Biochemistry Flashcards: Glycolysis, Gluconeogenesis, Pentose Phosphate Pathway, Glycogen Metabolism, and the Citric Acid Cycle

Comprehensive vocabulary flashcards covering Glycolysis, Gluconeogenesis, the Pentose Phosphate Pathway, Glycogen Metabolism, and the Citric Acid Cycle from Lehninger Principles of Biochemistry.

Coenzyme

An organic nonprotein molecule that binds with an apoenzyme to form a catalytically active holoenzyme, assisting in enzyme-catalyzed reactions by serving as an intermediate carrier of electrons or functional groups.

Prosthetic Group

A coenzyme or cofactor that is covalently or very tightly bonded to an enzyme protein molecule.

Glycolysis

An almost universal pathway of glucose catabolism in which one molecule of glucose is degraded through ten enzyme-catalyzed reactions to yield two molecules of pyruvate, conserving energy as $\text{ATP}$ and $\text{NADH}$.

Isozymes

Two or more enzymes that catalyze the same chemical reaction but are encoded by different genes and exhibit distinct kinetic or regulatory properties.

Preparatory Phase

The first phase of glycolysis (steps 1 to 5) in which two molecules of $\text{ATP}$ are invested to phosphorylate hexose sugar intermediates, splitting glucose into two molecules of glyceraldehyde 3-phosphate.

Payoff Phase

The second phase of glycolysis (steps 6 to 10) in which two triose phosphate molecules are converted into two pyruvate molecules, yielding four $\text{ATP}$ (net 2 $\text{ATP}$) and two $\text{NADH}$.

Substrate-Level Phosphorylation

The formation of $\text{ATP}$ or $\text{GTP}$ by direct phosphoryl group transfer from a high-energy soluble metabolic intermediate to $\text{ADP}$ or $\text{GDP}$.

Fermentation

A general term for anaerobic processes that extract energy as $\text{ATP}$ from glucose or other nutrients without consuming oxygen or changing net concentrations of $\text{NAD}^+$ or $\text{NADH}$.

Lactic Acid Fermentation

The anaerobic process in which pyruvate accepts electrons from $Streams of \text{NADH}$and is reduced to lactate by lactate dehydrogenase, regenerating$\text{NAD}^+$$ for continued glycolysis.

Ethanol Fermentation

The two-step anaerobic pathway in yeast and other microorganisms where pyruvate is decarboxylated to acetaldehyde and then reduced to ethanol, regenerating $\text{NAD}^+$.

Pyruvate Decarboxylase

A TPP- and $\text{Mg}^{2+}$-dependent enzyme that catalyzes the irreversible decarboxylation of pyruvate to acetaldehyde during ethanol fermentation.

Thiamine Pyrophosphate (TPP)

A coenzyme derived from vitamin $\text{B}_1$ containing a thiazolium ring that ionizes to form a carbanion capable of cleaving carbon-carbon bonds adjacent to carbonyl groups.

Gluconeogenesis

The pathway that converts pyruvate and related three- and four-carbon non-carbohydrate precursors into free glucose, occurring mainly in the liver of mammals.

Pyruvate Carboxylase

A mitochondrial enzyme that uses $\text{ATP}$ and the coenzyme biotin to convert pyruvate and $\text{HCO}_3^-$ into oxaloacetate during the first bypass reaction of gluconeogenesis.

Phosphoenolpyruvate Carboxykinase (PEPCK)

The enzyme that converts oxaloacetate to phosphoenolpyruvate ($\text{PEP}$) using $\text{GTP}$ and releasing $\text{CO}_2$ in gluconeogenesis.

Fructose 1,6-Bisphosphatase-1 (FBPase-1)

The regulatory enzyme of gluconeogenesis that bypasses the PFK-1 step of glycolysis by hydrolyzing fructose 1,6-bisphosphate to fructose 6-phosphate.

Glucose 6-Phosphatase

An enzyme located in the lumen of the endoplasmic reticulum of liver, kidney, and small intestine cells that hydrolyzes glucose 6-phosphate to yield free blood glucose.

