Energetics

Chapter 3

Energetics 

Formation and Role of ATP 

• Adenosine triphosphate (ATP) is a small molecule present in cells. It acts as a coenzyme and is a unit for transfer of metabolic energy. It transports chemical energy within cells. It carries energy to the place wherever needed. Most cellular functions need energy in order to carry out synthesis of proteins, synthesis of membranes, movement of the cell, cellular division, transport of various solutes etc. When ATP is hydrolyzed to ADP (adenosine diphosphate) and inorganic phosphate, the breakdown of covalent link of phosphate liberates energy which is used for metabolic activities. Structure of ATP is indicated in.

• There are three major mechanisms involved in biosynthesis of ATP. They are as follows:

•  Substrate level phosphorylation Oxidative phosphorylation in cellular respiration Photophosphorylation in photosynthesis.

• In structure of ATP, three phosphate groups are attached to 5 - carbon atom of the pentose sugar. The pentose is ribose in case of RNA and deoxyribose in case of DNA. It is the addition and removal of these phosphate groups which convert ATP, ADP and AMP. It was first artificially synthesized in laboratory in the year 1948. ATP is highly soluble in water and is stable between pH of 6.8-7.4. It is rapidly hydrolyzed by extremes of pH.

• water and is stable between pH of 6.8-7.4. It is rapidly hydrolyzed by extremes of pH. The standard amount of energy released from hydrolysis of ATP is as follows: ATP + H20 ADP + Pi It releases energy of 30.5 kJ/mol (7.3 kcal/mol) ATP + H204 AMP + PPI It releases energy of 45.6 kJ/mol (10.9 kcal/mol) ATP has several negatively charged groups in neutral solution. Hence, it chelates with metals with very high affinity. In cells, ATP mostly exists as a complex with Mg**.

• (a) Metabolism, Synthesis and Active Transport

• ATP is consumed in the cell by energy requiring (endergonic) processes and can be generated by energy releasing (exergonic) processes. Thus, it transfers energy between various metabolic reactions. It is the main energy source for majority of cellular reactions. This includes synthesis of DNA, RNA and proteins. It also plays an important role in transport of macromolecules across cell membrane e.g. exocytosis and endocytosis.

• (b) Roles in Cell Structure and Locomotion

• It is critically involved in maintaining cell structure by facilitating assembly and disassembly of the components of cytoskeleton. It is also required for contraction of actin and myosin which are proteins present in the muscle fibers. This process is one of the main energy requirements of animals and is needed for locomotion and respiration.

• (c) Cell Signaling

• Extracellular ATP (ATP) is also a signaling molecule. ATP, ADP and adenosine are recognized by purinergic receptors which are abundantly present in mammalian systems. Signaling role is important in CNS and peripheral nervous system (PNS). Activity dependent release of ATP from synapses, axons and glia activates purinergic membrane receptors known as P2. Unlike P2 receptors, ATP is not a strong agonist for Pı receptors. All adenosine receptors activate one sub-family of mitogen activated protein kinases. The actions of adenosine are antagonistic or synergistic to the actions of ATP. In CNS, adenosine modulates neural development, neuron and glial signaling and control immune system.

• (d) DNA and RNA Synthesis 

• Energetics DNA is a polymer of deoxy-ribonucleotides. The nucleotides are synthesized by action of an enzyme ribonucleotide reductase (RNR) on corresponding ribonucleotides. Regulation of RNR and related enzymes maintains a balance of dNTPs relative to each other and relative to NTPs in the cell. Very low NTP concentration inhibits DNA synthesis and repair and is lethal to the cell. Abnormal ratio of d NTPs is mutagenic due to increased possibility of the enzyme DNA polymerase incorporating wrong dNTP during DNA synthesis. Regulation or differential specificity of RNR is suggested to be a mechanism for alterations in relative sizes of intracellular d NTP pools under cellular stress like hypoxemia.

• (e) Amino Acid Activation in Protein Synthesis

• (f) Binding to Proteins 

• Some proteins bind to ATP in a characteristic protein fold, called as Rossmann fold. It is a general nucleotide binding structural domain that can also bind the coenzyme NAD. The most common ATP-binding proteins, known as kinases, share a small number of common folds. All protein kinases share common structural features specialized for ATP binding and phosphate transfer Aminoacyl-t RNA synthetase enzymes utilize ATP as an energy source to attach a tRNA molecule to its specific amino acid, forming an aminoacyl-t RNA complex, ready for translation at ribosomes. Required energy is made available from hydrolysis of ATP to AMP by removal of two phosphate groups. Amino acid activation refers to attachment of an amino acid its transfer RNA (TRNA). Aminoacyl transferase binds ATP to amino acid. In the process two phosphate groups are released. Aminoacyl transferase binds AMP-amino acid to tRNA. AMP is used in this step .

Creatinine Phosphate 

• Phosphate salt of creatinine is present in muscle. It is broken down to creatinine at a fairly constant rate depending on muscle mass of the body. Serum creatinine is an important indicator of renal health. It is a byproduct of muscle metabolism and is excreted unchanged by the kidney. It is produced via a biological system involving creatine, creatine phosphate (also known as phosphorcreatine) and adenosine triphosphate (ATP).

• Creatinine phosphate is formed from three amino acids: arginine (Arg), glycine (Gly) and methionine (Met). It is synthesized by formation of guanidinoacetate from Arg and Gly in kidney followed by methylation to creatinine in liver with the help of S-adenosyl methionine. It is further phosphorylated by creatinine kinase in presence of ATP to creatinine phosphate in muscle. Thus, it is synthesized in liver and transported to muscle cells for storage via blood stream.

• Each day, 1-2% of muscle creatine is converted to creatinine. Men tend to have higher levels of creatinine than women because of higher skeletal mass. Increased dietary intake of creatine or consuming more protein can increase daily creatinine excretion.

Basal Metabolic Rate (BMR)

• Basal metabolic rate (BMR) is the minimal rate of expenditure per unit time by endothermic animals at rest. It is reported in energy units/unit time ranging from watt (joule/second) to ml Oz/min or joule/hour/kg body mass J/(h.kg). While measuring BMR, the person should be in a physically and psychologically undisturbed state. The person should be in a thermally neutral environment, post-absorptive state and performing minimal metabolic activity. Thermally neutral environment means external temperature is fairly constant. Since, body temperature is constant at 37°C, any change in external temperature modifies metabolic rate. During digestion of food, metabolic activity increases. It remains fairly constant during post-absorptive state. The requirement of minimal meta.

• Metabolism comprises the processes which are needed by the body for normal functioning. BMR is the amount of energy expressed in calories which a person needs to keep the body functioning at rest. Some of the processes are breathing, blood circulation, controlling body temperature, cell growth, brain and nerve function and contraction of muscles. BMR affects the rate at which a person burns the calories. It may be with respect to constant weight, losing weight or gaining weight. BMR accounts for about 60-75% of daily calorie expenditure by individuals. It is influenced by several factors. It usually declines by 1-2% per decade after the age of 20. It is due to loss of fat free mass. There is lot of individual variability in this process.