FLAVONOIDS

     Flavonoids have a basic skeleton of 15 carbon terdiriu atomkarbon, in which two benzene rings (C6) bound to a chain of propane (C3) to form an arrangement of C6-C3-C6. This arrangement can produce three kinds of structure of flavonoid compounds. This arrangement can produce three jenisstruktur, the 1.3-diarilpropan or flavonoids, 1.2-diarilpropan or isoflavones, dan1,1-diarilpropan or neoflavon.

      Of the various types of flavonoids, flavones, flavonols, and anthocyanidins are the kind that are found in nature, so it is often stated as the main flavonoids. While the types of flavonoids in nature in limited quantities is calkon, Auron, katecin, flavanones, and leukoantosianidin.

     The number of flavonoid compounds in nature and not due to the many variations in structure, but are caused by different levels of hydroxylation, alkoksilasi, or glycosylation of the structure.

1. Biosynthesis of Flavonoids

     All variants of the flavonoid biosynthesis correlated because the groove itself, yaiut linesSikimat and acetate-malonate pathway. The model of the biosynthesis of flavonoids has beensuggested by Birch. According Birch, the steps of the biosynthesis of flavonoids pertamadari aC₆-C₃ berkombinasi units with three units C₂ menghasilakan -C₃-C₆ units (C₂ + C₂ + C₂). C₁₅framework that has been dihasilakan darikombinasi oxygen containing functional groups onyangdiperlukan position. A ring of the flavonoid structure derived from the polyketide route,yaitukondensasi of three units of acetate or malonate. While the B ring and three atomkarbon of the propane chain is Adari phenylpropanoid path (via shikimic.) Therefore, the basic structure of the carbon product darikombinasi biosynthesis of flavonoids between two major avenues for the aromatic ring, called shikimic and acetate-malonate path . As a result of various perubahanyangcaused by enzymes, the third carbon atom of the propane chain can produce a variety offunctional groups, such as double bonds, hydroxyl, carbonyl groups, and so on.

Structure of flavonoids undergo secondary reactions, sepertihidroksilasi, oxidation(including training carbonyl), glycosylation, methylation, isoprenilasi, cyclization, and the other for the treatment of enzimyang present in the organism. The product of the enzymatic reactiondapatmenghasilkan flavonoid compounds with different types kerangkadasar different as shownon the classification of flavonoids klasifikasiatau above (Tukiran, 2010)

Figure 9. Principal reaction Flavonoid Biosynthesis

According biosynthesis, the formation of flavonoid started denganmemperpanjang unitsfenilpropanaid (C3-C6) derived from p-amino derivatives sinamatseperti kumarat, times kafeatacid, ferulic acid, or asamsinapat. The experiments have also shown that calkon and flavanonesisomer are comparable also serves as an intermediate in the biosynthesis of various types of otherflavonoids.

FLAVONOIDS AND COCAINE

A. FLAVONOIDS

           Flavonoids are compounds that consists of 15 carbon atoms that are scattered in theplant world. More than 2000 flavonoids derived from plants have been identified,but there are three general groups studied, namely anthocyanins, flavonols, andflavones. 

            Anthocyanins (from Greek anthos, flower and kyanos, dark blue) aregenerally colored pigment found in red flowers, purple, and blue. These pigments are also present in many other parts of the plant, for example, certain fruit , stems,leaves and even roots. Flavnoid often found in epidermal cells.  Most of theflavonoids terhimpn in plant cell vacuoles synthesis although there are places outside the vacuole.

            Anthocyanins and other flavonoids attracted many geneticists because it is possibleto connect the morphological differences between closely related species in thesame genus as the type of flavonoids it contains.  Flavonoids are found in related species within a genus provide information for experts taxonomy formegelompokkan and determine the evolution of the plant lines.  Especially the bluewavelength of light increases the formation of flavonoids and flavonoid improvecrop resistance to UV radiation.  Quercetin and myricetin, a type of flavonoid that protects Caco-2 cells were found in the digestive tract of a double chain of DNAoxidation and antioxidant properties that protect from oxidative stress kolonosit.

B. COCAINE

           Cocaine produced is Erythroxylum coca plant. The content of the compound is a plant alkaloid called cocaine. The content of alkaloids was 0.7 to 2.5% (40-50% is (-)-cocaine. Nature is a psychostimulant (amphetamine like properties).

Biosynthesis cation N-methyl-pyrrolinium

             Cation N-methyl-pirolinium is an important precursor in the biosynthesis of cocaine. Biosynthesis starts from L-Glutamine, which is derived to L-ornithine in plants.

L-ornithine is converted into L-arginine, which is then decarboxylated via PLP to form agmatine. Hydrolysis is derived imine N-carbamoylputrescine followed by hydrolysis of urea to form putrescine. Separate pathways to convert ornithine to putrescine in plants and animals have been known. N-SAM-SAM methylation of putrescine gives the N-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase produces aminoaldehyde it. Melaului Schiff base formation forming cation N-methyl-Δ1-pyrrolinium.

