Flavonoids: definition, structure and classification

CONTENTS

What are flavonoids?

Flavonoids are the most abundant polyphenols in human diet, representing about 2/3 of all those ones ingested. Like other phytochemicals, they are the products of secondary metabolism of plants and, currently, it is not possible to determine precisely their number, even if over 4000 have been identified.
In fruits and vegetables, they are usually found in the form of glycosides and sometimes as acylglycosides, while acylated, methylated and sulfate molecules are less frequent and in lower concentrations.
They are water-soluble and accumulate in cell vacuoles.

Chemical structure of flavonoids

Their basic structure is a skeleton of diphenylpropane, namely, two benzene rings (ring A and B, see figure) linked by a three carbon chain that forms a closed pyran ring (heterocyclic ring containing oxygen, the C ring) with benzenic A ring. Therefore, their structure is also referred to as C6-C3-C6.

Flavonoids: the Skeleton
Fig. 1 – Skeleton of Diphenylpropane

In most cases, B ring is attached to position 2 of C ring, but it can also bind in position 3 or 4; this, together with the structural features of the ring B and the patterns of glycosylation and hydroxylation of the three rings, makes the flavonoids one of the larger and more diversified groups of phytochemicals, so not only of polyphenols, in nature.
Their biological activities, for example they are potent antioxidants, depend both on the structural characteristics and the pattern of glycosylation.

Classification

They can be subdivided into different subgroups depending on the carbon of the C ring on which B ring is attached, and the degree of unsaturation and oxidation of the C ring.
Flavonoids in which B ring is linked in position 3 of the ring C are called isoflavones; those in which B ring is linked in position 4, neoflavonoids, while those in which the B ring is linked in position 2 can be further subdivided into several subgroups on the basis of the structural features of the C ring. These subgroup are: flavones, flavonols, flavanones, flavanonols, flavanols or catechins and anthocyanins.
Finally, flavonoids with open C ring are called chalcones.

Flavonoids: the Subgroups
Fig. 2 – Flavonoid Subgroups
  • Flavones
    They have a double bond between positions 2 and 3 and a ketone in position 4 of the C ring. Most flavones of vegetables and fruits has a hydroxyl group in position 5 of the A ring, while the hydroxylation in other positions, for the most part in position 7 of the A ring or 3′ and 4′ of the B ring may vary according to the taxonomic classification of the particular vegetable or fruit.
    Glycosylation occurs primarily on position 5 and 7, methylation and acylation on the hydroxyl groups of the B ring.
    Some flavones, such as nobiletin and tangeretin, are polymethoxylated.
  • Flavonols
    Compared to flavones, they have a hydroxyl group in position 3 of the C ring, which may also be glycosylated. Again, like flavones, flavonols are very diverse in methylation and hydroxylation patterns as well, and, considering the different glycosylation patterns, they are perhaps the most common and largest subgroup of flavonoids in fruits and vegetables. For example, quercetin is present in many plant foods.
  • Flavanones
    Flavanones, also called dihydroflavones, have the C ring saturated; therefore, unlike flavones, the double bond between positions 2 and 3 is saturated and this is the only structural difference between the two subgroups of flavonoids.
    The flavanones can be multi-hydroxylated, and several hydroxyl groups can be glycosylated and/or methylated.
    Some have unique patterns of substitution, for example, furanoflavanones, prenylated flavanones, pyranoflavanones or benzylated flavanones, giving a great number of substituted derivatives.
    Over the past 15 years, the number of flavanones discovered is significantly increased.
  • Flavanonols
    Flavanonols, also called dihydroflavonols, are the 3-hydroxy derivatives of flavanones; they are an highly diversified and multisubstituted subgroup.
  • Isoflavones
    As anticipated, isoflavones are a subgroup of flavonoids in which the B ring is attached to position 3 of the C ring. They have structural similarities to estrogens, such as estradiol, and for this reason they are also called phytoestrogens.Neoflavonoids
    They have the B ring attached to position 4 of the C ring.
  • Flavanols or flavan-3-ols or catechins
    Flavanols are also referred to flavan-3-ols as the hydroxyl group is almost always bound to position 3 of C ring; they are called catechins as well.
    flavanols to have two chiral centers in the molecule, on positions 2 and 3, then four possible diastereoisomers. Epicatechin is the isomer with the cis configuration and catechin is the one with the trans configuration. Each of these configurations has two stereoisomers, namely, (+)-epicatechin and (-)-epicatechin, (+)-catechin and (-)-catechin.
    (+)-Catechin and (-)-epicatechin are the two isomers most often present in edible plants.
    Another important feature of flavanols, particularly of catechin and epicatechin, is the ability to form polymers, called proanthocyanidins or condensed tannins. The name “proanthocyanidins” is due to the fact that an acid-catalyzed cleavage produces anthocyanidins.
    Proanthocyanidins typically contain 2 to 60 monomers of flavanols.
    Monomeric and oligomeric flavanols (containing 2 to 7 monomers) are strong antioxidants.
  • Anthocyanidins
    Chemically, anthocyanidins are flavylium cations and are generally present as chloride salts.
    They are the only group of flavonoids that gives plants colors (all other flavonoids are colorless).
    Anthocyanins are glycosides of anthocyanidins. Sugar units are bound mostly to position 3 of the C ring and they are often conjugated with phenolic acids, such as ferulic acid.
    The color of the anthocyanins depends on the pH and also by methylation or acylation at the hydroxyl groups on the A and B rings.
  • Chalcones
    Chalcones and dihydrochalcones are flavonoids with open structure; they are classified as flavonoids because they have similar synthetic pathways.

