Monday, March 2, 2015

Cellular respiration oxidizes food molecules,Glucose Catabolism,Glycolysis, Oxidation of Pyruvate,The Krebs Cycle,Harvesting Energy by Extracting Electrons,Electron Transport Chain,Aerobic Respiration,Mechanism of Muscle Contraction

Today we will see that how cell harvest Energy and how that Energy is utilized by our body to synthesize Protein,Muscles and power Locomotion in our body.
First Let's Start from Today's Topic
Cells harvest the energy in chemical bonds.
Using Chemical Energy to Drive Metabolism. The energy in C—H, C—O, and other chemical bonds can be captured and used to fuel the synthesis of ATP. Cellular respiration oxidizes food molecules.
An Overview of Glucose Catabolism. The chemical energy in sugar is harvested by both substrate-level phosphorylation and by aerobic respiration.
Stage One: Glycolysis. The 10 reactions of glycolysis capture energy from glucose by reshuffling the bonds.
Stage Two: The Oxidation of Pyruvate. Pyruvate, the product of glycolysis, is oxidized to acetyl-CoA.
Stage Three: The Krebs Cycle. In a series of reactions, electrons are stripped from acetyl-CoA.
Harvesting Energy by Extracting Electrons. The respiration of glucose is a series of oxidation-reduction reactions which involve stripping electrons from glucose and using the energy of these electrons to power the synthesis of ATP.
Stage Four: The Electron Transport Chain. The electrons harvested from glucose pass through a chain of membrane proteins that use the energy to pump protons, driving the synthesis of ATP.
Summarizing Aerobic Respiration. The oxidation of glucose by aerobic respiration in eukaryotes produces up to three dozen ATP molecules, over half the energy in the chemical bonds of glucose. Regulating Aerobic Respiration. High levels of ATP tend to shut down cellular respiration by feedback-inhibiting key reactions.
Catabolism of proteins and fats can yield considerable energy.
Glucose Is Not the Only Source of Energy. Proteins and fats are dismantled and the products fed into cellular respiration.
Cells can metabolize food without oxygen.
Fermentation. Fermentation allows continued metabolism in the absence of oxygen by donating the electrons harvested in glycolysis to organic molecules. Most foods contain a variety of carbohydrates, proteins, and fats, all rich in energy-laden chemical
bonds. Carbohydrates and fats, for example, possess many carbon-hydrogen (C—H), as well as carbon-oxygen (C—O) bonds. The job of extracting energy from this complex organic mixture is tackled in stages. First, enzymes break the large molecules down into smaller ones, a process called digestion. Then, other enzymes dismantle these fragments a little at a time, harvesting energy from C—H and other chemical bonds at each stage. This process is called catabolism.While you obtain energy from many of the constituents of food, it is traditional to focus first on the catabolism of carbohydrates. We will follow the six-carbon sugar, glucose (C6H12O6), as its chemical bonds are progressively harvested for energy. Later, we will come back and examine the catabolism of proteins and fats.
Cellular Respiration.
The energy in a chemical bond can be visualized as potential energy borne by the electrons that make up the covalent bond. Cells harvest this energy by putting the electrons to work, often to produce ATP, the energy currency of the cell. Afterward, the energy-depleted electron (associated with a proton as a hydrogen atom) is donated to some other molecule. When oxygen gas (O2) accepts the hydrogen atom, water forms, and the process is called aerobic respiration. When an inorganic molecule other than oxygen accepts the hydrogen, the process is called anaerobic respiration. When an organic molecule accepts the hydrogen atom, the process is called fermentation. Chemically, there is little difference between the catabolism of carbohydrates in a cell and the burning of wood in a fireplace. In both instances, the reactants are carbohydrates and oxygen, and the products are carbon dioxide, water, and energy:
C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + energy (heat or ATP).The change in free energy in this reaction is –720 kilocalories (–3012 kilojoules) per mole of glucose under the conditions found within a cell (the traditional value of –686 kilocalories, or –2870 kJ, per mole refers to standard conditions—room temperature, one atmosphere of pressure, etc.). This change in free energy results largely from the breaking of the six C—H bonds in the glucose molecule. The negative sign indicates that the products possess less free energy than the reactants. The same amount of energy is released whether glucose is catabolized or burned, but when it is burned most of the energy is released as heat. This heat cannot be used to perform work in cells. The key to a cell’s ability to harvest useful energy from the catabolism of food molecules such as glucose is its conversion of a portion of the energy into a more useful form. Cells do this by using some of the energy to drive the production of ATP, a molecule that can power cellular activities.
