mevalonate pathway

The biosynthesis of isopentenyl pyrophosphate (IPP) occurs via two distinct routes: the mevalonate pathway (MVA pathway, this pathway) and the methylerythritol phosphate pathway (MEP pathway) .In the former, IPP is synthesized from the condensation of three acetyl-CoA molecules; in contrast the MEP pathway occurs via the condensation of pyruvate and D-glyceraldehyde 3-phosphate. For many years, the MVA pathway was considered to be the sole source of IPP in all living organisms, however, several inconsistencies led to the discovery of the MEP pathway in bacteria and plants. In the latter the MVA pathway is located in the cytosol whilst the MEP pathway is found in plastids.

In eukaryotic cells, the mevalonate pathway leads to plant sterol biosynthesis , superpathway of ergosterol biosynthesis and dolichols via the formation of farnesyl diphosphate (FPP). IPP from this pathway is also used to synthesize cytosolic geranylgeranyl diphosphate (GGPP) which is used (along with FPP) for the prenylation of proteins. In plants, the mevalonate pathway is also a source of isoprene units for the biosynthesis of a variety of terpenoids (cytokinins, brassinosteroids, sesquiterpenes, polyprenoids). However, the MVA pathway appears not to function independently from the MEP pathway but rather interacts through metabolic cross-talk.

This pathway described as mevalonat pathway displays the enzymatic steps that lead to mevalonate and the further conversion towards dimethylallyl pyrophosphate (DMPP) one of the crucial intermediates that give rise to several terpenoid and plant hormone pathways. Most of the enzymes characterized in Arabidopsis thaliana from this pathway have been demonstrated to be fully functional, largely through functional complementation of bacterial and yeast mutant strains.

The first enzyme of the pathway, i.e. acetoacetyl (AcAc)-CoA thiolase (AACT; EC 2.3.1.9) that catalyzes the condensation of two acetyl-CoA to form acetoacetyl-CoA has not yet been identified in Arabidopsis. The following enzyme hydroxymethylglutaryl-CoA synthase (HMGS) catalyzes the formation of the thermodynamically favourable aldol condensation of one molecule of AcAc-CoA with acetyl-CoA to form one molecule of S-HMG-CoA .The proposal that the conversion from acetyl-CoA to hydroxymethylglutaryl-CoA comprising two enzymatic steps is carried out by a single enzyme was not confirmed as the yeast mutant deficient in acetoacetyl-CoA thiolase could not be functionally complemented. The isolation and characterization of hydroxymethylglutaryl-CoA synthase from Brassica juncea indicates that those conversions are conducted by two independent proteins.

The last enzymatic step to form mevalonate is accomplished by hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which are encoded in Arabidopsis by two genes HMG1 and HMG2 from which HMG1 forms two isoforms, HMGR1S and HMGR1L. The enzyme is located within the Endoplasmatic Reticulum (ER) but has also been found within new and so far unidentified vesicular structures in the cytoplasm and within the vacuole of differentiated cotyledon cells .

The remaining steps towards DMPP comprise two phosphorylation steps to convert mevalonate to mevalonate-5-diphosphate. Following the ATP-dependent decarboxylation of mevalonate-5-diphosphate to generate isopentenyl-pyrophosphate (IPP) the final enzyme of the pathway, isopentenyl-diphosphate delta-isomerase encoded by two genes (IPP1, IPP2) forms dimethylallyl pyrophosphate (DMPP)

