Biochemistry: Lipids, Carbohydrates, TCA Cycle, and Cellular Metabolism

Vocabulary flashcards covering lipid-lowering pharmacological agents, glycolysis pathways and regulation, the citric acid cycle, protein moonlighting, and the mechanism of pancreatic beta-cell insulin secretion.

Bempedoic acid (Nexletol)

A lipid-lowering medication that blocks ATP-citrate lyase (ACL) in the liver during early cholesterol synthesis, resulting in decreased acetyl-CoA production from citrate and decreased cholesterol synthesis.

Statins

Medications (such as atorvastatin) that inhibit HMG-CoA reductase in the liver to decrease cholesterol synthesis, thereby increasing LDL receptors and decreasing blood LDL.

Ezetimibe (Zetia)

A medication that blocks NPC1L1 in the small intestine, decreasing cholesterol absorption from food and bile.

PCSK9 inhibitors

Monoclonal antibodies (such as evolocumab/Repatha and alirocumab/Praluent) that block PCSK9 protein to prevent LDL-receptor destruction mainly in the liver, leading to increased LDL removal from the blood.

Inclisiran (Leqvio)

A therapeutic agent that targets PCSK9 mRNA in liver cells to decrease PCSK9 production, allowing LDL receptors to survive and increasing blood LDL removal.

Substrate-level phosphorylation

A metabolic process in which a phosphate group is transferred directly from a high-energy intermediate to ADP to form ATP.

Phosphofructokinase (PFK)

The major regulatory enzyme of glycolysis that converts fructose-6-P to fructose-1,6-bisphosphate; its activity increases at low $[\text{ATP}]$ and decreases at high $[\text{ATP}]$.

Enolase

A glycolytic enzyme that produces phosphoenolpyruvate (PEP) from 2-phosphoglycerate (2-PG) through a dehydration reaction.

Pyruvate kinase

A glycolytic enzyme that converts phosphoenolpyruvate (PEP) into pyruvate while producing ATP via substrate-level phosphorylation.

Anaplerosis

The replenishment of TCA cycle intermediates using alternative biomolecules, such as pyruvate forming oxaloacetate or glutamate forming $\alpha\text{-ketoglutarate}$.

Fluoroacetate

A toxic compound that is metabolized into fluorocitrate, which inhibits aconitase, leading to citrate accumulation, disruption of the TCA cycle, and reduced ATP production.

Aconitase

A TCA cycle enzyme that rearranges citrate into isocitrate by moving the hydroxyl group from a tertiary to a secondary carbon to prepare it for oxidation.

Isocitrate dehydrogenase

An enzyme in the TCA cycle that oxidizes and decarboxylates isocitrate to form $\alpha\text{-ketoglutarate}$, $\text{CO}_2$, and NADH; it is stimulated by ADP accumulation and slowed by ATP accumulation.

Galactosemia

A metabolic disorder caused by a mutation in Galactose 1-P: Uridyl transferase, leading to toxic accumulations that result in cataracts and permanent neurological disorders.

Warburg Effect

The observed increase in the rate of glycolysis in cancer cells, utilized clinically for tumor detection via PET imaging.

PDH kinase

An enzyme favored by high levels of ATP and NADH that phosphorylates and inactivates pyruvate dehydrogenase (PDH).

PDH phosphatase

An enzyme stimulated by $\text{Ca}^{2+}$ that dephosphorylates and activates pyruvate dehydrogenase (PDH).

Moonlighting protein

A single protein that performs more than one distinct biological function beyond its conventional primary role.

Pyruvate kinase M2 (PKM2)

A moonlighting enzyme that catalyzes glycolysis in the cytosol and can translocate to the nucleus to regulate gene expression and participate in protein phosphorylation.

Kir6.2

The pore-forming subunit of the ATP-sensitive $\text{K}^+$ channel ($\text{K}_{\text{ATP}}$) in pancreatic beta-cells.

SUR1

The regulatory subunit of the ATP-sensitive $\text{K}^+$ channel ($\text{K}_{\text{ATP}}$) in pancreatic beta-cells.

SNARE proteins

Cellular proteins that facilitate the fusion of insulin-containing granules with the plasma membrane to execute exocytosis in pancreatic beta-cells.

$\text{K}_{\text{ATP}}$ channels

Potassium channels in pancreatic beta-cells that close when intracellular ATP rises, causing membrane depolarization, $\text{Ca}^{2+}$ influx, and insulin secretion.