Biosynthesis of Cocaine

                Additional carbon atoms required for the synthesis of cocaine derived from acetyl-CoA, with the addition of two acetyl-CoA units for the cation N-methyl-Δ1-pyrrolinium.

The first Addisi Mannich reaction, ie enolate anion from acetyl-CoA acting as a nucleophile to cation pyrrolinium. Addisi both going through Claisen condensation produces a racemic mixture of 2-substituted pyrrolidine.

          On the formation of tropinone from racemic ethyl [2,3-13C2] 4 (Nmethyl-2-pyrrolidinyl)-3-oxobutanoate there is no specific stereoisomer specificity. However, the biosynthesis of cocaine, only the (S)-enantiomer can do cyclization to form ring systems tropan cocaine. Then the oxidation reaction, which regenerates pyrrolinium cation and formation of enolate anion, and an intramolecular Mannich reaction. The ring system tropan hydrolyses, SAM-dependent methylation, and reduction of NADPH for the formation methylecgonine. Cluster benzoyl required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid. Benzoyl-CoA then combines the two units to form cocaine.

Psychological impact

             Cocaine is a stimulant drug (psychostimulants) are the most potent. Common behavior for under the influence of cocaine can include hyperactivity, joy, and powerful, alertness, confidence and increased sexual activity. Users can also behave opinionated anyway, feeling invincible and be aggressive and quarrelsome. Fatal condition that can occur from a high sensitivity to cocaine or a massive overdose. A few hours after the last use, sense of upheaval and depression may occur.

Addiction

             Based on Definitions of the American Society of Addiction Medicine, some drugs cause kacanduan grouped as follows:

1. Stimulants (psychic addiction, moderate to severe; withdrawal is purely psychological and Psychosomatic):
- Amphetamine and methamphetamine
- Cocaine
- Nicotine
- Caffeine
2. Sedatives an hinotik (psychic addiction, mild to severe, and physiological addiction, severe; abrupt withdrawal may be fatal):
- Alcohol
- Barbiturates
- Benzodiazepines are especially flunitrazepam, triazolam, temazepam and nimetazepam Z drug like zimovane.
- Metakualon and hypnotic-sedative related kuinazolin.
Opiot and opioid analgesics (psychic addiction, mild to severe, physiological addiction, mild to severe; abrupt withdrawal is unlikely to be fatal):
- Morphine and codeine
- Semisynthetic opiates such as heroin (diacetylmorphine; morphine diacetate), oxycodone, buprenorphine, and hydromorphone.
- Opioid total synthesis, such as fentanyl, meperidine / pethidine, and methadone.
Drugs in bold are the ones alkaloid compounds. An article in the journal Lancet compared the 20 dangerous and addictive drugs, using a scale of 0 to 3 for physical addiction, psychological addiction, and pleasure to create a mean score for addiction.
Highest rank was on morphine.

Mechanism of action

             Cocaine modify the action of dopamine in the brain. Dopamine-rich area is the ventral tegmental area, the nucleus accumbens and the caudate nucleus - these areas are collectively called the brain's 'reward pathway'. Cocaine binds to the dopamine transporter re-uptake at the pre-synaptic membrane of the dopaminergic neurons. This bond inhibiting dopamine removal from the synaptic cleft and the next is degraded by monoamine oxidase (MAO) in the nerve terminal. Dopamine is still lagging behind in the synaptic cleft and free form binds to receptors on the post synaptic membrane, causing further nerve impulses. The increase in the activation of dopaminergic reward pathways trigger feelings of euphoria.

Cocaine acts on the pleasure circuit to prevent reabsorption of dopamine neurotranmitter after being released from nerve cells. Normally, neurons release dopamine release in the pleasure circuit, then pass through the synapse to another neuron stimulate pleasure circuits. Once this process is completed, will be taken again by the dopamine transporter molecules and bring back the original neurons.
Cocaine binds transpoter turns so as to prevent the reabsorption of dopamine. This causes an increase in dopamine in the synapse, the result is a strong feeling emerged and even euphoria.

Excess dopamine accumulates in the synapses of neurons that have led to decreased number of dopamine receptors receptors they make. It was named after down-regulation. When cocaine is not given and jumlahna decreased to normal conditions (low concentration), the small number of available receptors for the neurotransmitter dopamine to be not enough to activate nerve cells. During the "craving," the experience will be very strong addict and need medication to achieve the level of dopamine back. Cocaine can also bind to other neurotransmitters, including serotonin and norepinephrine, and blocking reuptake.
Cocaine found to specifically affect the prefrontal cortex and the amygdala, which is involved in memory and learning aspects. The amygdala has been associated with the emotional aspects of memory. Experts believe that the neural networks involved in parts of the brain that react to the environment and enable memory, and triggers biochemical changes in producing cocaine craving.