HIGH - The language of Biochemistry - The language of ...

HIGH - The language of Biochemistry - The language of ...

HIGH ENERGY COMPOUDS ANJALI.H.S BCH.10.05.10 energy from the sun. phototrophic organisms &chemotrophic organisms.

both types of organisms share common mechanisms Once captured in chemical form, energy can be released in controlled exergonic reactions to drive a variety of life processes (which require energy). A small family of universal biomolecules mediates the flow of energy from exergonic reactions to the energy-requiring processes of life.

These molecules are the reduced coenzymes and the high-energy phosphate compounds. Phosphate compounds are considered high energy if they exhibit large negative free energies of hydrolysis (that is, if G is more negative than -25 kJ/mol). The exact amount of chemical free energy available from the hydrolysis of such compounds depends on concentration, pH, temperature, and so on But the G values for hydrolysis of these substances are substantially more

negative than for most other metabolic species. 1. high-energy phosphate compounds are not long-term energy storage substances. are transient forms of stored energy, meant to carry energy from point to point, from one enzyme system to another, in the minute-to-minute existence of the cell 2. the term HEC should not be construed to imply that these molecules are unstable and hydrolyze or decompose unpredictably.

Fritz Lipmann and high energy compounds Fritz Albert Lipmann (June 12, 1899 July 24, 1986) was a GermanAmerican biochemist and a co-discoverer in 1945 of coenzyme A. For this, together with other research on coenzyme A, he was awarded half the Nobel Prize in Physiology or Medicine in 1953 shared with Hans Adolf Krebs Lipmann went on the purpose that cells contain 2 classes of phosphorylated compounds and termed them as energy rich and energy poor giving considerations having low and negative free energies of hydrolysis

Lipmann described a sort of phosphate current in which photosynthesis or break down of food molecules generates energy rich phosphates that led to the synthesis of ATP power mechanical work. Compounds Free energy( kj/mol )

Phosphoenol pyruvate -62.2 cAMP -52.2

1,3-Bisphosphoglycerate -49.6 Creatine phosphate -43.3

Acetyl phosphate -43.3 ADP -35.7

ATP ,excess Mg 2+ -30.5 AMP -35.7

Pyrophosphate -33.6 AMP, excess Mg 2+ -32.6

Uridine diphosphoglucose -31.9 Acetyl CoA -31.5

Greater importance is the destabilizing effect of the electrostatic repulsions b/w the charged groups of a phosphoanhydride compared to that of its hydrolysis products. In physiological pH ATP has 3 or 4 ve charges whose mutual electrostatic repulsions are relieved by ATP hydrolysis. Smaller solvation energy of a phosphoanhydride compared to that of its hydrolysis products. Some estimates suggest that this factor provides the dominant thermodynamic .driving force for the hydrolysis of phosphoanhydride.

Why ATP? ATP holds an intermediate rank in HEP. ATP is uniquely situated between the very high energy phosphates synthesized in the breakdown of fuel molecules and the numerous lower-energy acceptor molecules that are phosphorylated in the course of further metabolic reactions. ADP can accept both phosphates and energy from the higher-energy phosphates, and the ATP thus formed can donate both phosphates and energy to the lowerenergy molecules of metabolism.

The ATP/ADP pair is an intermediately placed acceptor/donor system among highenergy phosphates. ATP Properties Molecular formula

Molar mass Density C10H16N5O13P3 507.18 g mol1 1.04 g/cm3 Melting point

187 C Acidity (pKa) 6.5 ATP was discovered in 1929 by Karl Lohmann

It was proposed to be the main energy-transfer molecule in the cell by Fritz Albert Lipmann in 1941. It was first artificially synthesized by Alexander Todd in 1948. ATP is considered to be the energy currency of life. It is the high-energy molecule that stores the energy

Often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism. Produced by photophosphorylation and cellular respiration and used by enzymes and structural proteins in many cellular processes, including biosynthetic reactions, motility, and cell division. One molecule of ATP contains three phosphate groups, and it is produced by ATP synthase from inorganic phosphate and adenosine diphosphate or adenosine monophosphate

The structure consists of a purine base Adenine attached to the 1' carbon atom of a pentose sugar -Ribose. Three phosphate groups are attached at the 5' carbon atom of the pentose sugar. It is the addition and removal of these phosphate groups that inter-convert ATP, ADP and AMP.

