Alkaloids

Pyrroloquinoline Alkaloids

Pyrroloquinoline Alkaloids, Pyrroloquinoline quinone (PQQ, Methoxatin) is a compound found ubiquitously in plants, many simple and single cell eukaryotes (e.g., Yeast), and certain bacteria. Its a cofactor that was originally isolated from methylotrophic bacteria, discovered in 1964 by Hauge and its structure was determined by Kennard 15 years later.

• Pyrroloquinoline quinone (PQQ) is utilized in bacteria as a redox cycling cofactor, where it acts as the third redox cofactor in bacteria in addition to flavins and nicotinamides.
• Pyrroloquinoline quinone (PQQ) is a growth stimulant in mammals fed chemically defined diets.
• Diets deficient in Pyrroloquinoline quinone (PQQ) resulted in growth impairment, compromised immune response, abnormal reproductive performance, and metabolic inflexibility.

More Pyrroloquinoline Alkaloids Details

• Quino-proteins (PQQ-containing enzymes) have an unusual structure with radial symmetry sometimes referred to as 6-bladed (or 8-bladed) propeller structure.
• Examples of Quino-proteins are methanol dehydrogenase in bacteria that grow on methane or methanol, ethanol dehydrogenase from Acetobacter, or polyol-dehydrogenase from Gluconobacter.

• The first step of Pyrroloquinoline quinone (PQQ) biosynthesis is the linkage of glutamate and Tyrosine at the 9 and 9′ position catalyzed by the pqqE gene product.

• Remarkably, PqqE does not recruit the free Amino Acids, but as members of the PqqA polypetide chain.

• Depending on the organism PqqA is 24–39 Amino Acids long comprising the two Pyrroloquinoline quinone (PQQ) precursor Amino Acids, separated by a linker of three Amino Acids, in the middle of the polypeptide chain.

• The pqqA gene is the First gene of the pqq operon that also contains pqqE and, depending on the organism, two to five additional genes including pqqF involved in the removal of the surplus Amino Acids and the trimming of the 9- to 9′-linked glu-tyr dipeptide to mature Pyrroloquinoline quinone (PQQ).

• Biosynthesis of metabolic compounds from polypeptide chains is not uncommon in nature, the most prominent example might be the ACV tripeptide precursor of penicillins, but in contrast to PqqA these precursor peptides are produced by non-ribosomal polypeptide synthases.

• The principal source of Pyrroloquinoline quinone (PQQ) for animals is the diet. There is no evidence that Pyrroloquinoline quinone (PQQ) is made in animal tissues and organs.

• In plants, Pyrroloquinoline quinone (PQQ) comes directly from soil and soil bacteria. The major bacterial sources of Pyrroloquinoline quinone (PQQ) are methylotrophic,16 rhizobium (common soil bacteria), and acetobacter bacteria.

Functions of Alkaloids (in Plants)

• Alkaloids are nitrogen storage compounds that are involved to protect them from predators, and functioned as growth regulators and substitutes for Minerals (like Potassium and Calcium).

• When predators attack plants, the Alkaloids can interfere the predator’s Nervous System, membrane transport, Protein synthesis and enzyme activity, while under abiotic or biotic Stress Alkaloids can enhance plant Reproductive rates.

• Some of the Alkaloids may also act as herbicide by inhibiting the growth of competing plants.

Functions of Alkaloids (in Humans)

• Alkaloids are importance compounds in the human pharmaceutical industry.

For instance,

• The Alkaloid derived from beta-carboline group such as harmine has been used as Anti-Microbial, Anti-HIV and anti-parasitic.

• The Vinca Alkaloid (vinblastine and vincristine) isolated from Catharanthus roseus, berberine isolated from Coptis spp. and taxol isolated from Taxus bravifolia have been employed as Anti-Cancer drugs for treating Leukemias, Lymphomas, testicular Cancer, Breast Cancer, Lung Cancers and Kaposi’s sarcoma.

Remedies Commonly used for Alkaloid Poisoning

Black Tea

Cranesbill

Witch Hazel

Three (3) remedies commonly used for Alkaloid Poisoning.
• Black Tea
• Cranesbill
• Witch Hazel

Examples of Pyrroloquinoline Alkaloids

Burgundydrop Bonnet Mushroom

Pyrroloquinoline Alkaloids from the Fruiting Bodies of the Blood-Foot/Burgundydrop Bonnet Mushroom (Mycena haematopus)

• Mycenaflavin A (Yellow),
• Mycenaflavin B (Yellow),
• Mycenaflavin C (Yellow),
• Mycenaflavin D (Purple),

• The mycenaflavins are structurally related to mycenarubins and haematopodins, however, compared with other known fungal pyrroloquinoline Alkaloids, the mycenaflavins contain an additional double bond within the pyrroloquinoline moiety that accounts for the yellow colour of the monomeric mycenaflavins A, B, and C.

• The purple mycenaflavin D is the First known dimeric pyrroloquinoline Alkaloid with a C-C bridge between the two pyrroloquinoline units.

• Although the minor pyrroloquinoline Alkaloid constituent mycenaflavin A exhibits only moderate bioactivity against the soil bacterium Azoarcus tolulyticus, the major pyrroloquinoline Alkaloid constituent haematopodin B is similarly active as the antibiotic gentamicin.

Bleeding Bonnet Mushroom

Pyrroloquinoline Alkaloids from the Fruiting Bodies of the Bleeding Bonnet Mushroom (Mycena sanguinolenta)

• Sanguinone A (blue),
• Sanguinone A (blue),
• Sanguinolentaquinone (a new red indoloquinone Alkaloid),
• Decarboxydehydrosanguinone A (),

• The sanguinones are structurally related not only to the mycenarubins A and B, but also to a large number of marine Alkaloids such as the discorhabdins.