixed by decreasing lipid stores.

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hydrophilic statin less likely to result in diabetes than lipophilic statin. Lipophilic statins cross the bilayer more easily and have a stronger effect than hydrophilic statins. Coq10 comes into play with hydro- and lipophilic statins. Statins inhibit production of mevalonate by HMG CoA reductase. If you’re not getting as much statin into the cell, you’re not reducing coq10′s ability to deliver protons to produce ATP. Lower ATP means not as high a chance of diabetogenic effect (Excess ATP goes to glycogen storage, characteristic of fatty liver in T2DM).

Overall, lower incidence of diabetes with hydrophilic statins than with lipophilic statins. Hydrophilic statins are better.

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Fatty acids bind to the GPR40 receptor. Once bound, Phospholipase C is triggered to give you IP3 and DAG. (PLC activates PIP2. PIP2 gives you IP3). IP3 stimulates a receptor at the ER to release calcium. DAG binds to MUNC13 and causes exocytosis. DAG and calcium activate Protein Kinase C, an effector of insulin exocytosis.

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“The effects of sodium intake on CVD events is largely unrelated to the effects of sodium intake on BP.” Mente et al., 2018

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Long chain CoA is the form of fatty acid that gets transported into the mitochondria.

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As long as acetyl CoA production is sustained, excess fuel produces ROS and drives the NNT to maintain an equilibrium and keep everything in balance (NNT converts NADH to NADPH; NADPH keeps glutathione in its reduced state to deal with ROS).

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SEAHORSE: kinetic measurements of oxygen consumption

You have cells in a plate and a microchamber that makes the volume low enough that it can sensitively detect changes in oxygen partial pressure. There is a cartridge that sits on top of the plate; the cartridge has probes that measure oxygen partial pressure and pH. There’s also injection ports that allow for the injection of compounds (e.g. complex inhibitors like rotenone, antimycin A, cyanide, etc.) During measurement, the cartridge comes down and blocks the cells off from the rest of the well, forming a 2-3 micrometer microchamber. You’ll start with an oxygen partial pressure and pH that’s under normal conditions. After 3-4 minutes, you see a decrease in oxygen partial pressure and pH in the well. You can lift the cartridge, mix components in the well to bring things back to normal levels, and then use the O2 partial pressure slope and pH change to determine the O2 consumption rate and extracellular acidification rate that’s associated with lipolysis.

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I often forget what’s inhibiting what complex. The inhibitors we discuss only block complex 1, complex III, complex IV, and the ATPase. For this exam, Dr. Stiles wants us to know: rotenone, antimycin A, cyanide, and oligomycin.

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Flux = tracer infusion rate/tracer enrichment

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A diabetic doesn’t inhibit PEPCK, so glucose will continue to be produced.

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Under high energy balance, your acetyl-CoA is being carboxylated to malonyl CoA, and this inhibits fatty acid transportation into the mitochondria. Under low energy balance, the opposite effect is happening (more fatty acid is oxidized in the mitochondria to produce ATP). Insulin is a key regulator of this mechanism.

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Glycogen Breakdown

Phosphorylase b is activated to phosphorylase by the enzyme phosphorylase b kinase. Phosphorylase b kinase is activated by protein kinase A or high calcium level. Once phosphorylase b kinase is activated by protein kinase a, it activates phosphorylase b to its active form called phosphorylase a. Phosphorylase a breaks glycogen to glucose-1-phosphate. Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate.

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To make glycogen: glucose-6-phosphate is converted to glucose-1-phosphate via phosphoglucomutase, glucose-1-phosphate is converted to UDP-glucose via UDP-glucose pyrophosphorylase and UTP, and lastly glycogen synthase converts UDP-glucose to glycogen.

To break down glycogen for glucose: glycogen is broken to glucose-1-phosphate using phosphorylase, glucose-1-phosphate is converted to glucose-6-phosphate using phosphoglucomutase, then in the liver glucose-6-phosphate is converted to glucose using glucose-6-phosphatase.