When ATP is used in DNA synthesis, the ribose sugar is first converted to deoxyribose by ribonucleotide reductase. Process of a phosphate group being added to ADP to become ATP is called photophosphoylation.

Synthase is the enzyme used in this process. ATP synthase makes ATP, which is the fuel for all the other molecular machines. ATP (adenosine triphosphate) can be broken down into ADP(adenosine diphosphate) and phosphate to release energy. When there are many H+ ion one side of a cell membrane, they want to cross to the less crowded side. In the process they travel through ATP synthase, and turn it as they go.

This turns the enzyme proteins that are outside of the membrane. The energy gained by rotation turns ADP and phosphate back into ATP. So, ATP synthase takes advantage of protons crossing the membrane to return ADP into ATP fuel. ATP is unstable because it has 3 negatively charged phosphate groups linked together sequentially. The negative charges are constantly pushing away from each other.

phosphorylated intermediate-transfer of phosphate group to keep the delta G negative - keep using/losing free E to do work 1. ATP transfers a Phosphate (p) to Amino Acid (AA)

2. Another AA takes the place of P 3. Result: a polypeptide and free P for oxidative phosphorylation in the ATP

Cycle. Phosphoric-Carboxylic Anhydrides The mixed anhydrides of phosphoric and carboxylic acids, frequently called acyl phosphates, are also energy-rich. Two biologically important acyl phosphates are acetyl phosphate and 1,3bisphosphoglycerate.

Hydrolysis of these species yields acetate and 3-phosphoglycerate, respectively, in addition to inorganic phosphate. Once again, the large G values indicate that the reactants are destabilized relative to products. This arises from bond strain, which can be traced to the partial positive charges on the carbonyl carbon and phosphorus atoms of these structures.

The energy stored in the mixed anhydride bond (which is required to overcome the charge-charge repulsion) is released upon hydrolysis. Increased resonance possibilities in the products relative to the reactants also contribute to the large negative G values. The value of G depends on the pKa values of the starting anhydride and the product phosphoric and carboxylic acids, and of course also on the pH of the medium.

1,3-Bisphosphoglyceric acid is a 3-carbon organic molecule present in most living organisms. as a metabolic intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis. is a transitional stage between glycerate 3-phosphate and glyceraldehyde 3phosphate during the fixation/reduction of CO2. is also a precursor to 2,3-bisphosphoglycerate which in turn is a reaction

intermediate in the glycolytic pathway. 2,3-Bisphosphoglyceric acid The high-energy acyl phosphate bond of 1,3BPG is important in respiration as it assists in the formation of ATP. Phosphoglycerate kinase transfers a phosphate group from 1,3-bisphosphoglycerate.

Similar role in the Calvin cycle to ADP for form ATP and 3-phosphoglycerate. 1,3BPG in the Calvin cycle does not produce ATP but instead uses it. 20% of 1,3-BPG is not metabolized in glycolytic pathway, instead. The reduction of ATP in the erythrocytes- molecule called 2,3-bisphoshoglyceric acid .

2,3BPG is used as a mechanism to oversee the efficient release of oxygen from hemoglobin. Low oxygen levels trigger a rise in 1,3BPG levels which in turn raises the level of 2,3BPG which alters the efficiency of oxygen dissociation from hemoglobin. Lactobacilli are another group of bacteria that produce butyrate but because they also produce lactate they are said to exhibit heterolactate fermentation. Lactobacilli ferment glucose to fructose 1,6 bisphosphate

fructose 1,6 bisphosphate aldolase. phosphoketolase. ENOL PHOSPHATES The largest value of G phosphoenolpyruvate or PEP

Is an important intermediate in carbohydrate metabolism and Due to its large negative G, it is a potent phosphorylating agent. PEP is formed via dehydration of 2-phosphoglycerate by enolase during fermentation and glycolysis. PEP into pyruvate upon transfer of its phosphate to ADP by pyruvate kinase It has the high-energy phosphate bond found (-61.9 kJ/ mol ) and is involved in glycolysis and gluconeogenesis.