Glucogenic Amino Acids

Amino acids whose carbon skeletons can be catabolized into pyruvate or citric acid cycle intermediates capable of net conversion into glucose.

Glyceroneogenesis

An abbreviated version of gluconeogenesis in adipocytes that converts pyruvate to dihydroxyacetone phosphate, which is then reduced to glycerol 3-phosphate for triacylglycerol synthesis.

Hexokinase IV (Glucokinase)

A liver-specific hexokinase isozyme characterized by a high $K_m$ for glucose, lack of product inhibition by glucose 6-phosphate, and regulation by nuclear sequestration.

Phosphofructokinase-1 (PFK-1)

The primary committed-step enzyme of glycolysis that catalyzes the transfer of a phosphoryl group from $\text{ATP}$ to fructose 6-phosphate to form fructose 1,6-bisphosphate.

Fructose 2,6-Bisphosphate (F2,6BP)

A potent allosteric effector synthesized by PFK-2 that simultaneously activates PFK-1 to stimulate glycolysis and inhibits FBPase-1 to suppress gluconeogenesis.

ChREBP

Carbohydrate Response Element Binding Protein, a transcription factor that enters the nucleus when dephosphorylated by PP2A to turn on gene synthesis for carbohydrate and lipid production.

Pentose Phosphate Pathway

An alternative pathway of glucose oxidation that produces $\text{NADPH}$ for reductive biosynthesis and pentose phosphates (such as ribose 5-phosphate) for nucleotide synthesis.

Glucose 6-Phosphate Dehydrogenase (G6PD)

The rate-limiting enzyme of the oxidative phase of the pentose phosphate pathway that oxidizes glucose 6-phosphate to 6-phosphoglucono-$\delta$-lactone while reducing $\text{NADP}^+$ to $\text{NADPH}$.

Transketolase

A TPP-dependent enzyme in the nonoxidative phase of the pentose phosphate pathway that catalyzes the transfer of a two-carbon ketose fragment to an aldose acceptor.

Transaldolase

An enzyme in the nonoxidative phase of the pentose phosphate pathway that utilizes a protonated Schiff base to transfer a three-carbon fragment from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate.

Glycogen

A polymeric storage form of glucose in animals consisting of ($\alpha 1 \rightarrow 4$)-linked glucose chains with ($\alpha 1 \rightarrow 6$)-linked branches, stored mainly in muscle and liver.

Glycogen β-Granule

A cytosolic granule containing a dimeric glycogenin core surrounded by up to 12 tiers of branched glucose chains and associated metabolic enzymes.

Glycogenolysis

The metabolic breakdown of cellular glycogen to glucose 1-phosphate.

Glycogenesis

The metabolic pathway for the synthesis of glycogen from glucose.

Glycogen Phosphorylase

A PLP-dependent enzyme that catalyzes phosphorolytic cleavage of ($\alpha 1 \rightarrow 4$) glycosidic linkages at the nonreducing ends of glycogen to produce glucose 1-phosphate.

Debranching Enzyme

A bifunctional enzyme containing transferase and ($\alpha 1 \rightarrow 6$) glucosidase activities that rearranges and removes branch points during glycogen degradation.

Phosphoglucomutase

An isomerase enzyme that catalyzes the reversible conversion of glucose 1-phosphate to glucose 6-phosphate via a glucose 1,6-bisphosphate intermediate.

UDP-Glucose

An activated sugar nucleotide formed from glucose 1-phosphate and $\text{UTP}$ that serves as the immediate donor of glucose residues in glycogen synthesis.

Glycogen Synthase

An enzyme that catalyzes the transfer of glucose residues from UDP-glucose to a nonreducing end of a glycogen chain, forming ($\alpha 1 \rightarrow 4$) glycosidic bonds.

Glycogen-Branching Enzyme

An enzyme that forms ($\alpha 1 \rightarrow 6$) branch points by transferring terminal blocks of 6 or 7 glucose residues to the C-6 hydroxyl group of an internal glucose residue.

