Wednesday, October 22, 2008

Lecture 3 - Glycolysis, Kreb's and Electron Transport

Krebs Cycle

The citric acid cycle, also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle, (or rarely, the Szent-Györgyi-Krebs cycle) is a series of enzyme-catalysed chemical reactions of central importance in all living cells that use oxygen as part of cellular respiration. In eukaryotes, the citric acid cycle occurs in the matrix of the mitochondrion. The components and reactions of the citric acid cycle were established by seminal work from both Albert Szent-Györgyi and Hans Krebs.

In aerobic organisms, the citric acid cycle is part of a metabolic pathway involved in the chemical conversion of carbohydrates, fats and proteins into carbon dioxide and water to generate a form of usable energy. Other relevant reactions in the pathway include those in glycolysis and pyruvate oxidation before the citric acid cycle, and oxidative phosphorylation after it. In addition, it provides precursors for many compounds including some amino acids and is therefore functional even in cells performing fermentation.

Electron Transport Chain and Oxidative Phosphorylation

An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer of H+ ions across a membrane, through a set of mediating biochemical reactions. These H+ ions are used to produce adenosine triphosphate (ATP), the main energy intermediate in living organisms, as they move back across the membrane. Electron transport chains are used for extracting energy from sunlight (photosynthesis) and from redox reactions such as the burning of sugars (respiration).

Electron transport chains in mitochondria
The cells of almost all eukaryotes (animals, plants, fungi, algae, protozoa – in other words, the living things except bacteria, archaea, and a few protists) contain intracellular organelles called mitochondria, which produce ATP. Energy sources such as glucose are initially metabolized in the cytoplasm. The products are imported into mitochondria. Mitochondria continue the process of catabolism using metabolic pathways including the Krebs cycle, fatty acid oxidation, and amino acid oxidation.

The end result of these pathways is the production of two kinds of energy-rich electron donors, NADH and succinate. Electrons from these donors are passed through an electron transport chain to oxygen, which is reduced to water. This is a multi-step redox process that occurs on the mitochondrial inner membrane. The enzymes that catalyze these reactions have the remarkable ability to simultaneously create a proton gradient across the membrane, producing a thermodynamically unlikely high-energy state with the potential to do work. Although electron transport occurs with great efficiency, a small percentage of electrons are prematurely leaked to oxygen, resulting in the formation of the toxic free-radical superoxide.

The similarity between intracellular mitochondria and free-living bacteria is striking. The known structural, functional, and DNA similarities between mitochondria and bacteria provide strong evidence that mitochondria evolved from intracellular prokaryotic symbionts that took up residence in primitive eukaryotic cells.

Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate (ATP). Although the many forms of life on earth use a range of different nutrients, almost all carry out oxidative phosphorylation to produce ATP, the molecule that supplies energy to metabolism. This pathway is probably so pervasive because it is a highly efficient way of releasing energy, compared to alternative fermentation processes such as anaerobic glycolysis.

During oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors such as oxygen, in redox reactions. These redox reactions release energy, which is used to form ATP. In eukaryotes, these redox reactions are carried out by a series of protein complexes within mitochondria, whereas in prokaryotes, these proteins are located in the cells' inner membranes. These linked sets of enzymes are called electron transport chains. In eukaryotes, five main protein complexes are involved, whereas in prokaryotes many different enzymes are present, using a variety of electron donors and acceptors.

The energy released as electrons flow through this electron transport chain is used to transport protons across the inner mitochondrial membrane, in a process called chemiosmosis. This generates potential energy in the form of a pH gradient and an electrical potential across this membrane. This store of energy is tapped by allowing protons to flow back across the membrane and down this gradient, through a large enzyme called ATP synthase. This enzyme uses this energy to generate ATP from adenosine diphosphate (ADP), in a phosphorylation reaction. Unusually, the ATP synthase is driven by the proton flow which forces the rotation of a part of the enzyme—it is a rotary mechanical motor.

Although oxidative phosphorylation is a vital part of metabolism, it produces reactive oxygen species such as superoxide and hydrogen peroxide that lead to propagation of free radicals, damaging cells and contributing to disease and, possibly, aging. The enzymes carrying out this metabolic pathway are also the target of many drugs and poisons that inhibit their activities.

