High Energy compounds

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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
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.
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 lower-energy
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 mol−1
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 C₄ 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 ↔ 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.
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 →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
• 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 ∆G⁰ = +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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