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NIACIN

BIOCHEMISTRY

mprasadnaidu
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NIACIN

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  1. NIACIN M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.

  2. Nicotinamide adenine dinucleotide  is a dinucleotide containing two nucleotides joined by phosphate groups, with one nucleotide containing an adenine base and the other containing nicotinamide. • electron transfer reactions are the main function of NAD+ • Also used in other cellular processes, the most notable one being a substrate of enzymes that add or remove chemical groups from proteins, in posttranslational modifications.

  3. Concentration and state in cells • more than 80% of mitochondrial NADH is bound to proteins. • NAD+/NADH ratio – is an important component of w redox state of a cell, which reflects both the metabolic activities and the health of cells. • Normal ratio is  0.05 to 4. •  NADP+/NADPH ratio is normally about 0.005. •  NADH in solution has an emission peak at 460 nm • while the oxidized form of the coenzyme does not fluoresce

  4. de novo Biosynthesis • NAD+ can be synthesized from simple building-blocks from the amino acids tryptophan or aspartic acid. •  generation of quinolinic acid (QA) from an amino acid—either tryptophan (Trp) in animals and some bacteria, or aspartic acid in some bacteria and plants. • The quinolinic acid is converted to nicotinic acid mononucleotide (NaMN) by transfer of a phosphoribose moiety. An adenylate moiety is then transferred to form nicotinic acid adenine dinucleotide (NaAD). Finally, the nicotinic acid moiety in NaAD is amidated to a nicotinamide (Nam) moiety, forming nicotinamide adenine dinucleotide.

  5. Salvage pathway • Three natural compounds containing the nicotinamide ring and used in these salvage metabolic pathways are nicotinic acid (Na), nicotinamide (Nam) and nicotinamideriboside (NR). • nicotinamide moiety is released from NAD+ in ADP-ribose transfer reactions • Despite the presence of the de novo pathway, the salvage reactions are essential in humans,a lack of niacin in the diet causes the vitamin deficiency disease pellagra.

  6. Functions • Oxidoreductases • The main role of NAD+ in metabolism is the transfer of electrons from one molecule to another. • Reactions of this type are catalyzed by a large group of enzymes called oxidoreductases.

  7. Role in redox metabolism • the redox reactions catalyzed by oxidoreductases are vital in all parts of metabolism, but one particularly important area where these reactions occur is in the release of energy from nutrients.

  8. Non-redox roles (MBBS) • In addition to is coenzyme role, NAD is the source of ADP-ribose. • ADP-ribose is used in posttranslational modification called ADP-ribosylation. • Mono-ADP-ribosylation was first identified as the mechanism of a group of bacterial toxins, notably cholera toxin, but it is also involved in normal cell signaling. • Poly ADP-ribosylationis involved in the regulation of several cellular events and is most important in the cell nucleus, in processes such as DNA repair and telomere maintenance.

  9. Cyclic ADP-ribose and nicotinic acid adenine dinucleotide, formed from NAD, act to increase intracellular calcium in response to neurotransmitters and hormones. • Extracellular calcium is maintained by Para thyroid hormone.

  10. Non-redox roles(PGs) • The coenzyme NAD+ is also consumed in ADP-ribose transfer reactions. •  ADP-ribosyltransferases add the ADP-ribose moiety of NAD to proteins, in posttranslational modification called ADP-ribosylation. • ADP-ribosylation involves either the addition of a single ADP-ribose moiety, in mono-ADP-ribosylation, or the transferral of ADP-ribose to proteins in long branched chains, which is called polyADP-ribosylation

  11. Another function of this coenzyme in cell signaling is as a precursor of cyclic ADP-ribose, which is produced from NAD+ by ADP-ribosylcyclases, as part of a second messenger system. • This molecule acts in calcium signaling by releasing calcium from intracellular stores.It does this by binding to and opening a class of calcium channels called ryanodine receptors, which are located in the membranes of organelles, such as the endoplasmic reticulum.

  12. Other NAD-dependent enzymes include bacterial DNA ligases, which join two DNA ends by using NAD+ as a substrate to donate an adenosine monophosphate (AMP) moiety to the 5' phosphate of one DNA end. This intermediate is then attacked by the 3' hydroxyl group of the other DNA end, forming a new phosphodiester bond

  13. Thank you

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