References

de la Rosa L.A., Alvarez-Parrilla E., Gonzàlez-Aguilar G.A. Fruit and vegetable phytochemicals: chemistry, nutritional value, and stability. 1th Edition. Wiley J. & Sons, Inc., Publication, 2010

Han X., Shen T. and Lou H. Dietary polyphenols and their biological significance. Int J Mol Sci 2007;9:950-988. doi:10.3390/i8090950

Manach C., Scalbert A., Morand C., Rémésy C., and Jime´nez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79(5):727-47 doi:10.1093/ajcn/79.5.727

Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010;2:1231-1246. doi:10.3390/nu2121231


Polyphenols: definition, structure and classification

CONTENTS

What are polyphenols?

Polyphenols are one of the most important and certainly the most numerous among the groups of phytochemicals present in the plant kingdom.
Currently, over 8000 phenolic structures have been identified, of which more than 4000 belonging to the class of flavonoids, and several hundred occur in edible plants.
However, it is thought that the total content of polyphenols in plants is underestimated as many of the phenolic compounds present in fruits, vegetables and derivatives have not yet been identified, escaping the methods and techniques of analysis used, and the composition in polyphenols for most fruits and some varieties of cereals is not yet known.

They are present in many edible plants, both for men and animals, and it is thought to be their presence, along with that of other molecules such as carotenoids, vitamin C or vitamin E, the responsible for the healthy effects of fruits and vegetables.
In the human diet, they are the most abundant natural antioxidants, and the main sources are fruits, vegetables, whole grains, but also other types of foods and beverages derived from them, such as red wine, rich in resveratrol, the extra virgin olive oil, rich in hydroxytyrosol, chocolate or tea, in particularly green tea, rich in epigallocatechin gallate (EGCG).

Chemical structure of polyphenols

The term polyphenols refers to a wide variety of molecules that can be divided into many subclasses, subdivisions that can be made on the basis of their origin, biological function, or chemical structure.
Chemically, they are compounds with structural phenolic features, which can be associated with different organic acids and carbohydrates.

Polyphenols: Phenolic Skeleton
Fig. 1 – Phenol

In plants, the most part of them are linked to sugars, and therefore they are in the form of glycosides. Carbohydrates and organic acids can be bound in different positions on polyphenol skeletons.
Among polyphenols, there are simple molecules, such as phenolic acids, or complex structures such as condensed tannins, that are highly polymerized molecules.

Classification

They can be classified into different classes, according to the number of phenolic rings in their structure, the structural elements that bind these rings each others, and the substituents linked to the rings.

Polyphenols: Flavonoid Skeleton
Fig. 2 – Flavonoid Skeleton

Therefore, two main groups can then be identified: the flavonoids group and the non-flavonoid group.
Flavonoids share a structure formed by two aromatic rings, indicated as A and B, linked together by three carbon atoms forming an oxygenated heterocycle, the C ring; they can be further subdivided into six main subclasses, as a function of the type of heterocycle (the C ring) that is involved:

Non-flavonoids can be subdivided into:

  • simple phenols
  • phenolic acids
  • benzoic aldehydes
  • hydrolyzable tannins
  • acetophenones and phenylacetic acids
  • hydroxycinnamic acids
  • coumarins
  • benzophenones
  • xanthones
  • stilbenes;
  • lignans
  • secoiridoids

Variability of polyphenol content of plant and plant products

Although several classes of phenolic molecules, such as quercetin (a flavonol), are present in most plant foods (tea, wine, cereals, legumes, fruits, fruit juices, etc.), other classes are found only in a particular type of food (e.g. flavanones in citrus, isoflavones in soya, phloridzin in apples, etc.).