Glycogenin

A homodimeric protein that functions as both a primer and an autocatalytic enzyme, attaching initial glucose residues to its Tyr194 residue to initiate a new glycogen molecule.

Phosphoprotein Phosphatase 1 (PP1)

An enzyme that dephosphorylates glycogen phosphorylase and glycogen synthase, stimulating glycogen synthesis while inhibiting glycogen breakdown.

Glycogen Synthase Kinase 3 (GSK3)

A kinase that phosphorylates and inactivates glycogen synthase a, acting hierarchically after a priming phosphorylation by casein kinase II (CKII).

Pyruvate Dehydrogenase (PDH) Complex

A highly ordered cluster of three enzymes ($E_1, E_2, E_3$) and five coenzymes in the mitochondrial matrix that oxidizes pyruvate to acetyl-CoA and $\text{CO}_2$.

Substrate Channeling

The direct passage of chemical intermediates from one enzyme active site to another within a multienzyme complex without releasing them into free solution.

Coenzyme A (CoA-SH)

A coenzyme containing a reactive thiol (—SH) group that forms high-energy thioester linkages with acyl groups, serving as a universal acetyl and acyl group carrier.

Citric Acid Cycle

An eight-step cyclic pathway in the mitochondrial matrix that oxidizes acetyl-CoA to $\text{CO}_2$, producing $\text{NADH}$, $\text{FADH}_2$, and $\text{GTP}$ or $\text{ATP}$.

Citrate Synthase

The first enzyme of the citric acid cycle that catalyzes the exergonic condensation of acetyl-CoA with oxaloacetate to form citrate via a citroyl-CoA intermediate.

Aconitase

An iron-sulfur protein that catalyzes the reversible hydration/dehydration isomerization of citrate to isocitrate through the intermediate cis-aconitate.

Isocitrate Dehydrogenase

The enzyme that catalyzes the oxidative decarboxylation of isocitrate to $\alpha$-ketoglutarate, generating $\text{CO}_2$ and $\text{NADH}$ or $\text{NADPH}$.

α-Ketoglutarate Dehydrogenase Complex

A multienzyme complex homologous to the PDH complex that catalyzes the oxidative decarboxylation of $\alpha$-ketoglutarate to succinyl-CoA and $\text{CO}_2$.

Succinyl-CoA Synthetase

An enzyme that breaks the high-energy thioester bond of succinyl-CoA to form succinate, driving substrate-level phosphorylation of $\text{GDP}$ or $\text{ADP}$.

Succinate Dehydrogenase

An integral mitochondrial inner membrane flavoprotein containing iron-sulfur clusters that oxidizes succinate to fumarate while reducing $\text{FAD}$ to $\text{FADH}_2$.

Amphibolic Pathway

A metabolic pathway, such as the citric acid cycle, that functions in both catabolic (energy-yielding) and anabolic (biosynthetic) processes.

Glyoxylate Cycle

A pathway in plants, fungi, and microorganisms that bypasses the decarboxylation steps of the citric acid cycle to allow net conversion of acetate or fatty acids into glucose.

Anaplerotic Reactions

Enzymatic reactions that replenish intermediates of a metabolic pathway (such as the citric acid cycle) when they are shunted away for biosynthetic processes.

Metabolon

A supramolecular multienzyme complex held together by noncovalent interactions that ensures efficient substrate channeling between sequential metabolic steps.

Oncometabolites

Metabolic intermediates (such as accumulated lactate, succinate, or 2-hydroxyglutarate) that stimulate tumor growth by acting through plasma membrane receptors or signaling pathways.

Coenzyme

An organic nonprotein molecule that binds with an apoenzyme to form the active holoenzyme, assisting in the catalysis of a reaction by acting as an intermediate carrier of electrons or functional groups.

Prosthetic Group

A coenzyme or cofactor that is covalently bonded to its enzyme.

Isozymes

Two or more enzymes in the same organism that catalyze the same reaction but are encoded by different genes.

