Glutathione (GSH) vs NAD+ (Nicotinamide Adenine Dinucleotide)

Glutathione (GSH)

Glutathione is a tripeptide of glutamate, cysteine and glycine in which glutamate is linked through its side-chain (gamma) carboxyl group. It is made inside cells by two ATP-dependent enzymes, glutamate–cysteine ligase and glutathione synthetase, and is one of the most abundant small thiols in animal cells. It occurs in a reduced form (GSH) and an oxidised disulfide form (GSSG), and the ratio between them is widely used as a measure of cellular redox state. Its biochemistry inside the cell is well mapped. Studies that supply glutathione from outside, in animals or people, are harder to interpret because extracellular glutathione is readily broken down, and human findings in that area are inconsistent.

NAD+ (Nicotinamide Adenine Dinucleotide)

NAD+, nicotinamide adenine dinucleotide, is a non-peptide coenzyme formed from two nucleotides joined through their phosphate groups. One nucleotide carries adenine and the other nicotinamide, a form of vitamin B3, and the molecule occurs in every living cell. Cells can make it from tryptophan or nicotinic acid, but mammalian cells rely mostly on a salvage pathway that recycles nicotinamide, with the enzyme NAMPT setting its pace. Identified in yeast extracts more than a century ago, it has long been central to enzymology; recent work, mostly in rodents and cell culture, concerns its roles in signalling and how its levels change with age and metabolic state. Human data on exogenous NAD+ remain limited.

How Glutathione (GSH) acts

The reactive part of glutathione is the thiol of its cysteine residue. Glutathione peroxidases use it to reduce hydrogen peroxide and lipid hydroperoxides, in the process oxidising two molecules of GSH to GSSG; glutathione reductase then regenerates GSH using NADPH. Glutathione S-transferases attach it to electrophilic compounds, the first step in a conjugation pathway that handles many drugs and foreign chemicals. It also forms mixed disulfides with cysteine residues in proteins, a modification studied as a form of redox signalling. Because the gamma-glutamyl bond resists most peptidases, breakdown begins with gamma-glutamyl transpeptidase on the outer surface of cells.

How NAD+ (Nicotinamide Adenine Dinucleotide) acts

NAD+ accepts a hydride ion to become NADH, and the NAD+/NADH pair carries electrons from glycolysis and mitochondrial dehydrogenases to complex I of the respiratory chain. Beyond this redox role, three enzyme families consume NAD+ as a substrate: the sirtuins, which remove acetyl and other acyl groups from proteins; the poly(ADP-ribose) polymerases (PARPs), which are activated by DNA strand breaks; and CD38 and related enzymes, which generate signalling molecules such as cyclic ADP-ribose. NAD+ outside cells is generally thought to be broken down by cell-surface enzymes into smaller precursors before cells take it up, so the fate of exogenous NAD+ is itself a research question.

The records side by side

• Type: Glutathione (GSH), Tripeptide; NAD+ (Nicotinamide Adenine Dinucleotide), Coenzyme (dinucleotide)
• Length: Glutathione (GSH), 3 amino acids; NAD+ (Nicotinamide Adenine Dinucleotide), not recorded
• Molecular weight: Glutathione (GSH), 307.33 g/mol; NAD+ (Nicotinamide Adenine Dinucleotide), 663.4 g/mol
• Molecular formula: Glutathione (GSH), C10H17N3O6S; NAD+ (Nicotinamide Adenine Dinucleotide), C21H27N7O14P2

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.