Flavonoid biosynthetic pathway

Flavonoid biosynthetic pathway

Flavonoids are synthesized via the phenylpropanoid pathway. Phenylalanine ammonia lyase (PAL) catalyzes the conversion of phenylalanine to cinnamate. PAL also shows activity with converting tyrosine to p-coumarate, albeit to a lower efficiency. The cinnamate 4-hydroxylase (C4H) catalyzes the synthesis of p-hydroxycinnamate from cinnamate and 4-coumarate:CoA ligase (4CL) converts p-coumarate to its coenzyme-A ester, activating it for reaction with malonyl CoA. The flavonoid biosynthetic pathway starts with the condensation of one molecule of 4-coumaroyl-CoA and three molecules of malonyl-CoA, yielding naringenin chalcone. This reaction is carried out by the enzyme chalcone synthase (CHS). Chalcone is isomerised to a flavanone by the enzyme chalcone flavanone isomerase (CHI). From these central intermediates, the pathway diverges into several side branches, each resulting in a different class of flavonoids. Flavanone 3-hydroxylase (F3H) catalyzes the stereospecific 3ß-hydroxylation of (2S)-flavanones to dihydroflavonols. For the biosynthesis of anthocyanins, dihydroflavonol reductase (DFR) catalyzes the reduction of dihydroflavonols to flavan-3,4-diols (leucoanthocyanins), which are converted to anthocyanidins by anthocyanidin synthase (ANS). The formation of glucosides is catalyzed by UDP glucose-flavonoid 3-o-glucosyl transferase (UFGT), which stabilize the anthocyanidins by 3-O-glucosylation (Harborne 1994, Bohm 1998). The overview of the flavonoid pathway is presented in Fig 1B. There is evidence that the enzymes involved in flavonoid metabolism might be acting as membrane-associated multienzyme complexes, which has implications on the overall efficiency, specificity, and regulation of the pathway (Stafford 1991, Winkel-Shirley 1999, 2001).

Studies of the flavonoid pathway range from classical genetic analysis of flower color inheritance patterns by Mendel, through the establishment of their chemical structures, to efforts to understand the factors involved in their biochemical synthesis (Bohm 1998). Basic knowledge of the flavonoid biosynthesis was gained from experimental studies using radio-labeled precursors at the end of 1950’s. The development of more sophisticated methods in analytical chemistry and enzymology, and later in gene technology, has produced a vast number of studies and detailed information of the flavonoid biosynthesis in several plant species. The flavonoid biosynthetic pathway has been comprehensively reviewed (e.g. by Dooner & Robbins 1991, Koes et al. 1994, Holton & Cornish 1995, Molet al. 1998, Weisshaar & Jenkins 1998, Winkel-Shirley 2001).

The first gene isolated from the flavonoid biosynthetic pathway was a CHS gene from parsley (Petroselinum hortense) (Kreuzaler et al. 1983). Transcriptional control of the structural genes of the flavonoid biosynthetic pathway has been most intensively studied in relation to the biosynthesis of anthocyanins. Groundbreaking research concerning the expression of the structural and regulatory genes of the flavonoid pathway has been done with maize (Zea mays) (Goff et al. 1990, Taylor et al. 1990, Tonelli et al. 1991), arabidopsis (Arabidopsis thaliana) (Shirley et al. 1992) and with ornamental plants like snapdragon (Antirrhinum majus) (Martin et al.1991), petunia (van der Krol et al. 1988) and gerbera (Elomaa et al. 1993, Helariutta et al. 1993, 1995). Naturally occurring flavonoid mutants and variants, or genetically transformed mutant plants have been important tools in several investigations clarifying the functions of the flavonoid pathway genes (Shirley et al. 1995, Tanaka et al. 1998).

The expression of flavonoid pathway genes in fruit tissues has been studied on grape (Vitis vinifera) (Boss et al. 1996, Kobayashi et al. 2001), citrus (Citrus unshiu Marc.) (Moriguchi et al. 2001), and strawberry plants (Fragariaspp.) (Manning 1998, Aharoni et al. 2001). The scarcity of studies in this area may be due to a difficulty caused by the special features of the fruit tissues, e.g. the richness of different secondary metabolites and RNases, which may hinder the easy application of the molecular biological research methods.

Figure 1. A) The structures of selected flavonoid classes. B) A schematic presentation of the flavonoid biosynthetic pathway. Enzyme abbreviations: PAL, phenylalanine ammonia-lyase; C4H, cinnamate 4-hydroxylase; 4CL, 4-coumaroyl:CoA ligase; CHS, chalcone synthase; CHI, chalcone isomerase; F3H, flavanone 3-hydroxylase; DFR, dihydroflavonol 4-reductase; ANS, anthocyanidin synthase; UFGT, UDP glucose-flavonoid 3-o-glucosyl transferase.

Natrium

Sejarah

(Inggris, soda; Latin, sodanum, obat sakit kepala). Sebelum Davy berhasil mengisolasi unsur ini dengan cara elektrolisis soda kaustik, natrium (unsur ini disebut sodium dalam bahasa Inggris), telah dikenal dalam berbagai suatu senyawa.

Sumber
Natrium banyak ditemukan di bintang-bintang. Garis D pada spektrum matahari sangat jelas. Natrium juga merupakan elemen terbanyak keempat di bumi, terkandung sebanyak 2.6% di kerak bumi. Unsur ini merupakan unsur terbanyak dalam grup logam alkali.