In plants, it is also involved in the biosynthesis of various aromatic compounds, and in carbon fixation; in bacteria, it is also used as the source of energy for the phosphotransferase system. In glycolysis Metabolism of PEP to pyruvate = generates 1 molecule of ATP via substrate-level phosphorylation by pyruvate kinase

In gluconeogenesis PEP is formed from the decarboxylation of oxaloacetate and hydrolysis of one GTP. Is a rate-limiting step in gluconeogenesis GTP + oxaloacetate GDP + phosphoenolpyruvate + CO2 by PEPCK In plants Used for the synthesis of chorismate through the shikimate pathway Chorismate may then be metabolized into the aromatic amino acids (phe, try and tyr) In C plants, PEP serves as an important substrate in carbon fixation.

PEP + CO2 oxaloacetate by PEP carboxylase PYROPHOSPHATE In chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates PPi are essential for normal cellular functioning in virtually all living organisms

Name of esters formed by the condensation of a phosphorylated biological compound with inorganic phosphate as for dimethylallyl pyrophosphate. This bond is also referred to as a high-energy phosphate bond. Formed by the hydrolysis of ATP into AMP in cells. ATP AMP + PPi , pyrophosphorolysis Some reactions of ATP yields AMP +PPi pyrophosphate cleavage

PPi 2Pi by inorganic phosphatase The PPi cleavage of ATP yields two high energy phosphoanhydride bonds PPi cleavage in the synthesis of an aminoacyl-tRNA AA +AMP P P P P P P Aminoacyl-adenylate Aminoacyl-tRNA P P

P P 2Pi tRNA AMP aa is adenylated by ATP A tRNA molecule displaces the AMP moiety to form an aminoacyl-tRNA The exergonic hydrolysis of PPi ( G= -19.2 kj/mol) drives the reaction. ACETYL CoA

Structure of Acetyl CoA The structure of Acetyl CoA consists of two parts. 1. Acetyl group 2. Coenzyme A Beta- mercaptoethylamine Pantothenic acid (not synthesized in man -- an essential nutrient) Phosphate

3', 5'-adenosine diphosphate STRUCTURE CoA -mercaptoethylamine bonded throgh an amide linkage to pantothenic acid then attached to a 3 phosphoadenosine moiety via a pyrophosphate bridge. Acetyl group is bonded as a thioester linkage to the sulfhydryl portion of - mercaptothylamine

The G0 for the hydrolysis of its thioester bond is -31.5kj/ mol. is more exergonic than that of other esters because it is less stabilized by resonance due to large atomic radius of S that reduces the electronic overlap b/w C and S compared to C and O.

That free energy can be used to drive metabolic rxns. In TCA ,cleavage of a thioester (succinyl CoA) releases sufficient free energy to synthesize GTP from GDP and Pi. Precursors of Acetyl CoA Acetyl CoA is at the center of lipid metabolism. It is produced from: Fatty acids Glucose (through pyruvate)

Amino acids Ketone bodies Function of CoA CoA is a commonly used carrier for activated acyl groups (acetyl, fatty acyl and others). The thioester bond which links the acyl group to CoA has a large negative standard free energy of hydrolysis = -7.5 kcal/mole. This qualifies it as a high energy bond,

Products of Acetyl CoA Metabolism It can be converted to fatty acids, which in turn give rise to: triglycerides phospholipids eicosanoids (e.g., prostaglandins) ketone bodies It is the precursor of cholesterol, which can be converted to:

steroid hormones bile acids Overview of Acetyl CoA Metabolism URIDINE

DIPHOSPHOGLUCOSE A coenzyme C15H24N2O17P2 that reversibly catalyzes the formation of glucose-1phosphate from the corresponding phosphate of galactose and that acts as a donor of glucose residues in the biosynthesis of glycogen UDP-glucose consists of the pyrophosphate group, the pentose sugar ribose, glucose, and the nucleobase uracil.

Uridine diphosphate glucose (uracil- diphosphate glucose, UDP-glucose) is a nucleotide sugar. Involved in glycosyltransferase reactions in metabolism. Used in nucleotide sugars metabolism as an activated form of glucose as a substrate for enzymes called glucosyltransferases Precursor of glycogen and can be converted into UDP-galactose and UDP-glucuronic acid,

which can then be used as substrates by the enzymes that make polysaccharides containing galactose and glucuronic acid. UDP-glucose can also be used as a precursor of sucrose lipopolysaccharides, and glycosphingolipids. S-ADENOSYL METHIONINE S- Adenosyl methionine (SAM, SAMe, SAM-e) is a common co-substrate involved in

