A report on Cofactor (biochemistry) and Nicotinamide adenine dinucleotide

The succinate dehydrogenase complex showing several cofactors, including flavin, iron–sulfur centers, and heme.

The redox reactions of nicotinamide adenine dinucleotide.

A simple [Fe2S2] cluster containing two iron atoms and two sulfur atoms, coordinated by four protein cysteine residues.

Some metabolic pathways that synthesize and consume NAD in vertebrates. The abbreviations are defined in the text.

Salvage pathways use three precursors for NAD+.

Rossmann fold in part of the lactate dehydrogenase of Cryptosporidium parvum, showing NAD in red, beta sheets in yellow, and alpha helices in purple.

In this diagram, the hydride acceptor C4 carbon is shown at the top. When the nicotinamide ring lies in the plane of the page with the carboxy-amide to the right, as shown, the hydride donor lies either "above" or "below" the plane of the page. If "above" hydride transfer is class A, if "below" hydride transfer is class B.

A simplified outline of redox metabolism, showing how NAD and NADH link the citric acid cycle and oxidative phosphorylation.

Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism.

- Nicotinamide adenine dinucleotide

For example, the multienzyme complex pyruvate dehydrogenase at the junction of glycolysis and the citric acid cycle requires five organic cofactors and one metal ion: loosely bound thiamine pyrophosphate (TPP), covalently bound lipoamide and flavin adenine dinucleotide (FAD), cosubstrates nicotinamide adenine dinucleotide (NAD+) and coenzyme A (CoA), and a metal ion (Mg2+).

- Cofactor (biochemistry)

8 related topics with Alpha

Enzyme

3 links

Enzymes are proteins that act as biological catalysts (biocatalysts).

Enzyme activity initially increases with temperature (Q10 coefficient) until the enzyme's structure unfolds (denaturation), leading to an optimal rate of reaction at an intermediate temperature.

Organisation of enzyme structure and lysozyme example. Binding sites in blue, catalytic site in red and peptidoglycan substrate in black.

Enzyme changes shape by induced fit upon substrate binding to form enzyme-substrate complex. Hexokinase has a large induced fit motion that closes over the substrates adenosine triphosphate and xylose. Binding sites in blue, substrates in black and Mg2+ cofactor in yellow.

Chemical structure for thiamine pyrophosphate and protein structure of transketolase. Thiamine pyrophosphate cofactor in yellow and xylulose 5-phosphate substrate in black.

The energies of the stages of a chemical reaction. Uncatalysed (dashed line), substrates need a lot of activation energy to reach a transition state, which then decays into lower-energy products. When enzyme catalysed (solid line), the enzyme binds the substrates (ES), then stabilizes the transition state (ES‡) to reduce the activation energy required to produce products (EP) which are finally released.

The metabolic pathway of glycolysis releases energy by converting glucose to pyruvate via a series of intermediate metabolites. Each chemical modification (red box) is performed by a different enzyme.

In phenylalanine hydroxylase over 300 different mutations throughout the structure cause phenylketonuria. Phenylalanine substrate and tetrahydrobiopterin coenzyme in black, and Fe2+ cofactor in yellow.

Hereditary defects in enzymes are generally inherited in an autosomal fashion because there are more non-X chromosomes than X-chromosomes, and a recessive fashion because the enzymes from the unaffected genes are generally sufficient to prevent symptoms in carriers.

In some enzymes, no amino acids are directly involved in catalysis; instead, the enzyme contains sites to bind and orient catalytic cofactors.

the hydride ion (H−), carried by NAD or NADP+

Metabolism

3 links

Set of life-sustaining chemical reactions in organisms.

Structure of adenosine triphosphate (ATP), a central intermediate in energy metabolism

This is a diagram depicting a large set of human metabolic pathways.

Glucose can exist in both a straight-chain and ring form.

Structure of the coenzyme acetyl-CoA.The transferable acetyl group is bonded to the sulfur atom at the extreme left.

The structure of iron-containing hemoglobin. The protein subunits are in red and blue, and the iron-containing heme groups in green. From.

A simplified outline of the catabolism of proteins, carbohydrates and fats

Mechanism of ATP synthase. ATP is shown in red, ADP and phosphate in pink and the rotating stalk subunit in black.

Plant cells (bounded by purple walls) filled with chloroplasts (green), which are the site of photosynthesis

Simplified version of the steroid synthesis pathway with the intermediates isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP) and squalene shown. Some intermediates are omitted for clarity.

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1), which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).

Evolutionary tree showing the common ancestry of organisms from all three domains of life. Bacteria are colored blue, eukaryotes red, and archaea green. Relative positions of some of the phyla included are shown around the tree.

Metabolic network of the Arabidopsis thaliana citric acid cycle. Enzymes and metabolites are shown as red squares and the interactions between them as black lines.

Aristotle's metabolism as an open flow model

Santorio Santorio in his steelyard balance, from Ars de statica medicina, first published 1614

These group-transfer intermediates are called coenzymes.

Nicotinamide adenine dinucleotide (NAD+), a derivative of vitamin B3 (niacin), is an important coenzyme that acts as a hydrogen acceptor.

Glycolysis

2 links

Metabolic pathway that converts glucose , into pyruvic acid (CH3COCO2H).

Summary of the 10 reactions of the glycolysis pathway

Eduard Buchner. Discovered cell-free fermentation.

Otto Meyerhof. One of the main scientists involved in completing the puzzle of glycolysis

Bacillus stearothermophilus phosphofructokinase

The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH).