Jaman sekarang ini, sodium dibuat secara komersil melalui elektrolisis fusi basah natrium klorida. Metoda ini lebih murah ketimbang mengelektrolisis natrium hidroksida, seperti yang pernah digunakan beberapa tahun lalu.

Sifat-sifat
Natrium, seperti unsur radioaktif lainnya, tidak pernah ditemukan tersendiri di alam. Natrium adalah logam keperak-perakan yang lembut dan mengapung di atas air. Tergantung pada jumlah oksida dan logam yang terkekspos pada air, natrium dapat terbakar secara spontanitas. Lazimnya unsur ini tidak terbakar pada suhu dibawah 115 derajat Celcius.

Kegunaan
Logam natrium sangat penting dalam fabrikasi senyawa ester dan dalam persiapan senyawa-senyawa organik. Logam ini dapat di gunakan untuk memperbaiki struktur beberapa campuran logam, dan untuk memurnikan logam cair.

Campuran logam natrium dan kalium, NaK, juga merupakan agenheat transfer (transfusi panas) yang penting.

Senyawa-senyawaSenyawa yang paling banyak ditemukan adalah natrium klorida (garam dapur), tapi juga terkandung di dalam mineral-mineral lainnya seperti soda niter, amphibole, zeolite, dsb.

Senyawa natrium juga penting untuk industri-industri kertas, kaca, sabun, tekstil, minyak, kimia dan logam. Sabun biasanya merupakan garam natrium yang mengandung asam lemak tertentu. Pentingnya garam sebagai nutrisi bagi binatang telah diketahui sejak zaman purbakala.

Di antara banyak senyawa-senyawa natrium yang memiliki kepentingan industrial adalah garam dapur (NaCl), soda abu (Na₂CO₃), baking soda (NaHCO₃), caustic soda (NaOH), Chile salpeter(NaNO₃), di- dan tri-natrium fosfat, natrium tiosulfat (hypo, Na₂S₂O₃ . 5H₂0) and borax (Na₂B₄O₇. 10H₂O).

Isotop-isotop
Ada tiga belas isotop natrium. Kesemuanya tersedia di Los Alamos National Laboratory.

Penanganan
Logam natrium harus ditangani dengan hati-hati. Logam ini tidak dapat diselubungi dalam kondisi inert sehingga kontak dengan air dan bahan-bahan lainnya yang membuat natrium bereaksi harus dihindari.

Sumber 
http://periodic.lanl.gov/

FINAL EXAMINATION NATURAL PRODUCT CHEMISTRY

1.    Fats generally are solid while the oil is liquid phase,however both are equally triglyceride.explain why the form of two different triglyceride, and point out important factors that determine the form of fat?

Answer :

Triglycerides in the fat oil

Can be either solid or liquid depending on the composition of the constituent fatty acids. Liquid vegetable oil because it contains unsaturated fatty acids, while animal fats are generally solid at room temperature because it contains unsaturated fatty acids.

Fat oil

Triglycerides are composed of a mixture of esters of glycerol and long chain fatty acids. Fat if the oil will produce three molecular hydrolyzed long-chain fatty acids and a glycerol molecule.

Triglycerides oil fatty

Derived from various sources have physico-chemical properties are different from each other that occurs because of differences in the number and types of esters contained therein.

Triglycerides in the fat oil

Did not differ in their chemical composition differing only in shape or form. Triglycerides are called oils when melted at room temperature and is called solid if it freezes at room temperature.

There are many different kinds of fats, but each is a variation on the same chemical structure. All fats are derivatives of fatty acids and glycerol. The molecules are called triglycerides, which are triesters of glycerol (an ester being the molecule formed from the reaction of the carboxylic acid and an organic alcohol). As a simple visual illustration, if the kinks and angles of these chains were straightened out, the molecule would have the shape of a capital letter E. The fatty acids would each be a horizontal line; the glycerol "backbone" would be the vertical line that joins the horizontal lines. Fats therefore have "ester" bonds.

The properties of any specific fat molecule depend on the particular fatty acids that constitute it. Different fatty acids are composed of different numbers of carbon and hydrogen atoms. The carbon atoms, each bonded to two neighboring carbon atoms, form a zigzagging chain; the more carbon atoms there are in any fatty acid, the longer its chain will be. Fatty acids with long chains are more susceptible to intermolecular forces of attraction (in this case, van der Waals forces), raising its melting point. Long chains also yield more energy per molecule when metabolized.