methyl group transfers. first discovered in Italy by G. L. Cantoni in 1952 made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase most SAM is produced and consumed in the liver. methyl group (CH3) attached to the methionine sulfur atom in SAM is chemically reactive. This allows donation of this group to an acceptor substrate in transmethylation

reactions. The reactions that produce, consume, and regenerate SAM are called the SAM cycle 1.S-AH hydrolyzed to homocysteine and adenosine by S- adenosylhomocysteine hydrolase and the homocysteine recycled back to Met through transfer of a CH3 group from 5-methylTHF. This Met can then be

converted back to SAM, completing the cycle. 2. Another pathway converts homocysteine to glutathione 3.The resulting adenosylhomocysteine is hydrolyzed to homocysteine, which may be catabolized via a complex pathway to cysteine and succinyl-CoA.

methylation of bases in tRNA methylation of cytosine residues in DNA

methylation of norepinephrine to form epinephrine conversion of the glycerophospholipid phosphatidylethanolamine to phosphatidylcholine PHOSPHOGUANIDINEs Phosphocreatine

is formed from parts of three aas: Arg Gly, and Met. can be synthesized by formation of guanidinoacetate from Arg and Gly (in kidney) by methylation (SAM) to creatine (in liver), and phosphorylation by CK(ATP) to phosphocreatine (in muscle); catabolism: dehydration to form the cyclic Shiff base creatinine.

Phosphocreatine is synthesized in the liver and transported to the muscle cells, via the bloodstream, for storage. Creatine phosphate shuttle facilitates transport of high energy phosphate from mitochondria Phosphocreatine can anaerobically donate a phosphate group to ADP to form ATP during the first 2 to 7 seconds following an intense muscular or neuronal effort. On the converse, excess ATP can be used during a period of low effort to convert

creatine to phosphocreatine. is catalyzed by several creatine kinases. The presence of creatine kinase (CK-MB, MB for muscle/brain) in plasma is indicative of tissue damage and is used in the diagnosis of myocardial infarction. The cell's ability to generate phosphocreatine from excess ATP during rest, as well as its use of phosphocreatine for quick regeneration of ATP Phosphocreatine plays a particularly important role in tissues that have high, fluctuating energy demands such as muscle and brain.

Difficult absorbing phosphocreatine, common creatine supplement is in the form of creatine monohydrate Body can readily produce the necessary phosphocreatine once the creatine has been ingested in the liver, pancreas and kidneys Require phosphocreatine to assist in the ATP cycle When phosphocreatine in the muscle breaks down, it is not reprocessed into a working form.

Phosphocreatine metabolizes into a substance known as creatinine, which is excreted through the kidneys and passed as urine. The level of creatinine in the blood is a useful indicator in the determination of kidney function

High levels of creatinine are a symptom of an inability of the kidney to filter the creatinine wastes. ATP + creatine phosphocreatine + ADP G = +12.6 kj/mol This reaction is endergonic under std cndtns ,however the intracellular conc of rctnts and pdts are such that it operates close to equilibrium In resting state [ATP] is relatively high , reaction proceeds forward but when [ATP] is low the reaction proceeds backward.

Thus PC act as an ATP buffer in cells that contains CK In invertebrates such as lobsters pa performs the same function These PGs are collectively named phosphagens PHOSPHOARGININE Three enzymatic systems and their substrates have been found to be functional for the synthesis of phosphoarginine and phosphocreatine from ATP. They are:

phosphoglycerate kinase, pyruvate kinase and oxidative phosphorylation in association with arginine kinase and creatine kinase respectively Arginine in invertebrates and creatine in vertebrates, by accepting phosphate, permit resting muscle after exercise to remove inorganic phosphate to rate-limiting levels in order to control glycogenolysis and glycolysis. The contraction-relaxation cycle causes the phosphate stored as phosphoarginine or phosphocreatine to flow back to reform a metabolic pool of inorganic phosphate.

The energy supply for eukaryotic ciliary and flagellar movement is thought to be maintained by ATP regenerating enzymes such as adenylate kinase, creatine kinase and arginine kinase. The energy supplying system for the ciliary movement of Paramecium caudatum was examined. Arginine kinase and adenylate kinase activities were detected in the cilia. Addition of PA increased the ciliary beat frequency

PA supplies energy as a phosphagen for ciliary beating in Paramecium caudatum, suggesting that PA functions not only as a reservoir of energy but also as a transporter of energy in these continuously energy-consuming circumstances. BIBLIOGRAPHY

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