HIGH ENERGY COMPOUDS ANJALI.H.S

1. HIGH ENERGY COMPOUDS ANJALI.H.S BCH.10.05.10

2. 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).

3. 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).

4. 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.

6. Fritz Lipmann and high energy compounds • Fritz Albert Lipmann (June 12, 1899 – July 24, 1986) was a German-American 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.

10. Greater importance is the destabilizing effect of the electrostatic repulsions b/w the charged groups of a phosphoanhydridecompared 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.

11. 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 lower-energy molecules of metabolism. • The ATP/ADP pair is an intermediately placed acceptor/donor system among high- energy phosphates.

12. ATP

14. 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.

15. 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

16. 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.

17. Process of a phosphate group being added to ADP to become ATP is called photophosphoylation. • Synthase is the enzyme used in this process.

18. 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. .

20. 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

22. Phosphoric-Carboxylic Anhydrides

23. 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 1,3-bisphosphoglycerate. • Hydrolysis of these species yields acetate and 3-phosphoglycerate, respectively, in addition to inorganic phosphate.

25. 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.

26. 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 3-phosphate 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

27. 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.

28. 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.

29. 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.

31. ENOL PHOSPHATES

32. 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

33. 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.

34. 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 C₄ plants, PEP serves as an important substrate in carbon fixation. PEP + CO2 → oxaloacetate by PEP carboxylase

35. PYROPHOSPHATE

36. 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

37. 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 ↔ Aminoacyl-adenylate ↔ Aminoacyl-tRNA ↓ 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.

38. ACETYL CoA

39. 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

41. CoA →β-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 β- mercaptothylamine structure

42. 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.

43. 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,

44. 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

45. Overview of Acetyl CoA Metabolism

46. URIDINE DIPHOSPHOGLUCOSE

47. A coenzyme C15H24N2O17P2that reversibly catalyzes the formation of glucose-1-phosphate 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.

48. 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.

49. S-ADENOSYL METHIONINE

50. 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.