Bioenergetics & Metabolism

The cytosolic pathway in all mammalian cells for the catabolism of glucose (or glycogen) to pyruvate and lactate

What is Glycolysis?

Hexokinase

What is the enzyme responsible for converting glucose to glucose-6-phosphate?

Synthesis of glucose from noncarbohydrate sources

What is Gluconeogenesis?

Catalyze hydrolysis of glucose-6-phosphate to free glucose

What is Glucose-6-Phosphatase?

Stored form of glucose in liver cells (hepatocytes), muscle cells (myocytes), and kidney cells

What is Glycogen?

Biosynthesis of glycogen from glucose (ɑ-D-glucose)

What is Glycogenesis?

Enzyme catalyzing formation of glycosidic bond between C-1 of UDPGlc glucose and C-4 of glycogen terminal glucose

What is Glycogen Synthase?

Glycogen degradation to form glucose

What is Glycogenolysis?

Enzyme facilitating cleavage of the alpha ɑ(1,4) linkage of glycogen to produce glucose-1-phosphate

What is Glycogen Phosphorylase?

Alternative pathway for oxidation of glucose that produces NADPH, CO2 with no ATP consumed or produced

What is the Hexose Monophosphate Pathway?

Two mechanisms that convert fructose into glucose metabolites to be used in glycolysis

What is the Fructose-1-Phosphate Pathway?

Metabolism of galactose to form UDP-glucose and glucose-1-phosphate

What is Galactose Metabolism?

Enzyme utilized in the second step of Galactose Metabolism to convert Galactose-1-phosphate into UDP-Galactose

What is Galactose-1-Phosphate Uridyltransferase?

Glucose → Glucose-6-phosphate by phosphorylation using 1 ATP

What is Step 1 of Glycolysis: Phosphorylation of Glucose?

Fructose-6-phosphate → Fructose-1,6-bisphosphate by phosphorylation using 1 ATP; rate-limiting and irreversible step in glycolysis

What is Step 3 of Glycolysis: Phosphorylation of Fructose-6-Phosphate?

Most potent activator of phosphofructokinase-1 during the well-fed state

What is Fructose-2,6-bisphosphate?

Cleavage of fructose-1,6-bisphosphate into DHAP and glyceraldehyde-3-phosphate, catalyzed by aldolase A

What is Step 4 of Glycolysis: Cleavage of Fructose-1,6-Bisphosphate?

Oxidation of glyceraldehyde-3-phosphate producing NADH and 1,3-bisphosphoglycerate, catalyzed by glyceraldehyde 3-phosphate dehydrogenase

What is Step 6 of Glycolysis: Oxidation of Glyceraldehyde 3-Phosphate?

Irreversible conversion of phosphoenolpyruvate to pyruvate producing ATP, catalyzed by pyruvate kinase

What is Step 10 of Glycolysis: Pyruvate Formation?

Conversion of pyruvate to lactate under anaerobic conditions, catalyzed by lactate dehydrogenase

What is Alternative Fate of Pyruvate: Reduction to Lactate?

Pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3)

What enzymes form the Pyruvate Dehydrogenase Complex?

Glycerol, lactate, amino acids, and propionate

What are the main substrates for gluconeogenesis?

Carboxylation of pyruvate to oxaloacetate in gluconeogenesis, catalyzed by pyruvate carboxylase

What is a unique reaction of gluconeogenesis?

Protein initiating glycogenesis by catalyzing transfer of glucose residues to form glycogen primer

What is Glycogenin?

Enzyme with glucan transferase and 1,6-glucosidase activities to remove α(1,6) branches in glycogenolysis

What is the Debranching Enzyme?

Enzyme hydrolyzing glucose-6-phosphate to free glucose in the liver

What is Glucose-6-Phosphatase?

Production of NADPH for reductive anabolic pathways and ribose-5-phosphate for nucleotide biosynthesis

What is the significance of the Hexose Monophosphate Pathway?

NADP-dependent enzyme catalyzing the first step of the oxidative phase of Hexose Monophosphate Pathway

What is Glucose-6-Phosphate Dehydrogenase?

Enzyme phosphorylating fructose to fructose-1-phosphate in liver cells

What is Fructokinase?

Enzyme phosphorylating galactose to galactose-1-phosphate

What is Galactokinase?

Autosomal recessive disorder caused by uridyltransferase deficiency leading to galactosemia, jaundice, and mental retardation

What is Classic Galactosemia?

Study of energy transformation in living organisms

What is Bioenergetics?

Process all oxygen-utilizing cells use to transfer energy

What is Biologic Oxidation?

Series of functional proteins in mitochondria that harness energy to form ATP

What is the Electron Transport Chain (ETC)?

Process combining ETC function with chemiosmosis

What is Oxidative Phosphorylation?

Enzymes catalyzing removal of hydrogen using oxygen as acceptor

What are Oxidases?

Enzymes transferring hydrogen or electrons between substrates

What are Dehydrogenases?

Use of hydrogen peroxide as both electron donor and acceptor

What are Hydroperoxidases?

Enzymes incorporating oxygen into substrate molecules

What are Oxygenases?

