Lipid Metabolism, Amino Acid Biosynthesis, and Cancer Metabolism

Comprehensive flashcards covering lipid synthesis and oxidation, nitrogen fixation, amino acid and nucleotide pathways, and rewired metabolism in cancer cells based on lecture notes.

Metabolic Isotope Tracing

A technique that tracks substrates through metabolic pathways by following heavy stable or radioactive carbon isotopes (such as ${}^{13}\text{C}$ or ${}^{14}\text{C}$) using mass spectrometry.

Triacylglycerol

A neutral lipid formed by attaching three fatty acid chains to a glycerol backbone, which neutralizes reactive fatty acid carboxyl groups for stable, long-term energy storage.

Trans Fatty Acids

Unsaturated fatty acids containing chemically hydrogenated $trans$ double bonds that mimic saturated fatty acids, cannot be metabolized by most organisms, and elevate bad cholesterol (LDL).

Glycerophospholipid

A major membrane lipid component consisting of a glycerol backbone esterified to two fatty acid tails and a phosphate group bound to a head group alcohol.

HMG-CoA Reductase

The rate-limiting enzyme in cholesterol biosynthesis that converts $\beta\text{-hydroxy-}\beta\text{-methylglutaryl-CoA}$ (HMG-CoA) to mevalonate; it is the primary pharmacological target of statin drugs.

Chylomicron

A large, low-density lipoprotein particle synthesized in the intestine that contains apolipoprotein ApoB-48 and carries dietary triglycerides through the lymphatic system and blood to the liver and peripheral tissues.

Apolipoprotein B-100 (ApoB-100)

The primary structural apolipoprotein backbone synthesized in the liver that forms the core organizational structure of VLDL and LDL particles.

Apolipoprotein E (ApoE)

A surface apolipoprotein on chylomicrons, VLDL, and HDL that mediates lipid particle receptor binding; its human $\text{ApoE4}$ allele is a strong genetic predictor of Alzheimer's disease.

Acetyl-CoA Carboxylase (ACC)

A major lipogenic enzyme highly expressed in liver and adipose tissue that uses an ATP-dependent covalent biotin cofactor to carboxylate acetyl-CoA to malonyl-CoA.

Fatty Acid Synthase (FAS)

A multifunctional enzyme complex containing five core domains that sequentially condenses acetyl-CoA and malonyl-CoA units to synthesize the 16-carbon saturated fatty acid palmitate.

Acyl Carrier Protein (ACP) Domain

A domain of fatty acid synthase containing a covalently attached $\text{4'-phosphopantetheine}$ prosthetic group that holds and escorts the growing fatty acyl chain between catalytic active sites.

Perilipin (PLN1)

A lipid droplet coating protein that guards against lipolysis in the basal state; upon phosphorylation, it releases the coactivator CGI-58 to activate adipose triglyceride lipase (ATGL).

Carnitine Palmitoyltransferase 1 (CPT1)

An enzyme located on the outer mitochondrial membrane that catalyzes the transesterification of cytosolic fatty acyl-CoA to acylcarnitine, enabling transport into the mitochondrial matrix for $\beta\text{-oxidation}$.

$$\beta\text{-Oxidation}$$

A four-step mitochondrial pathway (dehydrogenation, hydration, oxidation, thiolysis) that repeatedly cleaves fatty acyl-CoA molecules into two-carbon acetyl-CoA units, generating $\text{NADH}$ and $\text{FADH}_2$.

Stearoyl-CoA Desaturase 1 (SCD1)

An endoplasmic reticulum membrane enzyme that utilizes electrons from $\text{NADPH}$ via cytochrome $b_5$ to introduce a $cis$ double bond at C9-C10 of saturated fatty acyl-CoAs, increasing membrane fluidity.

Nitrogen Fixation

The biological process by which diazotrophic organisms reduce atmospheric dinitrogen gas ($\text{N}_2$) into biologically available ammonia ($\text{NH}_3$ / $\text{NH}_4^+$).

Denitrification

An anaerobic respiratory process in microorganisms that utilizes nitrate ($\text{NO}_3^-$) or nitrite ($\text{NO}_2^-$) as terminal electron acceptors instead of oxygen, reducing them back to dinitrogen gas ($\text{N}_2$).

Anammox

Anaerobic ammonia oxidation carried out by specialized bacteria that converts ammonium ($\text{NH}_4^+$) and nitrite ($\text{NO}_2^-$) directly into dinitrogen gas ($\text{N}_2$).

