Biochemistry: Lipid and Amino Acid Metabolism

Comprehensive vocabulary flashcards covering fatty acid mobilization, transport, beta-oxidation, ketogenesis, fatty acid synthesis, glyceroneogenesis, and amino acid catabolism/biosynthesis.

Triacylglycerols

Nonpolar lipid esters composed of three fatty acids linked to a glycerol backbone that serve as long-term fuel storage, supplying about one-third of dietary energy needs and storing more energy per carbon than carbohydrates because they are more chemically reduced and unhydrated.

Chylomicrons

Plasma lipoprotein aggregates ($100$ to $500\,\text{nm}$ in diameter) that package and transport dietary lipids from the vertebrate small intestine through the bloodstream; they feature a surface monolayer of phospholipids and apolipoproteins (such as B-48, C-II, and C-III) enclosing a core containing over $80\%$ triacylglycerols and cholesteryl esters.

Hormone-Sensitive Lipase (HSL)

An adipocyte enzyme that is phosphorylated and activated by protein kinase A (PKA) in response to glucagon or epinephrine; it binds to phosphorylated perilipin on the lipid droplet surface to hydrolyze diacylglycerols into monoacylglycerols.

Perilipin

A family of proteins coating the surface of intracellular lipid droplets that restricts lipolytic enzyme access; phosphorylation by PKA causes the release of the activator protein CGI and allows active hormone-sensitive lipase access to droplet lipids.

Adipose Triacylglycerol Lipase (ATGL)

An adipocyte lipase that binds to the regulatory protein CGI (after its dissociation from phosphorylated perilipin) to catalyze the initial cleavage of stored triacylglycerols into diacylglycerols.

Acyl-Carnitine/Carnitine Transporter

An inner mitochondrial membrane antiporter that shuttles fatty acyl-carnitine into the mitochondrial matrix by facilitated diffusion while returning free carnitine to the intermembrane space for fatty acids containing $12$ or more carbons.

$\beta$-Oxidation

A recurring four-step mitochondrial pathway that cleaves long-chain fatty acids into two-carbon acetyl-CoA units, generating one molecule of $\text{FADH}_2$ and one molecule of $\text{NADH}$ during each round of oxidation.

Trifunctional Protein (TFP)

An inner mitochondrial membrane-associated hetero-octamer ($\alpha_4\beta_4$) that processes fatty acid chains of $12$ or more carbons; its $\alpha$ subunits harbor enoyl-CoA hydratase and $\beta$-hydroxyacyl-CoA dehydrogenase activities, while its $\beta$ subunits harbor long-chain thiolase activity.

Enoyl-CoA Isomerase

An auxiliary enzyme required during the oxidation of unsaturated fatty acids that converts naturally occurring $cis$ double bonds starting at carbon $3$ into $trans$ double bonds recognizable by enoyl-CoA hydratase.

Propionyl-CoA

A three-carbon thioester product formed during the final cleavage step in the $\beta$-oxidation of odd-numbered fatty acids; it is subsequently carboxylated and isomerized to yield succinyl-CoA.

Methylmalonyl-CoA Mutase

A mitochondrial enzyme requiring coenzyme $\text{B}_{12}$ that catalyzes an intramolecular rearrangement exchanging a hydrogen atom and a carbonyl-CoA group on adjacent carbons to convert L-methylmalonyl-CoA to succinyl-CoA.

Ketone Bodies

Water-soluble fuel molecules—specifically acetoacetate, D-$\beta$-hydroxybutyrate, and acetone—synthesized in liver mitochondria from excess acetyl-CoA when oxaloacetate is depleted and exported to extrahepatic tissues like the heart, skeletal muscle, kidney, and brain.

HMG-CoA Lyase

A mitochondrial matrix enzyme that cleaves $\beta$-hydroxy-$\beta$-methylglutaryl-CoA (HMG-CoA) into free acetoacetate and acetyl-CoA during the pathway of ketone body synthesis.

Acetyl-CoA Carboxylase (ACC)

The rate-limiting, biotin-dependent enzyme that catalyzes the carboxylation of acetyl-CoA using $\text{HCO}_3^-$ and ATP to form malonyl-CoA; it is allosterically activated by citrate, inhibited by palmitoyl-CoA, and inactivated by PKA phosphorylation.

Malonyl-CoA

The three-carbon activated donor of two-carbon units during fatty acid synthesis that also serves as an allosteric inhibitor of carnitine acyltransferase I, preventing simultaneous synthesis and mitochondrial degradation of fatty acids.

Fatty Acid Synthase (FAS)

A multifunctional enzyme complex (FAS I in vertebrates and fungi; FAS II in plants and bacteria) that iteratively lengthens a growing fatty acyl chain by two carbons per cycle using malonyl-CoA and NADPH through condensation, reduction, dehydration, and reduction steps.