Glycolysis

An almost universal pathway of glucose catabolism in which one molecule of glucose is degraded in ten enzyme-catalyzed reactions to yield two molecules of pyruvate, conserving energy as $2\text{ ATP}$ and $2\text{ NADH}$.

Preparatory Phase of Glycolysis

The first phase of glycolysis (steps 1–5) in which $2\text{ ATP}$ are consumed to phosphorylate hexose intermediates, converting glucose into two molecules of glyceraldehyde 3-phosphate.

Payoff Phase of Glycolysis

The second phase of glycolysis (steps 6–10) in which two molecules of glyceraldehyde 3-phosphate are oxidized to two pyruvate molecules, conserving energy as $4\text{ ATP}$ ($2\text{ ATP}$ net) and $2\text{ NADH}$.

Substrate-Level Phosphorylation

The synthesis of ATP (or GTP) by the direct enzymatic transfer of a high-energy phosphoryl group from a phosphorylated metabolic intermediate to ADP (or GDP).

Fermentation

A general term for anaerobic metabolic processes that extract energy as ATP without consuming oxygen or changing the net cellular concentration of $\text{NAD}^+$ or $\text{NADH}$.

Lactic Acid Fermentation

An anaerobic pathway in which pyruvate accepts electrons from $\text{NADH}$ and is reduced to lactate by lactate dehydrogenase, regenerating the $\text{NAD}^+$ needed for glycolysis.

Ethanol Fermentation

A two-step anaerobic pathway in yeast and other microorganisms where pyruvate is decarboxylated to acetaldehyde by pyruvate decarboxylase and then reduced to ethanol by alcohol dehydrogenase, regenerating $\text{NAD}^+$.

Gluconeogenesis

A universal pathway that converts pyruvate and related three- and four-carbon non-carbohydrate precursors into glucose, utilizing seven reversible reactions of glycolysis and bypassing three irreversible steps.

Glucogenic Amino Acids

Amino acids whose carbon skeletons can be deaminated and converted into pyruvate or citric acid cycle intermediates capable of net conversion to glucose.

Glyceroneogenesis

An abbreviated version of gluconeogenesis in adipocytes that converts pyruvate to dihydroxyacetone phosphate, followed by reduction to glycerol 3-phosphate.

Futile Cycle

A scenario where two opposing metabolic pathways (such as glycolysis and gluconeogenesis) operate simultaneously, consuming ATP without accomplishing chemical or biological work.

Hexokinase IV (Glucokinase)

A liver-specific isozyme of hexokinase with a high $K_m$ for glucose ($10\text{ mM}$) that is not inhibited by glucose 6-phosphate and is regulated by sequestration inside the nucleus.

Glucagon

A pancreatic hormone released in response to low blood glucose that signals the liver to stimulate glycogen breakdown and gluconeogenesis while inhibiting glycolysis.

Insulin

A pancreatic hormone released in response to high blood glucose that signals the liver and peripheral tissues to consume glucose for energy, store it as glycogen, and synthesize fatty acids.

ChREBP (Carbohydrate Response Element Binding Protein)

A transcription factor expressed in liver, kidney, and adipose tissue that, upon dephosphorylation by PP2A, enters the nucleus to activate genes encoding enzymes for carbohydrate and lipid synthesis.

Pentose Phosphate Pathway

An alternative pathway of glucose 6-phosphate oxidation that yields pentose phosphates for nucleotide synthesis and $\text{NADPH}$ for reductive biosynthetic reactions.

Transketolase

A TPP-dependent enzyme in the nonoxidative phase of the pentose phosphate pathway that catalyzes the transfer of a two-carbon fragment from a ketose donor to an aldose acceptor.

Transaldolase

An enzyme in the nonoxidative phase of the pentose phosphate pathway that stabilizes a carbanion intermediate using a protonated Schiff base to transfer a three-carbon fragment from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate.

Phosphoglycomutase

An enzyme that catalyzes the reversible interconversion of glucose 1-phosphate and glucose 6-phosphate.

