Intermediary Metabolism: Fatty Acids, Amino Acids, Urea Cycle, Glycogen, and the Pentose Phosphate Pathway

Comprehensive vocabulary flashcards reviewing lipid metabolism, amino acid catabolism, the urea cycle, glycogen synthesis/breakdown, and the pentose phosphate pathway based on lecture notes.

Acyl-CoA Synthetase

An enzyme that activates free fatty acids into fatty acyl-CoA molecules in the cytoplasm via the reaction $\text{Fatty acid} + \text{CoA} + \text{ATP} \rightarrow \text{acyl-CoA} + \text{AMP} + \text{PP}_\text{i}$, which is driven forward by pyrophosphatase hydrolyzing $\text{PP}_\text{i}$ to $2\,\text{P}_\text{i}$.

Carnitine Shuttle

The multi-component transport mechanism responsible for shuttling activated fatty acyl chains across the inner mitochondrial membrane into the matrix, utilizing carnitine palmitoyltransferase I (CPT-I), carnitine-acylcarnitine translocase, and carnitine palmitoyltransferase II (CPT-II).

Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency

One of the most common inborn errors of metabolism, characterized by vomiting, lethargy, coma, and severe hypoglycemia following a $12\,\text{hr}$ fast; hypoglycemia occurs because impaired fatty acid oxidation forces tissues to consume glucose while concurrently suppressing gluconeogenesis.

Ketogenesis

The metabolic pathway occurring primarily within liver mitochondria that converts excess acetyl-CoA into water-soluble ketone bodies (acetoacetate, D-3-hydroxybutyrate, and the non-metabolized byproduct acetone) to serve as alternative cellular fuel during prolonged fasting.

Acetyl-CoA Carboxylase (ACC)

The rate-limiting biotin-dependent enzyme of fatty acid synthesis that carboxylates acetyl-CoA to malonyl-CoA using $\text{ATP}$ and $\text{HCO}_3^-$; it is allosterically activated by citrate and inhibited by long-chain acyl-CoA as well as phosphorylation by PKA and AMPK.

Fatty Acid Synthase (FAS)

A multifunctional homodimeric enzyme complex ($272\,\text{kDa}$ per subunit) with seven catalytic domains and an acyl carrier protein (ACP) domain that sequentially adds two-carbon units from malonyl-ACP to produce palmitic acid.

Citrate-Pyruvate Shuttle

An intracellular pathway that transfers mitochondrial acetyl-CoA into the cytoplasm as citrate via ATP-citrate lyase, concurrently generating cytoplasmic $\text{NADPH}$ ($8\,\text{NADPH}$ per $8\,\text{cycles}$) through malic enzyme to support fatty acid synthesis.

Essential Fatty Acids

Fatty acids that cannot be synthesized de novo by humans due to the lack of desaturase enzymes capable of inserting double bonds beyond carbon atom 9; specifically linoleic acid ($18:2(9,12)$, precursor of $\omega\text{-}6$ arachidonic acid) and linolenic acid ($18:3(9,12,15)$, precursor of $\omega\text{-}3$ fatty acids).

Adipose Triglyceride Lipase (ATGL)

The initial lipase in adipocyte lipolysis that hydrolyzes a triacylglycerol (TG) molecule to a diacylglycerol (DAG) and a free fatty acid, preceding cleavage by hormone-sensitive lipase (HSL) and monoacylglycerol lipase.

Phospholipase C (PLC)

A membrane-associated phosphodiesterase that cleaves phosphatidylinositol 4,5-bisphosphate ($\text{PIP}_2$) into diacylglycerol (DAG), which stimulates protein kinase C (PKC), and inositol 1,4,5-trisphosphate ($\text{IP}_3$), which triggers calcium release from the endoplasmic reticulum.

Gangliosides

Acidic glycosphingolipids composed of a sphingosine backbone, a fatty acid attached via an amide bond, and a branched oligosaccharide chain that contains at least one negatively charged sialic acid (N-acetylneuraminic acid, NANA).

Ornithine Transcarbamoylase (OTC) Deficiency

An X-linked inborn error of the urea cycle characterized by an inability to combine carbamoyl phosphate with ornithine to form citrulline, leading to severe hyperammonemia, brain swelling, coma, and fatal encephalopathy.

PEST Sequence

A peptide sequence motif enriched in proline (Pro), glutamate (Glu), serine (Ser), and threonine (Thr) residues that acts as an internal signal directing proteins toward rapid intracellular proteolysis.