Arthur Harden and William Young along with Nick Sheppard determined, in a second experiment, that a heat-sensitive high-molecular-weight subcellular fraction (the enzymes) and a heat-insensitive low-molecular-weight cytoplasm fraction (ADP, ATP and NAD+ and other cofactors) are required together for fermentation to proceed.

Interactive animation of the structure of ATP

Adenosine triphosphate

2 links

Organic compound and hydrotrope that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis.

The cycles of synthesis and degradation of ATP; 2 and 1 represent input and output of energy, respectively.

This image shows a 360-degree rotation of a single, gas-phase magnesium-ATP chelate with a charge of −2. The anion was optimized at the UB3LYP/6-311++G(d,p) theoretical level and the atomic connectivity modified by the human optimizer to reflect the probable electronic structure.

An example of the Rossmann fold, a structural domain of a decarboxylase enzyme from the bacterium Staphylococcus epidermidis with a bound flavin mononucleotide cofactor.

It is also a precursor to DNA and RNA, and is used as a coenzyme.

Two equivalents of NADH are also produced, which can be oxidized via the electron transport chain and result in the generation of additional ATP by ATP synthase.

Nucleotide

1 links

Nucleotides are organic molecules consisting of a nucleoside and a phosphate.

Showing the arrangement of nucleotides within the structure of nucleic acids: At lower left, a monophosphate nucleotide; its nitrogenous base represents one side of a base-pair. At the upper right, four nucleotides form two base-pairs: thymine and adenine (connected by double hydrogen bonds) and guanine and cytosine (connected by triple hydrogen bonds). The individual nucleotide monomers are chain-joined at their sugar and phosphate molecules, forming two 'backbones' (a double helix) of nucleic acid, shown at upper left.

Structural elements of three nucleo tides —where one-, two- or three-phosphates are attached to the nucleo side (in yellow, blue, green) at center: 1st, the nucleotide termed as a nucleoside mono phosphate is formed by adding a phosphate (in red); 2nd, adding a second phosphate forms a nucleoside di phosphate; 3rd, adding a third phosphate results in a nucleoside tri phosphate. + The nitrogenous base (nucleobase) is indicated by "Base" and "glycosidic bond" (sugar bond). All five primary, or canonical, bases—the purines and pyrimidines—are sketched at right (in blue).

The synthesis of UMP. The color scheme is as follows: enzymes, <span style="color: rgb(219,155,36);">coenzymes, <span style="color: rgb(151,149,45);">substrate names , <span style="color: rgb(128,0,0);">inorganic molecules

The synthesis of IMP. The color scheme is as follows: enzymes, <span style="color: rgb(219,155,36);">coenzymes, <span style="color: rgb(151,149,45);">substrate names , <span style="color: rgb(227,13,196);">metal ions , <span style="color: rgb(128,0,0);">inorganic molecules

They provide chemical energy—in the form of the nucleoside triphosphates, adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP) and uridine triphosphate (UTP)—throughout the cell for the many cellular functions that demand energy, including: amino acid, protein and cell membrane synthesis, moving the cell and cell parts (both internally and intercellularly), cell division, etc. In addition, nucleotides participate in cell signaling (cyclic guanosine monophosphate or cGMP and cyclic adenosine monophosphate or cAMP), and are incorporated into important cofactors of enzymatic reactions (e.g. coenzyme A, FAD, FMN, NAD, and NADP+).

Sodium and fluorine bonding ionically to form sodium fluoride. Sodium loses its outer electron to give it a stable electron configuration, and this electron enters the fluorine atom exothermically. The oppositely charged ions are then attracted to each other. The sodium is oxidized; and the fluorine is reduced.

Redox

1 links

Type of chemical reaction in which the oxidation states of substrate change.

The international pictogram for oxidizing chemicals

A redox reaction is the force behind an electrochemical cell like the Galvanic cell pictured. The battery is made out of a zinc electrode in a ZnSO4 solution connected with a wire and a porous disk to a copper electrode in a CuSO4 solution.

Oxides, such as iron(III) oxide or rust, which consists of hydrated iron(III) oxides Fe2O3·nH2O and iron(III) oxide-hydroxide (FeO(OH), Fe(OH)3), form when oxygen combines with other elements

Enzymatic browning is an example of a redox reaction that takes place in most fruits and vegetables.

Blast furnaces of Třinec Iron and Steel Works, Czech Republic

The process of cell respiration also depends heavily on the reduction of NAD+ to NADH and the reverse reaction (the oxidation of NADH to NAD+).

In general, the electron donor is any of a wide variety of flavoenzymes and their coenzymes.

Pyruvate dehydrogenase

0 links

Enzyme that catalyzes the reaction of pyruvate and a lipoamide to give the acetylated dihydrolipoamide and carbon dioxide.

Simplified mechanism for pyruvate dehydrogenase reaction. The TPP coenzyme is shown with abbreviated substituents.

Pyruvate dehydrogenase E1 subunit of E. coli. Colors represent different chains. Structure determined by Arjunan et al. Biochemistry 2002. Created with PyMol.

The conversion requires the coenzyme thiamine pyrophosphate.

Phosphorylation is reversed by pyruvate dehydrogenase phosphatase, which is stimulated by insulin, PEP, and AMP, but competitively inhibited by ATP, NADH, and Acetyl-CoA.

A man with pellagra, which is caused by a chronic lack of vitamin B3 in the diet

Niacin

0 links

Organic compound and a form of vitamin B3, an essential human nutrient.

Niacin, serotonin (5-hydroxytryptamine), and melatonin biosynthesis from tryptophan

The amide derivative nicotinamide (niacinamide) is a component of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP+).

Niacin and nicotinamide are both converted into the coenzyme NAD.