Saturated and unsaturated fats

A fat's constituent fatty acids may also differ in the C/H ratio. When all three fatty acids have the formula C_nH_(2n+1)CO₂H, the resulting fat is called "saturated". Values of n usually range from 13 to 17. Each carbon atom in the chain is saturated with hydrogen, meaning they are bonded to as many hydrogens as possible. Unsaturated fats are derived from fatty acids with the formula C_nH_(2n-1)CO₂H. These fatty acids contain double bonds within carbon chain. This results in an "unsaturated" fatty acid. More specifically, it would be amonounsaturated fatty acid. Polyunsaturated fatty acids would be fatty acids with more than one double bond; they have the formula, C_nH_(2n-3)CO₂H and C_nH_(2n-5)CO₂H. Unsaturated fats can be converted to saturated ones by the process of hydrogenation. This technology underpinned the development of margerine.

Saturated and unsaturated fats differ in their energy content and melting point. Since unsaturated fats contain fewer carbon-hydrogen bonds than saturated fats with the same number of carbon atoms, unsaturated fats will yield slightly less energy during metabolism than saturated fats with the same number of carbon atoms. Saturated fats can stack themselves in a closely packed arrangement, so they can freeze easily and are typically solid at room temperature. For example, animal fats tallow and lard are high in saturated fatty acid content and are solids. Olive and linseed oils on the other hand are highly unsaturated and are oily.

Trans fats

There are two ways the double bond may be arranged: the isomer with both parts of the chain on the same side of the double bond (thecis-isomer), or the isomer with the parts of the chain on opposite sides of the double bond (the trans-isomer). Most trans-isomer fats (commonly called trans fats) are commercially produced. Trans fatty acids are rare in nature. The cis-isomer introduces a kink into the molecule that prevents the fats from stacking efficiently as in the case of fats with saturated chains. This decreases intermolecular forces between the fat molecules, making it more difficult for unsaturated cis-fats to freeze; they are typically liquid at room temperature. Trans fats may still stack like saturated fats, and are not as susceptible to metabolization as other fats. Trans fats may significantly increase the risk of coronary heart disease.

2.    How a primary metabolite can be converted in the mecto secondary metabolites. What is the basic idea and how the machanism could be described?

Answer:

Primary metabolite  can be converted into secondary metabolisme from the reaction the fundamental processes of photosynthesis, glycolysis, and the Krebs cycle are tapped off from energy-generating processes to provide biosynthetic intermediates.To make biosynthesis intermediets needs the buillding blocks. By far the most important building blocks employed in the biosynthesis of secondary metabolites are derived from the intermediates acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid, and methylerythritol phosphate. These are utilized respectively in the acetate, shikimate, mevalonate, and methylerythritol phosphate pathways, Acetyl-CoA is formed by oxidative decarboxylation of the glycolytic pathway product pyruvic acid. It is also produced by the β-oxidation of fatty acids, effectively reversing the process by which fatty acids are themselves synthesized from acetyl-CoA. Important secondary metabolites formed from the acetate pathway include phenols, prostaglandins, and macrolide antibiotics, together with various fatty acids and derivatives at the primary–secondary metabolism interface. Shikimic acid is produced from a combination of phosphoenolpyruvate, a glycolytic pathway intermediate, and erythrose 4-phosphate from the pentose phosphate pathway. The reactions of the pentose phosphate cycle may be employed for the degradation of glucose, but they also feature in the synthesis of sugars by photosynthesis. The shikimate pathway leads to a variety of phenols, cinnamic acid derivatives, lignans, and alkaloids. Mevalonic acid is itself formed from three molecules of acetyl-CoA, but the mevalonate pathway channels acetate into a different series of compounds than does the acetate pathway. Methylerythritol phosphate arises from a combination of two glycolytic pathway intermediates, namely pyruvic acid and glyceraldehyde 3-phosphate by way of deoxyxylulose phosphate. The mevalonate and methylerythritol phosphate pathways are together responsible for the biosynthesis of a vast array of terpenoid and steroid metabolites.