Gain of electrons

What is Reduction?

Removal of electrons

What is Oxidation?

Donates electrons

What is a Reducing Agent?

Accepts electrons

What is an Oxidizing Agent?

Amount of energy available to do work

What is Gibbs Free Energy?

Spontaneous reaction

What does a negative ΔG indicate?

Non-spontaneous reaction needing energy input

What does a positive ΔG indicate?

Release energy, usually catabolic

What are exergonic reactions?

Requiring energy, usually anabolic

What are endergonic reactions?

Molecule acting as energy currency of the cell

What is ATP?

Reactions involving electron transfer

What are redox reactions?

Molecule donating electrons in redox

What is a reducing agent?

Molecule accepting electrons in redox

What is an oxidizing agent?

Tendency to gain electrons

What does a positive redox potential indicate?

Tendency to lose electrons

What does a negative redox potential indicate?

Location of ETC in the mitochondrion

What is the inner mitochondrial membrane?

Complex I transferring electrons from NADH to ubiquinone and pumping 4 H+

What is NADH-Q oxidoreductase?

Complex II transferring electrons from FADH2 to ubiquinone with no proton pumping

What is Succinate-Q reductase?

Mobile electron carrier that is not a protein

What is Ubiquinone (Q)?

Complex III transferring electrons from ubiquinol to cytochrome c and pumping 4 H+

What is Q-Cytochrome c oxidoreductase?

Complex IV transferring electrons to oxygen and producing water while pumping protons

What is Cytochrome c oxidase?

Molecular rotary motor synthesizing ATP using proton gradient

What is ATP Synthase?

Driving force for ATP synthesis in mitochondria

What is the proton gradient?

Blocks ETC complexes such as Rotenone, Antimycin A, and Cyanide

What are ETC inhibitors?

Dissipates proton gradient and bypassing ATP synthase

What are uncouplers?

Transfers electrons from cytosolic NADH to mitochondria

What is the Glycerol-3-Phosphate Shuttle?

Transfers high-energy phosphate groups rapidly in muscle and heart

What is the Creatine Phosphate Shuttle?

ATP synthesis driven by movement of protons through ATP synthase

What is Chemiosmosis?

Factor controlling rate of oxidative phosphorylation

What is ADP availability

Coupling with exergonic reactions

What allows endergonic reactions to proceed?

Two

How many high-energy phosphate bonds does ATP have?

Contain a carboxyl group and a long hydrocarbon chain

What are fatty acids?

In the cytosol of liver, kidney, brain, lung, mammary gland, and adipose tissue

Where does fatty acid synthesis occur?

Pyruvate decarboxylation

What is the precursor for fatty acid synthesis?

Carboxylation of acetyl-CoA to malonyl-CoA

What is the first step in fatty acid synthesis?

Acetyl-CoA carboxylase; regulated by citrate and palmitoyl-CoA

What catalyzes carboxylation of acetyl-CoA?

Fatty acid synthase complex

What synthesizes saturated fatty acids like palmitate?

NADPH

What is the reducing agent in fatty acid synthesis?

Smooth endoplasmic reticulum

Where does fatty acid elongation and desaturation occur?

Δ9 desaturase

What enzyme adds double bonds at the Δ9 position?

Increased carbohydrate intake → increased glycolysis and lipogenesis

How does carbohydrate intake affect lipogenesis?

Low calorie diet → decreased acetyl-CoA and lipogenesis

How does low calorie diet affect lipogenesis?

Insulin increases glucose uptake and acetyl-CoA carboxylase activity

What is insulin’s role in fat metabolism?

Glycerol backbone with three fatty acid chains

What is triacylglycerol structure?

Glycerol kinase

What phosphorylates glycerol to glycerol-3-phosphate?

Lipolysis

What is sequential hydrolysis of triacylglycerols?

Acyl-CoA synthetase

What converts free fatty acid to acyl-CoA?

Carnitine palmitoyltransferase I

What transports acyl-CoA as acylcarnitine across the inner mitochondrial membrane?

β-oxidation

What breaks down acyl-CoA two carbons at a time?

Ketone bodies

What are alternative energy sources produced in the liver during fasting?

Mitochondria (production), extrahepatic tissues (usage)

Where are ketone bodies produced and used?

Diabetic ketoacidosis causing fruity acetone breath

What causes acetone breath smell?

Citrate shuttle

How is acetyl-CoA transported to cytosol?

Malonyl-CoA

What is the primary substrate added during fatty acid elongation?

Acetyl-CoA carboxylase deficiency → decreased fatty acid synthesis

What happens when acetyl-CoA carboxylase is deficient?

Acetyl-CoA

What is the common product of fat, carbohydrate, and protein metabolism?

Mitochondrial matrix

Where are the Citric Acid Cycle enzymes located?

Aerobic process

What type of process requires oxygen and is linked to oxidative phosphorylation?

Citrate

What is formed from the reaction of Acetyl-CoA and oxaloacetate?

Citrate synthase

What enzyme catalyzes the formation of citrate?

Aconitase

What enzyme converts citrate to isocitrate?