Adenosine-5'-triphosphate (ATP) is a multifunctional nucleotide that is most important as a "molecular currency" of intracellular energy transfer.[1] In this role, ATP transports chemical energy within cells for metabolism. It is produced as an energy source during the processes of photosynthesis and cellular respiration and consumed by many enzymes and a multitude of cellular processes including biosynthetic reactions, motility and cell division. In signal transduction pathways, ATP is used as a substrate by kinases that phosphorylate proteins and lipids, as well as by adenylate cyclase, which uses ATP to produce the second messenger molecule cyclic AMP.

ATP is generated in the cell by energy-consuming processes and is broken down by energy-releasing processes. In this way ATP transfers energy between spatially-separate metabolic reactions. ATP is the main energy source for the majority of cellular functions. This includes the synthesis of macromolecules, including DNA, RNA, and proteins. ATP also plays a critical role in the transport of macromolecules across cell membranes, e.g. exocytosis and endocytosis.

ATP is critically involved in maintaining cell structure by facilitating assembly and disassembly of elements of the cytoskeleton. In a related process, ATP is required for the shortening of actin and myosin filament crossbridges required for muscle contraction. This latter process is one of the main energy requirements of animals and is essential for locomotion and respiration.

The structure of this molecule 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. ATP is also incorporated into nucleic acids by polymerases in the processes of DNA replication and transcription.

ATP is commonly referred to as a "high energy molecule"; however by itself, this is incorrect. A mixture of ATP and ADP at equilibrium in water can do no useful work at all.[5] Similarly, ATP does not contain "high-energy bonds," rather the "high-energy bonds" are between its products and water, and the bonds within ATP are notable simply for being of lower energy than the new bonds produced when ATP reacts with water. Any other unstable system of potentially reactive molecules would serve as a way of storing energy, if the cell maintained their concentration far from the equilibrium point of the reaction.[5]

The amount of energy released from hydrolysis of ATP can be calculated from the changes in energy under non-natural conditions. The net change in heat energy (enthalpy) at standard temperature and pressure of the decomposition of ATP into hydrated ADP and hydrated inorganic phosphate is −20.5 kJ/mol, with a change in free energy of 3.4 kJ/mol.[6] The energy released by cleaving either a phosphate (Pi) or pyrophosphate (PPi) unit from ATP, with all reactants and products at their standard states of 1 M concentration, are:

ATP + H2O → ADP(hydrated) + Pi(hydrated) + H+(hydrated) ΔG˚ = -30.54 kJ/mol (−7.3 kcal/mol)

ATP + H2O → AMP(hydrated) + PPi(hydrated) + H+(hydrated) ΔG˚ = -45.6 kJ/mol (−10.9 kcal/mol)

These values can be used to calculate the change in energy under physiological conditions and the cellular ATP/ADP ratio. The values given for the Gibbs free energy for this reaction are dependent on a number of factors, including overall ionic strength and the presence of alkaline earth metal ions such as Mg2+ and Ca2+. Under typical cellular conditions, ΔG is approximately −57 kJ/mol (−14 kcal/mol).[7]

The overall process of oxidizing glucose to carbon dioxide is known as cellular respiration and can produce up to 36 molecules of ATP from a single molecule of glucose.[12] ATP can be produced by a number of distinct cellular processes; the three main pathways used to generate energy in eukaryotic organisms are glycolysis and the citric acid cycle/oxidative phosphorylation, both components of cellular respiration; and beta-oxidation. The majority of this ATP production by a non-photosynthetic aerobic eukaryote takes place in the mitochondria, which can make up nearly 25% of the total volume of a typical cell.

AS405 –Day 3 Homework Name: ____________________

1. Compare and Contrast chemiosmosis in mitochondria and chloroplasts.

2. Compare and Contrast prokaryotic and eukaryotic cells.

3. Compare and Contrast plant and animal cells.

4. Give examples of exocytosis and endocytosis.

5. Define diffusion, osmosis, and electrochemical gradient and give examples.

1 comment:

Jessi said...

Here is a website that explaisn chemiosmosis with pictures and little videos. Very helpful.