The ATP Molecule:
Adenosine triphosphate (ATP) is the energy currency of the cell, the molecule that transfers the energy captured during respiration to the many sites that use energy in the cell. How is ATP able to transfer energy so readily?  ATP is composed of a sugar (ribose) bound to an organic base (adenine) and a chain of three
phosphate groups. As shown here
Structure of the ATP molecule. ATP is composed of an organic base and a chain of phosphates attached to opposite ends of a five carbon sugar. Notice that the charged regions of the phosphate chain are close to one another. These like charges tend to repel one another, giving the bonds that hold them together a particularly high energy transfer potential.  each phosphate group is negatively charged. Because like charges repel each other, the linked phosphate groups push against the bond that holds them together. Like a cocked mousetrap, the linked phosphates store the energy of their electrostatic repulsion. Transferring a phosphate group to another molecule relaxes the electrostatic spring of ATP, at the same time cocking the spring of the molecule that is phosphorylated. This molecule can then use the energy to undergo some change that requires work.
How Cells Use ATP:
Cells use ATP to do most of those activities that require work. One of the most obvious is movement. Some bacteria swim about, propelling themselves through the water by rapidly spinning a long, tail-like flagellum, much as a ship moves by spinning a propeller. During your development as an embryo, many of your cells moved about, crawling over one another to reach new positions. Movement also occurs within cells. Tiny fibers within muscle cells pull against one another when muscles contract. Mitochondria pass a meter or more along the narrow nerve cells that connect your feet with your spine. Chromosomes are pulled by microtubules during cell division. All of these movements by cells require the expenditure of ATP energy.
A second major way cells use ATP is to drive endergonic reactions. Many of the synthetic activities of the cell are endergonic, because building molecules takes energy. The chemical bonds of the products of these reactions contain more energy, or are more organized, than the reactants. The reaction can’t proceed until that extra energy is supplied to the reaction. It is ATP that provides this needed energy.How ATP Drives Endergonic Reactions.How does ATP drive an endergonic reaction? The enzyme that catalyzes the endergonic reaction has two binding sites on its surface, one for the reactant and another for ATP. The ATP site splits the ATP molecule, liberating over 7 kcal (30 kJ) of chemical energy. This energy pushes the reactant at the second site “uphill,” driving the endergonic reaction. (In a similar way, you can make water in a swimming pool leap straight up in the air, despite the fact that gravity prevents water from rising spontaneously— just jump in the pool! The energy you add going in more than compensates for the force of gravity holding the water back.).
How ATP drives an endergonic reaction. In many cases, a phosphate group split from ATP activates a protein, catalyzing an endergonic process.
When the splitting of ATP molecules drives an energy requiring reaction in a cell, the two parts of the reaction— ATP-splitting and endergonic—take place in concert. In some cases, the two parts both occur on the surface of the same enzyme; they are physically linked, or “coupled,” like two legs walking. In other cases, a high-energy phosphate from ATP attaches to the protein catalyzing the endergonic process, activating it as shown above.Coupling energy requiring reactions to the splitting of ATP in this way is
one of the key tools cells use to manage energy. The catabolism of glucose into carbon dioxide and water in living organisms releases about 720 kcal (3012 kJ) of energy per mole of glucose. This energy is captured in ATP, which stores the energy by linking charged phosphate groups near one another. When the phosphate bonds in ATP are hydrolyzed, energy is released and available to do work.

