CITRIC ACID CYCLE

Also known as the TCA cycle or Krebs cycle

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 is a series of chemical reactions used

by all aerobic organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and proteins into carbon dioxide. a series of enzyme-catalyzed chemical reactions that form a key part of aerobic respiration in cells

In addition,
the cycle provides precursors including

certain amino acids as well as the reducing agent NADH that is used in numerous biochemical reactions Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically.

Origin of the cycles name

The name of this metabolic pathway is

derived from citric acid (a type of tricarboxylic acid) that is first consumed and then regenerated by this sequence of reactions to complete the cycle.

Evolution
Components of the TCA cycle were derived

from anaerobic bacteria, and the TCA cycle itself may have evolved more than once. Theoretically there are several alternatives to the TCA cycle, however the TCA cycle appears to be the most efficient. If several TCA alternatives had independently evolved, they all appear to have converged onto the canonical TCA cycle.

Definition of terms
Pyruvate-

Pyruvate is the end product of glycolysis, which is converted into acetyl coA that enters the Krebs cycle when there is sufficient oxygen available. When the oxygen is insufficient, pyruvate is broken down anaerobically, creating lactate in animals (including humans) and ethanol in plants.

Definition of terms
Acetyl-CoA

Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.

Definition of terms
FAD - flavin adenine dinucleotide (FAD) In biochemistry, is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety (vitamin B2) bound to the phosphate group of an ADP molecule FAD can be reduced to FADH2, whereby it accepts two hydrogen atoms (a net gain of two electrons):

Definition of terms
NADH - Nicotinamide adenine dinucleotide, - abbreviated NAD+, is a coenzyme found in all living cells. - In metabolism, NAD+ is involved in redox reactions, carrying electrons from one reaction to another. - The coenzyme is, therefore, found in two forms in cells: NAD+ is an oxidizing agent it accepts electrons from other molecules and becomes reduced. This reaction forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD+.

The cycle overview

a two carbon organic product acetate in the form of acetylCoA is produced through catabolism of sugars, fats, and proteins. 2. Acetyl-CoA along with two equivalents of water (H2O) is consumed by the citric acid cycle producing two equivalents of carbon dioxide (CO2) and one equivalent of HS-CoA. 3. one complete turn of the cycle converts three equivalents of nicotinamide adenine dinucleotide (NAD+) into three equivalents of reduced NAD+ (NADH), one equivalent of ubiquinone (Q) into one equivalent of reduced ubiquinone (QH2), and one equivalent each of guanosine diphosphate (GDP) and inorganic phosphate (Pi) into one equivalent of guanosine triphosphate (GTP). 4. The NADH and QH2 generated by the citric acid cycle are in turn used by the oxidative phosphorylation pathway to generate energy-rich adenosine triphosphate (ATP).
1.

 One of the primary sources of acetyl-CoA is sugars

that are broken down by glycolysis to produce pyruvate that in turn is decarboxylated by the enzyme pyruvate dehydrogenase generating acetyl-CoA according to the following reaction scheme:

CH3C(=O)C(=O)O (pyruvate) + HSCoA + NAD+ CH3C(=O)SCoA (acetyl-CoA) + NADH + CO2

The product of this reaction, acetyl-CoA, is the starting point for the citric acid cycle.

During glycolysis, glucose is broken down to pyruvate.

A two-carbon fragment of pyruvate is used to form acetyl-CoA. The acetyl CoA enters the Krebs Cycle, which occurs in the mitochondrion.

During the conversion of pyruvate to acetyl-CoA, carbon dioxide (CO2) is produced and a molecule of NADH is formed

The two carbon acetyl portion of the acetyl-CoA is transferred to a 4-carbon molecule, producing a six-carbon compound. The CoA carrier molecule is released.

Carbon dioxide is then released from the 6-carbon molecule, forming a 5carbon compound. In this step, hydrogen is removed and transferred to NAD+ to form NADH

Next, a second oxidation and decarboxylation occurs. Again, NADH and carbon diocide are produced. In addtition, a molecule of ATP is produced. As a result of these reactions, a 4-carbon molecule is formed in the Krebs Cycle.

Finally the 4-carbon molecule is further oxidized and the hydrogens that are removed are used to form NADH and FADH2. These reactions regenerate the 4-carbon molecule that initially reacts with acetyl-CoA.

Each glucose molecule is broken down into two pyruvate molecules during glycolysis. Then each pyruvate is converted to acetyl-CoA, which enters the Krebs Cycle.

Thus, for each glucose molecule, the Krebs cycle must complete two circuits to completely break dwon the two pyruvate molecules .

Simplified

2 only per cylce

 The greatly simplified cycle below starts with

pyruvate, which is the end product of gylcolysis, the first step of all types of cell respiration. Since it is well known that ATP is the energy currency that is used for nearly every task in the human body and other organisms, it may seem surprising that so little ATP is produced directly by the TCA cycle. But the TCA cycle as shown here represents the process taking place in the matrix of the mitochondria using the reactions with NAD+ and FAD which carry high energy electrons to the electron transport systemsin the inner mitochondrial membrane. The reactions there are responsible for the production of most of the ATP yield by chemiosmosis.

 The Krebs cycle, also called the citric acid

cycle, is a fundamental metabolic pathway involving eight enzymes essential for energy production through aerobic respiration, and, like glycolysis, arose early in evolution The Krebs cycle takes place in mitochondria where it oxidizes acetyl-CoA, releasing carbon dioxide and extracting energy primarily as the reduced high-energy electron carriers NADH and FADH2. NADH and FADH2 transfer chemical energy from metabolic intermediates to the electron transport chain to create a different form of energy, a gradient of protons across the inner mitochondrial membrane.

 The Krebs cycle, like other metabolic pathways,

is tightly regulated to efficiently meet the needs of the cell and the organis Some Krebs cycle enzymes require non-protein cofactors for activity, such as thiamine, vitamin B1. Insufficient quantities of this vitamin in the diet leads to decreased activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, and a decrease in the ability of the Krebs cycle to meet metabolic demands, causing the disease beriberi.

 Kreb's cycle is important in the processes

of cellular respiration as well as the processing of fats and other molecules for the harvesting of chemical energy Fats are broken down in a process called beta oxidation and enter the Kreb's cycle as acetyl groups.