$\alpha$-Amylase

A digestive enzyme present in saliva and pancreatic juice that hydrolyzes internal ($\alpha1\rightarrow 4$) glycosidic linkages of dietary starch and glycogen.

Galactosemia

A group of genetic metabolic diseases caused by a deficiency in any of the enzymes required to convert galactose into glucose 1-phosphate.

Glycogen $\beta$-Granule

A cytosolic granule containing a central glycogenin dimer surrounded by multiple tiers of glucose residues linked in ($\alpha1\rightarrow 4$) chains with ($\alpha1\rightarrow 6$) branches.

Glycogen $\alpha$-Granule

A protein-rich liver granule composed of 20 to 40 clustered glycogen $\beta$-granules that releases glucose more slowly than individual $\beta$-granules.

Glycogenolysis

The intracellular breakdown of glycogen to glucose 1-phosphate.

Glycogenesis

The metabolic pathway for the synthesis of glycogen from glucose 6-phosphate.

Glycogen Phosphorylase

A pyridoxal phosphate (PLP)-dependent enzyme that catalyzes phosphorolytic cleavage of ($\alpha1\rightarrow 4$) glycosidic bonds at the nonreducing ends of glycogen to produce glucose 1-phosphate.

Debranching Enzyme

A bifunctional enzyme that moves three glucose residues from a branch to a nearby nonreducing end and hydrolyzes the remaining ($\alpha1\rightarrow 6$)-linked glucose branch point to release free glucose.

Sugar Nucleotide

An activated form of a sugar (e.g., UDP-glucose) in which the anomeric carbon is attached to a nucleotide via a phosphate ester bond, serving as a donor in glycosyl transfer reactions.

Glycogenin

A homodimeric protein that acts as both the primer and the autocatalytic enzyme for assembling the initial eight glucose residues of a new glycogen chain on its Tyr194 residue.

Glycogen-Branching Enzyme

An enzyme (also called amylo (1$\rightarrow$4) to (1$\rightarrow$6) transglycosylase) that transfers a terminal 6–7 glucose fragment to the C-6 hydroxyl group of a glucose residue on the same or another chain.

Phosphoprotein Phosphatase 1 (PP1)

An enzyme that removes phosphoryl groups from glycogen phosphorylase a (inactivating it to form b) and glycogen synthase b (activating it to form a).

Glycogen Synthase Kinase 3 (GSK3)

A kinase that phosphorylates and inactivates glycogen synthase a, acting hierarchically after a priming phosphorylation by casein kinase II.

Glycogen-Targeting Protein

A regulatory scaffolding subunit of PP1 (such as $G_M$) that binds glycogen, PP1, phosphorylase kinase, glycogen phosphorylase, and glycogen synthase.

Pyruvate Dehydrogenase (PDH) Complex

A multienzyme complex ($E_1$, $E_2$, $E_3$) in the mitochondrial matrix that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA and $CO_2$.

Mitochondrial Pyruvate Carrier (MPC)

An $H^+$-coupled pyruvate-specific symporter located in the inner mitochondrial membrane that transports pyruvate into the matrix.

Substrate Channeling

The direct transfer of metabolic intermediates between active sites of adjacent enzymes in a complex without releasing them into free solution.

Amphibolic Pathway

A metabolic pathway, such as the citric acid cycle, that functions in both catabolic (energy-yielding) and anabolic (precursor-generating) processes.

Anaplerotic Reactions

Enzymatic reactions (such as pyruvate carboxylase) that replenish intermediates withdrawn from a metabolic pathway like the citric acid cycle.

Glyoxylate Cycle

A metabolic pathway in plants, fungi, and microorganisms that bypasses the two decarboxylation steps of the citric acid cycle to allow net conversion of acetate to carbohydrates.

Oncometabolites

Metabolic intermediates (such as accumulated lactate, succinate, or 2-hydroxyglutarate) that stimulate tumor growth by acting through cell surface receptors or altering gene expression.

Metabolon

A supramolecular, noncovalently bound multienzyme complex that channels sequential products from one enzyme directly to the next.