Another are where we see utilization of ATP is in Mechanism of Muscle Contraction. Before looking into the Mechanism of muscle contraction let's know something about muscles.
MUSCLE:  Muscle is a specialised tissue of mesodermal origin. About 40-50 per cent of the body weight of a human adult is contributed by muscles. They have special properties like excitability, contractility, extensibility and elasticity. Muscles have been classified using different criteria, namely location, appearance and nature of regulation of their activities. Based on their location, three types of muscles are identified : (i) Skeletal (ii) Visceral and (iii) Cardiac. Skeletal muscles are closely associated with the skeletal components of the body. They have a striped appearance under the microscope and hence are called striated muscles. As their activities are under the voluntary control of the nervous system, they are known as voluntary muscles too. They are primarily involved in locomotory actions and changes of body postures. Visceral muscles are located in the inner walls of hollow visceral organs of the body like the alimentary canal, reproductive tract, etc. They do not exhibit any striation and are smooth in appearance. Hence, they are called smooth muscles (nonstriated muscle). Their activities are not under the voluntary control of the nervous system and are therefore known as involuntary muscles. They assist, for example, in the transportation of food through the digestive tract and gametes through the genital tract.As the name suggests, Cardiac muscles are the muscles of heart. Many cardiac muscle cells assemble in a branching pattern to form a cardiac muscle. Based on appearance, cardiac muscles are striated. They are involuntary in nature as the nervous system does not control their activities directly.
Let us examine a skeletal muscle in detail to understand the structure and mechanism of contraction. Each organised skeletal muscle in our body is made of a number of muscle bundles or fascicles held together by a common collagenous connective tissue layer called fascia. Each muscle bundle contains a number of muscle fibres
Diagrammatic cross sectional view of a muscle showing muscle bundles and muscle fibres. Each muscle fibre is lined by the plasma membrane called sarcolemma enclosing the sarcoplasm. Muscle fibre is a syncitium as the sarcoplasm contains many nuclei. The endoplasmic reticulum, i.e., sarcoplasmic reticulum of the muscle fibres is the store house of calcium ions. A characteristic feature of the muscle fibre is the presence of a large number of parallelly arranged filaments in the sarcoplasm called myofilaments or myofibrils. Each myofibril has alternate dark and light bands on it. A detailed study of the myofibril has established that the striated appearance is due to the distribution pattern of two important proteins – Actin and Myosin. The light bands contain actin and is called I-band or Isotropic band, whereas the dark band called ‘A’ or Anisotropic band contains myosin. Both the proteins are arranged as rod-like structures, parallel to each other and also to the longitudinal axis of the myofibrils. Actin filaments are thinner as compared to the myosin filaments, hence are commonly called thin and thick filaments respectively. In the centre of each ‘I’ band is an elastic fibre called ‘Z’ line which bisects it. The thin filaments are firmly attached to the ‘Z’ line. The thick filaments in the ‘A’ band are also held together in the middle of this band by a thin fibrous membrane called ‘M’ line. The ‘A’ and ‘I’ bands are arranged alternately throughout the length of the myofibrils. The portion of the myofibril between two successive ‘Z’ lines is considered as the functional unit of contraction and is called a sarcomere  as shown below
Diagrammatic representation of (a) anatomy of a muscle fibre showing a sarcomere (b) a sarcomere
In a resting state, the edges of thin filaments on either side of the thick filaments partially overlap the free ends of the thick filaments leaving the central part of the thick filaments. This central part of thick filament, not overlapped by thin filaments is called the ‘H’zone.
Structure of Contractile Proteins:
Each actin (thin) filament is made of two ‘F’ (filamentous) actins helically wound to each other. Each ‘F’ actin is a polymer of monomeric ‘G’ (Globular) actins. Two filaments of another protein, tropomyosin also run close to the ‘F’ actins throughout its length. A complex protein Troponin is distributed at regular intervals on the tropomyosin. In the resting state a subunit of troponin masks the active binding sites for myosin on the actin filaments
Each myosin (thick) filament is also a polymerised protein. Many monomeric proteins called Meromyosins
constitute one thick filament. Each meromyosin has two important parts, a globular head with a short arm and a tail, the former being called the heavy meromyosin (HMM) and the latter, the light meromyosin (LMM). The HMM component, i.e.; the head and short arm projects outwards at regular distance and angle from each other from the surface of a polymerised myosin filament and is known as cross arm. The globular head is an active ATPase enzyme and has binding sites for ATP and active sites for actin.
Mechanism of Muscle Contraction and Role of ATP:
Mechanism of muscle contraction is best explained by the sliding filament theory which states that contraction of a muscle fibre takes place by the sliding of the thin filaments over the thick filaments.
Muscle contraction is initiated by a signal sent by the central nervous system (CNS) via a motor neuron. A motor neuron alongwith the muscle fibres connected to it constitute a motor unit. The junction between a motor neuron and the sarcolemma of the muscle fibre is called the neuromuscular junction or motor-end plate. A neural signal reaching this junction releases a neurotransmitter (Acetyl choline) which generates an action potential in the sarcolemma. This spreads through the muscle fibre and causes the release of calcium ions into the sarcoplasm. Increase in Ca++ level leads to the binding of calcium with a subunit of troponin on actin filaments and thereby remove the masking of active sites for myosin.Utilising the energy from ATP hydrolysis, the myosin head now binds to the exposed active sites on actin to form a cross bridge
This pulls the attached actin filaments towards the centre of ‘A’ band. The ‘Z’ line attached to these actins are also pulled inwards thereby causing a shortening of the sarcomere, i.e., contraction. It is clear from the above steps, that during shortening of the muscle, i.e., contraction, the ‘I’ bands get reduced, whereas the ‘A’ bands retain the length .The myosin, releasing the ADP and P1 goes back to its relaxed state. A new ATP binds and the cross-bridge is broken .The ATP is again hydrolysed by the myosin head and the cycle of cross bridge formation and breakage is repeated causing further sliding. The process continues till the Ca++ ions are pumped back to the sarcoplasmic cisternae resulting in the masking of actin filaments. This causes the return of ‘Z’ lines back to their original position, i.e., relaxation. The reaction time of the fibres can vary in different muscles. Repeated activation of the muscles can lead to the accumulation of lactic acid due to anaerobic breakdown of glycogen in them, causing fatigue. Muscle contains a red coloured oxygen storing pigment called myoglobin. Myoglobin content is high in some of the muscles which gives a reddish appearance. Such muscles are called the Red fibres. These muscles also contain plenty of mitochondria which can utilise the large amount of oxygen stored in them for ATP production. These muscles, therefore, can also be called aerobic muscles. On the other hand, some of the muscles possess very less quantity of myoglobin and therefore, appear pale or whitish. These are the White fibres. Number of mitochondria are also few in them, but the amount of sarcoplasmic reticulum is high. They depend on anaerobic process for energy.
This is the role of hydrolysis of ATP to carry out non Spontaneous reaction. Cellular respiration oxidizes food molecules And hence Carry out all non spontaneous chemical reaction for which Del(G)>0.
An Overview of Glucose Catabolism
Cells are able to make ATP from the catabolism of organic molecules in two different ways. 1. Substrate-level phosphorylation. In the first, called substrate- level phosphorylation,
ATP is formed by transferring a phosphate group directly to ADP from a phosphate-bearing intermediate

