Nucleotides and Nucleic Acids

• Nucleotides combine via phosphodiester bonds to produce nucleic acids.
• There are 2 nucleotides: Inosine monophosphate and Xanthosine monophosphate, that do not exist in the structure of nucleic acids.
• Mononucleotides are Cytidylic acid, Uridylic acid, Thymidylic acid, Adenylic acid, Guanylic acid, and Inosinic acid.
• In deoxy derivatives of nucleotides, Pentose is 2-deoxy-D-ribose.
• A nucleotide is composed of a nitrogenous heterocyclic base, pentose, and phosphate.
• A nucleoside is composed of a nitrogenous heterocyclic base and a pentose.
• Pyrimidines are Cytosine, Uracil, and Thymine.
• Purines are Adenine, and Guanine.
• Some nucleotides are significant for metabolic reactions: Adenosinetriphosphate (ATP), Cyclic adenosinemonophosphate (cAMP), Flavin mononucleotide (FMN), Flavin adeninedinucleotide (FAD), Nicotinamide adeninedinucleotide (NAD), Nicotinamide adeninedinucleotide phosphate (NADP), Uridine triphosphate (UTP), and Coenzyme A (CoA) (CoASH).

ADENOSINETRIPHOSPHATE (ATP)

• Structure of ATP: Adenine-ribose-PPP
• ATP has two high-energy phosphate bonds and one low-energy phosphate bond.
• P: Low-energy phosphate bond
• ~P: High-energy phosphate bond
• ATP is negatively charged, ATP4-.
• Low-energy bonds yield standard free energy (ΔG°) ≤ 5kcal/mol.
• High-energy bonds yield standard free energy (ΔG°) > 5kcal/mol.
• ΔG° releases as a result of hydrolysis of phosphate bonds of ATP.
• ATP + H2O -> ADP + Pi ΔG° = -7.3 kcal / mol of ATP (-30.5 kJ / mol of ATP) releases 1 high-energy phosphate
• ATP + H2O -> AMP + PPi ΔG° = -10.9 kcal / mol of ATP (-45.6 kJ / mol of ATP) releases 2 high-energy phosphates
• P is phosphate (-OPO3-).
• PPi is pyrophosphate.
• PPi -> 2Pi
• Pyrophosphate (PPi) is further hydrolyzed to two inorganic phosphates (2Pi) by pyrophosphatase, producing 4.0 kcal / mol of ATP.
• Both high-energy bonds of ATP are hydrolyzed to yield free energy of 14.9 kcal / mol of ATP (10.9 kcal / mol of ATP + 4.0 kcal / mol of ATP).

High-energy phosphate compounds

• Phosphoenolpyruvate (PEP), 1,3-biphosphoglycerate, and creatine phosphate are high-energy phosphate compounds.
• Nucleoside diphosphates such as ADP and GDP and nucleoside triphosphates such as ATP and GTP are high-energy phosphate compounds.
• Sugar phosphates such as Glucose-6-P and fructose-6-P and nucleoside monophosphates such as AMP and GMP are low-energy phosphate compounds.
• Glycolysis intermediates are high-energy phosphate compounds.
• ADP and ATP bind with Mg2+ ions in the cytosol to form MgADP+ and MgATP2- complexes.

Production of ATP

• Oxidation of foodstuffs produces energy.
• ATP conserves or captures this energy as a high-energy phosphate bond.
• ATP is not stored; it is continuously synthesized and used as ATP turnover is rapid.
• It is more accurate to describe ATP as conserved rather than stored.
• ATP is produced by oxidative phosphorylation in the mitochondrial electron transport system (ETS), also named the respiratory chain and substrate-level phosphorylation, which involves the direct transfer of phosphate to ADP from a high-energy molecule.
• ATP is also produced from high-energy phosphate compounds like creatine phosphate.
• ATP supplies energy for biochemical processes, typically by group transfer of a phosphoryl group.

Glutamine Synthetase Mechanism

• ATP supplies energy by group transfer (phosphoryl group) instead of simple hydrolysis.
• ATP transfers a phosphate group to glutamate, forming an enzyme-bound intermediate called glutamyl-phosphate.
• Ammonia attacks this intermediate, releasing phosphate and forming glutamine.
• Glutamate is converted to glutamine via glutamine synthetase.
• The reaction is written as in (A), which indicates a simple hydrolysis of the energy supplied by ATP, but the real condition is indicated in (B).

Uridine Triphosphate (UTP)

• It has a structure of Uracil - ribose - PPP.
• UTP activates molecules in the form of UDP before they are incorporated into biochemical processes.
• UDP-galactose is used for lactose synthesis in mammary glands
• UDP-amino sugar: Conversion of amino sugar to one another to be used in syntheses of glycosaminoglycans, glycoproteins.
• UDP-glucuronic acid: Xenobiotic metabolism and heme metabolism
• UDP-glucose is for glycogen synthesis.
• Monosaccharides in the liver, after absorption, convert to glucose over their phosphate derivatives, which are produced by ATP or ATP with UTP.
• Conversion of amino sugars to one another requires ATP as well as UTP.

Nicotinamide Adenine Dinucleotide (NAD) and Nicotinamide Adenine Dinucleotide Phosphate (NADP)

• They are coenzymes of oxidoreductases. NAD and NADP are derived from vitamin B3 (Niasin).

Cyclic Adenosine Monophosphate (cAMP)

• It is the second messenger for some hormones.
• It is produced from ATP by adenylyl cyclase, an enzyme existing in the plasma membranes.

Flavin Mononucleotide (FMN) and Flavin Adeninedinucleotide (FAD)

• FMN and FAD are prosthetic groups of oxidoreductases (oxido-reduction enzymes).
• FMN and FAD containing enzymes are called flavoenzymes or flavoproteins.
• FMN and FAD are coenzymes derived from vitamin B2 (riboflavin).

Activation of Fatty Acids

• Initially, a phosphoryl group is transferred to enzyme-bound glutamate, thus enzyme-bound glutamyl phosphate is produced.
• Activation of fatty acids requires energy (endergonic reaction) and this energy is supplied by ATP.
• ATP donates phosphoryl (-P) group.
• Example of donation: Glucose undergoes metabolic reactions after it is converted to its phosphate derivative, and this step is conducted by ATP.
• This is a phosphorylation reaction carried out by kinases (phosphotransferases).
• Dephosphorylation reactions (removal of phosphoryl group) are carried out by phosphatases.
• Examples of metabolic processes whose energy is provided by ATP: muscle contraction, active transport through membranes, Activation of molecules like in the activation of fatty acids.
• Glucokinase, found in the liver and hexokinase, found in muscles, are necessary for glucose to convert to Glucose-6-phosphate.

Coenzyme A (CoA) (CoASH)

• It carries fatty acids as acyl groups through its thiol (-SH) group for oxidation of fatty acids and synthesis of triacylglycerols.
• It also carries other carboxylic acids as acyl groups, e.g., succinyl-CoA.
• The functional group of CoA is -SH (thiol, mercapto, sulphydryl) of β-mercaptoethylamine with the formula H2N –"CH2 –"CH2 –"SH.
• Coenzyme A carries acyl groups.
• Adenosine monophosphate (AMP) is holding a long vitamin B chain, at the end of which there is -SH.
• This hook grabs fatty acids and pulls them into the energy machine (mitochondria).
• When energy in the form of ATP is required for the synthesis of a molecule, the enzyme is called synthetase. If energy is not required, the enzyme is called synthase.