ATP: Energy Currency of the Cell

• ATP is produced by the oxidation of food and captures energy as high-energy phosphate bonds
• ATP is not stored, it is continuously synthesized and used
• ATP is produced by oxidative phosphorylation in the Mitochondrial Electron Transport System (ETS), also named the Respiratory Chain
• ATP is produced by substrate-level phosphorylation, involving the direct transfer of phosphate to ADP from a high-energy molecule (creatine phosphate)

Functions of ATP

• ATP supplies energy for biochemical processes
• ATP typically supplies energy by group transfer (phosphoryl group)
• Glutamine synthesis requires energy that is supplied by ATP

ATP Hydrolysis

• Low-energy bonds yield a standard free energy (ΔG) of ≤ 5 kcal/mol upon destruction
• High-energy bonds yield a standard free energy (ΔG) higher than 5 kcal/mol upon destruction
• ATP to ADP releases -7.3 kcal/mol of ATP (-30.5 kJ/mol of ATP)
• ATP to AMP releases -10.9 kcal/mol of ATP (-45.6 kJ/mol of ATP)
• Pyrophosphate (PPi) is hydrolyzed to two inorganic phosphates (2Pi) by pyrophosphatase, producing 4.0 kcal/mol of ATP

High and Low-Energy Compounds

• High-energy phosphate compounds include phosphoenolpyruvate (PEP), 1,3-bisphosphoglycerate, creatine phosphate, nucleoside monophosphates (e.g., AMP, GMP), nucleoside diphosphates (e.g., ADP, GDP), nucleoside triphosphates (e.g., ATP, GTP)
• Low-energy phosphate compounds include sugar phosphates (e.g., Glucose-6-P, Fructose-6-P), and Glycolysis intermediates
• ADP and ATP bind with Mg2+ ions to form MgADP and MgATP complexes in the cytosol

Nucleotides for Metabolic Reactions

• Adenosinetriphosphate (ATP), cyclic adenosinemonophosphate (cAMP), Flavin mononucleotide (FMN), Flavin adeninedinucleotide (FAD), Nicotinamide adeninedinucleotide (NAD), Nicotinamide adeninedinucleotide phosphate (NADP), Uridine triphosphate (UTP), Coenzyme A (CoA) (CoASH)

ATP Composition and Function

• ATP consists of adenine-ribose-PPP, having two high-energy phosphate bonds and one low-energy phosphate bond
• ATP is negatively charged
• Formation of phosphoanhydride bonds through condensation reactions
• Nucleotides combine with phosphodiester bonds to produce nucleic acids
• Mononucleotides are also named as: Cytidylic acid, Uridylic acid, Thymidylic acid, Adenylic acid, Guanylic acid, Inosinic acid
• Deoxy derivatives of nucleotides have 2-deoxy-D-ribose as their pentose

Nucleotide Composition

• A nucleotide composes of a nitrogenous heterocyclic base, pentose, and phosphate.
• A nucleoside composes of a nitrogenous heterocyclic base and pentose
• Purines include Adenine and Guanine
• Pyrimidines include Cytosine, Uracil, and Thymine

ATP in Metabolic Processes

• Initially, a phosphoryl group is transferred to enzyme-bound glutamate to produce enzyme-bound glutamyl phosphate
• Phosphoryl is (-PO3)
• Examples metabolic processes using ATP: Muscle contraction, active transport through membranes, activation of molecules (e.g., activation of fatty acids)
• Activation of fatty acids requires energy that is supplied by ATP
• Glucose undergoes metabolic reactions after conversion to its phosphate derivative, catalyzed by ATP
• Phosphorylation reactions are carried out by kinases, dephosphorylation reactions are carried out by phosphatases
• Monosaccharides in the liver are converted to glucose over phosphate derivatives by phosphatases
• Conversion of amino acids to one another requires ATP as well as UTP

Cyclic AMP

• Cyclic AMP (cAMP) is the second messenger for some hormones
• cAMP is produced from ATP by adenylyl cyclase, an enzyme existing in plasma membranes

Flavin Mononucleotide and Adenine Dinucleotide

• Flavin mononucleotide (FMN) and flavin adeninedinucleotide (FAD) contain riboflavin (vitamin B2)
• FMN contains dimethylisoalloxazine (flavin part), ribitol (sugar alcohol), and phosphate
• FAD contains dimethylisoalloxazine ribitol, phosphate, adenine, ribose, phosphate
• FMN and FAD are prosthetic groups of oxidoreductases, and enzymes containing these are called flavoenzymes or flavoproteins
• FMN and FAD are coenzymes derived from vitamin B2 (riboflavin)

Nicotinamide Dinucleotides

• Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate include nicotinamide, ribose, phosphate, and adenine
• NAD and NADP are coenzymes of oxidoreductases
• Uridine triphosphate (UTP) activates molecules in the form of UDP, before incorporation into biochemical processes
• UDP activates molecules
• Examples: UDP-galactose (lactose synthesis), UDP-amino sugar (synthesis of glycosaminoglycans), UDP-glucuronic acid (xenobiotic metabolism), UDP-glucose (heme metabolism, glycogen synthesis)

Coenzyme A

• Coenzyme A (CoA) contains 4'-phosphopantetheine
• 4'-phosphopantetheine includes adenosine-3'-phosphate, pyrophosphate, pantothenic acid, and β-mercaptoethylamine
• Pantothenic acid (vitamin B5) is a component of CoA
• The functional group of CoA is -SH (thiol, mercapto, sulfhydryl)
• Its thiol (-SH) group carries fatty acids as acyl groups
• CoA also carries other carboxylic acids as acyl groups, such as succinyl-CoA
• Coenzyme A carries acyl groups

Synthetases versus Synthases

• If synthesis of a molecule requires energy (ATP), the enzyme is named synthetase
• If synthesis of a molecule does not require energy, the enzyme is named synthase