Polyphenols: Quercetin
Fig. 3 – Quercetin

However, it is common that different types of polyphenols are in the same product; for example, apples contain flavanols, chlorogenic acid, hydroxycinnamic acids, glycosides of phloretin, glycosides of quercetin and anthocyanins.
The polyphenol composition may also be influenced by other parameters such as environmental factors, the degree of ripeness at harvest time, household or industrial processing, storage, and plant variety. From currently available data, it seems that the fruits with the highest content of polyphenols are strawberries, lychees and grapes, and the vegetables are artichokes, parsley and brussels sprouts. Melons and avocados have the lowest concentrations.

References

de la Rosa L.A., Alvarez-Parrilla E., Gonzàlez-Aguilar G.A. Fruit and vegetable phytochemicals: chemistry, nutritional value, and stability. 1th Edition. Wiley J. & Sons, Inc., Publication, 2010

Han X., Shen T. and Lou H. Dietary polyphenols and their biological significance. Int J Mol Sci 2007;9:950-988. doi:10.3390/i8090950

Manach C., Scalbert A., Morand C., Rémésy C., and Jime´nez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79(5):727-47 doi:10.1093/ajcn/79.5.727

Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010;2:1231-1246. doi:10.3390/nu2121231


Glycogen: an efficient storage form of energy in aerobic conditions

What is the net energy yield for the oxidation of a glucose unit from glycogen in aerobic conditions?

In aerobic conditions, the oxidation of a free glucose to CO2 and H2O (glycolysis, Krebs cycle and oxidative phosphorylation) leads to the net production of about 30 molecules of ATP.

Aerobic Conditions
Glycogen Structure

Glucose from the action of glycogen phosphorylase: glucose-1-phosphate release (about 90% of the removed units)

Glycogen synthesis from free glucose costs two ATP units for each molecule; a glucose-1-phosphate is released by the action of glycogen phosphorylase with recovering/saving one of the two previous ATP molecules.
Therefore in aerobic condition, the oxidation of glucose starting from glucose-6-phosphate and not from free glucose yields 31 ATP molecules and not 30 (one ATP instead of two is expended in the activation phase, 30 ATP are produced during Krebs cycle and oxidative phosphorylation: 31 ATP gained).
The net rate between cost and yield is 1/31 (an energy conservation of about 97%).
The overall reaction is:

glycogen(n glucose residues) + 31 ADP + 31 Pi → glycogen(n-1 glucose residues) + 31 ATP + 6 CO2 + 6 H2O

If we combine glycogen synthesis, glycogen breakdown and finally the oxidation of glucose to CO2 and H2O we obtain 30 molecules of ATP per stored glucose unit, that is the overall reaction is:

glucose + 29 ADP + 30 Pi → 29 ATP + 6 CO2 + 6 H2O

Glucose from the action of debranching enzyme: free glucose release (about 10% of the removed units)

The net yield in ATP between glycogen synthesis and breakdown is two ATP molecules expended because of free glucose is released.
In this case the oxidation of glucose starts from the not-prephosphorylated molecule so we obtain 30 ATP molecules.
The net rate between cost and yield is 2/30 (a energy conservation of about 93,3%).
Considering the oxidation of the glucose units from glycogen to CO2 and H2O we have an energy conservation of:

1-(((1/31)*0,9)+((2/30)*0,1))=0,9643

Conclusion

In aerobic conditions, there is the conservation of about 97% of energy into the glycogen molecule, an extremely efficient storage form of energy.

References

Arienti G. “Le basi molecolari della nutrizione”. Seconda edizione. Piccin, 2003

Berg J.M., Tymoczko J.L., and Stryer L. Biochemistry. 5th Edition. W. H. Freeman and Company, 2002

Cozzani I. and Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006

Giampietro M. “L’alimentazione per l’esercizio fisico e lo sport”. Il Pensiero Scientifico Editore, 2005

Mahan LK, Escott-Stump S.: “Krause’s foods, nutrition, and diet therapy” 10th ed. 2000

Mariani Costantini A., Cannella C., Tomassi G. “Fondamenti di nutrizione umana”. 1th ed. Il Pensiero Scientifico Editore, 1999

Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 4th Edition. W.H. Freeman and Company, 2004

Stipanuk M.H.. “Biochemical and physiological aspects of human nutrition” W.B. Saunders Company-An imprint of Elsevier Science, 2000