Nitrate Reductase

An assimilatory enzyme containing a molybdenum cofactor (MoCo) that uses $\text{NADH}$ as an electron donor to reduce nitrate ($\text{NO}_3^-$) to nitrite ($\text{NO}_2^-$).

Nitrite Reductase

An oxygen-sensitive assimilatory enzyme containing an iron-sulfur cluster and siroheme cofactor that uses reduced ferredoxin to transfer 6 electrons, reducing nitrite ($\text{NO}_2^-$) to ammonium ($\text{NH}_4^+$).

Nitrogenase Complex

A two-component enzyme system consisting of dinitrogenase reductase (Fe protein) and dinitrogenase (MoFe protein) that requires $16\,\text{ATP}$ per $\text{N}_2$ to break the $\text{N}\equiv\text{N}$ triple bond.

Glutamine Synthetase

The central regulatory enzyme for cellular ammonia assimilation that catalyzes the ATP-dependent addition of ammonium ($\text{NH}_4^+$) to glutamate to form glutamine; it is post-translationally inactivated by adenylylation on an active site tyrosine.

$$\Delta^1\text{-Pyrroline-5-Carboxylate (P5C)}$$

A cyclic intermediate in proline biosynthesis formed by the spontaneous, non-enzymatic cyclization of glutamate-5-semialdehyde.

DAP Pathway (Diaminopimelate Pathway)

A bacterial and plant biosynthetic pathway stemming from aspartate—absent in humans—that generates $\text{meso-diaminopimelate}$ for peptidoglycan cell wall cross-linking and produces essential lysine.

Glutathione (GSH)

An abundant tripeptide ($\gamma\text{-Glu-Cys-Gly}$) synthesized by $\gamma\text{-glutamylcysteine synthetase}$ and glutathione synthetase that protects cells against oxidative stress by maintaining cellular redox state.

Ribonucleotide Reductase

An enzyme containing active site dithiol groups and an iron-dependent $\beta$ subunit that converts ribonucleoside diphosphates (NDPs) to deoxyribonucleoside diphosphates (dNDPs) using thioredoxin as a reductant.

Warburg Effect (Aerobic Glycolysis)

The metabolic phenotype of cancer cells characterized by markedly elevated rates of glucose uptake and glycolysis with lactate secretion, even in the presence of abundant oxygen.

$${}^{18}\text{F}\text{-FDG PET Imaging}$$

A diagnostic imaging technique that detects high tumor glycolytic rates by tracking the uptake and intracellular trapping of the phosphorylated radiolabeled glucose analog ${}^{18}\text{F}\text{-2-deoxyglucose}$.

PI3K/Akt/mTOR Pathway

An oncogenic signaling cascade frequently activated by mutations (such as in $\text{PIK3CA}$, $\text{Akt2}$, or loss of $\text{PTEN}$) that drives cell-autonomous glucose transport, glycolytic rate, lipid synthesis, and protein translation.

TIGAR

TP53-Induced Glycolysis and Apoptosis Regulator; an enzyme induced by p53 that decreases fructose-2,6-bisphosphate levels, inhibiting glycolysis and diverting glucose-6-phosphate into the Pentose Phosphate Pathway to lower reactive oxygen species (ROS).

Glutamine Anaplerosis

The metabolic process by which proliferating cancer cells consume high levels of glutamine and convert it via glutaminase (GLS) to $\alpha\text{-ketoglutarate}$ to replenish TCA cycle intermediates and support ATP production.

AMPK Pathway

A metabolic stress-sensing pathway activated by an increased AMP:ATP ratio that activates p53, inhibits lipid and protein synthesis, induces cell cycle arrest via p21, and promotes autophagy and $\beta\text{-oxidation}$.

Autophagy

A lysosomal degradation process by which cells break down cytoplasmic organelles and proteins in autophagolysosomes to recycle nutrients and maintain energy homeostasis during nutrient starvation or metabolic stress.

2-Hydroxyglutarate (2HG)

An oncometabolite produced by neomorphic mutant IDH1 (R132) or IDH2 (R172/R140) enzymes that competitively inhibits $\alpha\text{-ketoglutarate-dependent}$ dioxygenases, causing epigenetic rewiring and blocking cell differentiation.

Ivosidenib (TIBSOVO)

An FDA-approved targeted oral inhibitor specific for mutant IDH1 used in adult patients with relapsed or refractory acute myeloid leukemia (AML).