Citrate Lyase

A cytosolic enzyme that cleaves mitochondrial-derived citrate in an ATP-dependent reaction with coenzyme A to regenerate cytosolic acetyl-CoA and oxaloacetate for fatty acid biosynthesis.

Malic Enzyme

A cytosolic enzyme that catalyzes the oxidative decarboxylation of malate into pyruvate and $\text{CO}_2$, reducing $\text{NADP}^+$ to NADPH to provide reducing power for lipid biosynthesis.

Cyclooxygenase (COX)

A bifunctional heme enzyme (prostaglandin $\text{H}_2$ synthase) containing both cyclooxygenase and peroxidase activities that converts arachidonate ($20:4(\Delta^{5,8,11,14})$) into prostaglandin $\text{PGH}_2$, the common precursor of prostaglandins and thromboxanes.

Phosphatidic Acid

A central glycerolipid intermediate composed of a glycerol 3-phosphate backbone esterified with two fatty acyl groups; it acts as the common precursor for the synthesis of both triacylglycerols and glycerophospholipids.

Phosphatidic Acid Phosphatase (Lipin)

An enzyme that removes the phosphate group from the C-3 position of phosphatidic acid to produce 1,2-diacylglycerol, which is subsequently acylated by an acyltransferase to yield a triacylglycerol.

Glyceroneogenesis

An abbreviated gluconeogenic pathway in adipose tissue and liver that converts pyruvate to dihydroxyacetone phosphate (DHAP) via pyruvate carboxylase and PEPCK, supplying glycerol 3-phosphate for fatty acid re-esterification.

Thiazolidinediones

A class of pharmaceutical agents used to treat type 2 diabetes that activate the nuclear receptor $\text{PPAR}\gamma$, inducing adipose PEPCK expression to increase glyceroneogenesis, promote triacylglycerol resynthesis, and lower circulating free fatty acids.

Pyridoxal Phosphate (PLP)

The active coenzyme form of vitamin $\text{B}_6$ that forms a reversible internal aldimine (Schiff base) with a lysine residue of aminotransferases and serves as an intermediate carrier of amino groups during transamination and rearrangement reactions.

Tetrahydrofolate ($\text{H}_4\text{ folate}$)

A versatile coenzyme synthesized from the vitamin folate that acts as an intermediate carrier in the transfer of one-carbon units at various oxidation states during amino acid and nucleotide metabolism.

S-Adenosylmethionine (adoMet)

A sulfonium compound synthesized from ATP and methionine that serves as the primary activated methyl donor in numerous cellular transmethylation reactions.

Alanine Aminotransferase (ALT)

A PLP-dependent enzyme that catalyzes the reversible transfer of an amino group from alanine to $\alpha$-ketoglutarate, producing pyruvate and glutamate as part of the glucose-alanine cycle connecting skeletal muscle to the liver.

Glutamine Synthetase

A cytosolic enzyme that utilizes ATP to combine free toxic ammonium ($\text{NH}_4^+$) with glutamate to produce glutamine, facilitating non-toxic interorgan transport of nitrogen through the bloodstream.

Glutaminase

A mitochondrial enzyme expressed predominantly in the liver and kidneys that hydrolyzes circulating glutamine into glutamate and free ammonium ($\text{NH}_4^+$), channeling the released nitrogen directly into the urea cycle.

Carbamoyl Phosphate Synthetase I (CPS I)

The rate-limiting mitochondrial enzyme of the urea cycle that couples ammonium ($\text{NH}_4^+$) and bicarbonate ($\text{HCO}_3^-$) at the expense of two ATP molecules to form carbamoyl phosphate; it requires N-acetylglutamate as an obligate allosteric activator.

N-Acetylglutamate

An allosteric regulator formed by N-acetylglutamate synthase from acetyl-CoA and glutamate in the presence of arginine that binds to and activates carbamoyl phosphate synthetase I to upregulate urea synthesis.

Ketogenic Amino Acids

Amino acids whose carbon skeletons are degraded directly into acetoacetyl-CoA or acetyl-CoA (such as leucine and lysine), enabling them to be converted into ketone bodies or fatty acids but not net glucose.

Glucogenic Amino Acids

Amino acids whose carbon skeletons are degraded to pyruvate, $\alpha$-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate, permitting their carbon skeletons to be funneled into gluconeogenesis for net glucose synthesis.

Phenylketonuria (PKU)

An autosomal recessive metabolic disorder caused by a defect in the initial step of phenylalanine degradation, leading to toxic systemic accumulation of phenylalanine and abnormal transamination products such as phenylpyruvate, phenylacetate, and phenyllactate.

Glutathione (GSH)

A tripeptide reducing agent and antioxidant ($\gamma$-glutamylcysteinylglycine) present at high levels in cells that maintains protein thiol groups in reduced form, removes organic peroxides, and dimerizes to oxidized glutathione (GSSG) upon oxidation.