During glycolysis, discussed below, the chemical bonds of glucose are shifted around in reactions that provide the energy required to form ATP.
Aerobic respiration. In the second, called aerobic respiration, ATP forms as electrons are harvested, transferred along the electron transport chain, and eventually donated to oxygen gas. Eukaryotes
produce the majority of their ATP from glucose in this way.

Glycolysis:
Stage One: Glycolysis. The first stage of extracting energy from glucose is a 10-reaction biochemical pathway called glycolysis that produces ATP by substrate-level phosphorylation. The enzymes that catalyze the glycolytic reactions are in the cytoplasm of the cell, not bound to any membrane or organelle. Two ATP molecules are used up early in the pathway, and four ATP molecules are formed by substrate-level phosphorylation. This yields a net of two ATP molecules for each molecule of glucose catabolized. In addition, four electrons are harvested as NADH that can be used to form ATP by aerobic respiration. Still, the total yield of ATP is small. When the glycolytic process is completed, the two molecules of pyruvate that are formed still contain most of the energy the original glucose molecule held.

Aerobic Respiration
Stage Two: Pyruvate Oxidation. In the second stage, pyruvate, the end product from glycolysis, is converted into carbon dioxide and a two-carbon molecule called acetyl- CoA. For each molecule of pyruvate converted, one molecule of NAD+ is reduced to NADH.
Stage Three: The Krebs Cycle. The third stage introduces this acetyl-CoA into a cycle of nine reactions called the Krebs cycle, named after the British biochemist, Sir Hans Krebs, who discovered it. (The Krebs cycle is also called the citric acid cycle, for the citric acid, or citrate, formed in its first step, and less commonly, the tricarboxylic acid cycle, because citrate has three carboxyl
groups.) In the Krebs cycle, two more ATP molecules are extracted by substrate-level phosphorylation, and a large number of electrons are removed by the reduction of NAD+ to NADH.
Stage Four: Electron Transport Chain. In the fourth stage, the energetic electrons carried by NADH are employed to drive the synthesis of a large amount of ATP by the electron transport chain. Pyruvate oxidation, the reactions of the Krebs cycle, and
ATP production by electron transport chains occur within many forms of bacteria and inside the mitochondria of all eukaryotes. The mitochondria are thought to have evolved from bacteria. Although plants and algae can produce ATP by photosynthesis, they also produce.ATP by aerobic respiration, just as animals and other nonphotosynthetic eukaryotes do.Below Figure  provides an overview of aerobic respiration.
An overview of aerobic respiration.

Anaerobic Respiration
In the presence of oxygen, cells can respire aerobically, using oxygen to accept the electrons harvested from food molecules. In the absence of oxygen to accept the electrons, some organisms can still respire anaerobically, using inorganic molecules to accept the electrons. For example, many bacteria use sulfur, nitrate, or other inorganic compounds as the electron acceptor in place of oxygen.
Methanogens. Among the heterotrophs that practice anaerobic respiration are primitive archaebacteria such as the thermophiles. Some of these, called methanogens, use CO2 as the electron acceptor, reducingCO2 to CH4 (methane) with the hydrogens derived from organic molecules produced by other organisms.

In aerobic respiration, the cell harvests energy from glucose molecules in a sequence of four major pathways: glycolysis, pyruvate oxidation, the Krebs cycle, and the electron transport chain. Oxygen is the final electron acceptor. Anaerobic respiration donates the harvested electrons to other inorganic compounds.

Stage One: Glycolysis
The metabolism of primitive organisms focused on glucose. Glucose molecules can be dismantled in many ways, but primitive organisms evolved a glucose-catabolizing process that releases enough free energy to drive the synthesis of ATP in coupled reactions. This process, called glycolysis, occurs in the cytoplasm and involves a sequence of 10 reactions that convert glucose into 2 three carbon molecules of pyruvate.How glycolysis works.
 For each molecule of glucose that passes through this transformation, the cell nets two ATP molecules by substrate-level phosphorylation.

Priming The first half of glycolysis consists of five sequential reactions that convert one molecule of glucose into two molecules of the three-carbon compound, glyceraldehyde 3- phosphate (G3P). These reactions demand the expenditure of ATP, so they are an energy-requiring process. Step A: Glucose priming. Three reactions “prime” glucose by changing it into a compound that can be cleaved readily into 2 three-carbon phosphorylated molecules. Two of these reactions require the cleavage of ATP, so this step requires the cell to use two ATP molecules. Step B: Cleavage and rearrangement. In the first of the remaining pair of reactions, the six-carbon product of step A is split into 2 three-carbon molecules. One is G3P, and the other is then converted to G3P by the second reaction
The glycolytic pathway. The first five reactions convert a molecule of glucose into two molecules of G3P. The second five reactions convert G3P into pyruvate.

Substrate-Level Phosphorylation in next paper.


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