N-Terminal Rule

The regulatory principle dictating that the metabolic half-life of a protein is heavily influenced by its N-terminal residue; amino acids such as Phe, Leu, Asp, Lys, and Arg confer short half-lives, whereas Met, Ser, Ala, Thr, Val, and Gly confer longer stability.

Carbamoyl Phosphate Synthetase 1 (CPS-1)

The initial, rate-limiting mitochondrial enzyme of the urea cycle that condenses $\text{NH}_3$, $\text{CO}_2$, and $2\,\text{ATP}$ into carbamoyl phosphate; it requires allosteric activation by N-acetylglutamate and increases in concentration with high-protein intake or starvation.

Alanine Cycle

An interorgan cycle where muscle transaminates pyruvate to alanine for transport through blood to the liver; the liver deaminates alanine to feed nitrogen into the urea cycle and uses the carbon skeleton for gluconeogenesis to replenish blood glucose.

Phenylketonuria (PKU)

An autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase (or its cofactor tetrahydrobiopterin, $\text{BH}_4$), resulting in elevated blood phenylalanine and excretion of phenylpyruvate, phenyllactate, and phenylacetate.

Maple Syrup Urine Disease (MSUD)

An inherited metabolic disease caused by a deficiency in the branched-chain $\alpha$-keto acid dehydrogenase complex, blocking the normal oxidative decarboxylation and degradation of leucine, isoleucine, and valine.

Alkaptonuria

A genetic condition caused by deficiency of homogentisate oxidase in the tyrosine catabolic pathway, resulting in the systemic accumulation of homogentisate, which oxidizes to produce characteristic dark or black urine.

Albinism

A congenital disorder stemming from a deficiency in tyrosinase, the rate-limiting copper-containing enzyme required to convert tyrosine to DOPA quinone and downstream melanin pigments.

Glycogen Branching Enzyme

An enzyme involved in glycogenesis that removes an $\alpha\text{-}1,4\text{-linked}$ segment of approximately 7 glucosyl units from an outer chain and reattaches it via an $\alpha\text{-}1,6\text{-linkage}$ to create a new branch point.

Glycogen Debranching Enzyme

A bifunctional enzyme required for complete glycogen breakdown containing 4-$\alpha$-glucanotransferase activity (shifting a trisaccharide unit from a branch to a main chain) and amylo-$\alpha\text{-}1,6\text{-glucosidase}$ activity (hydrolyzing the remaining single $\alpha\text{-}1,6\text{-linked}$ glucose residue into free glucose).

Glycogen Phosphorylase

The principal phosphorolytic enzyme of glycogen degradation that cleaves terminal $\alpha\text{-}1,4\text{-glycosidic bonds}$ using inorganic phosphate to release glucose 1-phosphate, halting four residues away from an $\alpha\text{-}1,6$ branch point.

Hers' Disease (Type VI Glycogen Storage Disease)

A glycogen storage disorder caused by a deficiency of hepatic glycogen phosphorylase, resulting in pronounced hepatomegaly due to glycogen accumulation and demonstrating that phosphorylase functions to degrade glycogen in vivo.

Von Gierke's Disease (Type I Glycogen Storage Disease)

A severe glycogen storage disease caused by a genetic deficiency of glucose 6-phosphatase, which prevents the liver from dephosphorylating glucose 6-phosphate to free glucose during glycogenolysis and gluconeogenesis.

Cori's Disease (Type III Glycogen Storage Disease)

A glycogen storage disorder caused by a deficiency in the glycogen debranching enzyme, resulting in the abnormal intracellular buildup of branched glycogen polymers with short outer branches (limit dextrins).

Pompe's Disease (Type II Glycogen Storage Disease)

A fatal glycogen storage disease caused by a defect in lysosomal $\alpha\text{-}1,6\text{-glucosidase}$ (acid maltase), leading to pathological accumulation of glycogen inside lysosomes across multiple tissues.

Phosphorylase b Kinase

A regulatory protein kinase that converts inactive glycogen phosphorylase b into active phosphorylase a by targeted phosphorylation; its own catalytic activity is stimulated by protein kinase A (PKA) phosphorylation and by $\text{Ca}^{2+}$ binding.

Glucose 6-Phosphate Dehydrogenase (G6PD) Deficiency

The most common human enzymatic defect, which reduces $\text{NADPH}$ production via the pentose phosphate pathway, depleting reduced glutathione (GSH) and rendering red blood cell membranes susceptible to lipid peroxidation and drug-induced acute hemolytic anemia.

Transketolase

A thiamine pyrophosphate (TPP)-dependent enzyme in the non-oxidative branch of the pentose phosphate pathway that catalyzes reversible two-carbon transfers between ketose donor and aldose acceptor sugars.