In addition to acetyl-CoA, shikimic acid, mevalonic acid, and methylerythritol phosphate, other building blocks based on amino acids are frequently employed in natural product synthesis. Peptides, proteins, alkaloids, and many antibiotics are derived from amino acids, and the origins of some of the more important amino acid components of these are briefly indicated in Figure 2.1. Intermediates from the glycolytic pathway and the Krebs cycle are used in constructing many of them, but the aromatic amino acids phenylalanine, tyrosine, and tryptophan are themselves products from the shikimate pathway. Ornithine, an amino acid not found in proteins, and its homologue lysine, are important alkaloid precursors and have their origins in Krebs cycle intermediates. Of special significance is the appreciation that secondary metabolites can be synthesized by combining several building blocks of the same type, or by using a mixture of different building blocks. This expands structural diversity and, consequently, makes subdivisions based entirely on biosynthetic pathways rather more difficult. A typical natural product might be produced by combining elements from the acetate, shikimate, and methylerythritol phosphate pathways.

3.    Hormone progesterone is essential for survival tha pregnancy,these hormones are derived from a steroid biogenetically.Explain the logic of chemical reactions which may occur in the formation of progesterone?

Answer:

In mammals, progesterone (6), like all other steroid hormones, is synthesized from pregnenolone (3), which in turn is derived fromcholesterol (1) (see the upper half of the figure to the right).

Cholesterol (1) undergoes double oxidation to produce 20,22-dihydroxycholesterol (2). This vicinal diol is then further oxidized with loss of the side chain starting at position C-22 to produce pregnenolone (3). This reaction is catalyzed by cytochrome P450scc. The conversion of pregnenolone to progesterone takes place in two steps. First, the 3-hydroxyl group is oxidized to a keto group (4) and second, the double bond is moved to C-4, from C-5 through a keto/enol tautomerizationreaction.^[14] This reaction is catalyzed by 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase.

Progesterone in turn (see lower half of figure to the right) is the precursor of the mineralocorticoid aldosterone, and after conversion to17-hydroxyprogesterone (another natural progestogen) of cortisol and androstenedione. Androstenedione can be converted totestosterone, estrone and estradiol.

4.    Many alkaoid are toxic to other organisms. Thay often have pharmacological effects and are used as medication,as recreational drug,or in entheeogenic ritual.

Answer:

Isoquinoline alkaloids are tyrosine-derived plant alkaloids with an isoquinoline skeleton. Among them benzylisoquinoline alkaloids form an important group with potent pharmacological activity, including analgesic compounds of morphine and codeine, and anti-infective agents of berberine, palmatine, and magnoflorine. Biosynthesis of isoquinoline alkaloids proceeds via decarboxylation of tyrosine or DOPA to yield dopamine, which together with 4-hydroxyphenylacetaldehyde, an aldehyde derived from tyrosine, is converted to reticuline, an important precursor of various benzylisoquinoline alkaloids.

biosintesis alkaloid tirosin

biosintesis alakoid piperidin

biosintesis alkaoid dari nikotin

Pendahuluan
Apakah kimia organik itu? Mengapa begitu banyak orang
mempelajari kimia organik dan mengapa pula kita perlu
mempelajarinya? Jawabannya sangat sederhana, karena semua
organisme hidup tersusun atas senyawa-senyawa
organik. Sebagai contohnya, rambut yang
menghias kepala kita, kulit, otot, dan DNA yang
mengontrol penurunan genetik, serta obat,
semuanya merupakan senyawa organik.
Sejarah tentang kimia organik diawali sejak pertengahan abad
17. pada waktu itu, tidak dapat dijelaskan perbedaan antara senyawa
yang diperoleh dari organisme hidup (hewan dan tumbuhan) dengan
1
12 St. Layli Prasojo, S.Farm., Apt.
senyawa yang diperoleh dari bahan-bahan mineral. Senyawa yang
diperoleh dari tumbuhan dan hewan sangat sulit diisolasi. Ketika
dapat dimurnikan, senyawa-senyawa yang diperoleh tersebut sangat
mudah terdekomposisi dari pada senyawa yang diperoleh dari bahanbahan
mineral. Seorang ahli kimia dari Swedia, Torbern Bergman,
pada tahun 1770 mengekspresikan penjelasan di atas sebagai
perbedaan antara senyawa organik dan anorganik. Selanjutnya,
senyawa organik diartikan sebagai senyawa kimia yang diperoleh dari
makhluk hidup.
Banyak ahli kimia pada masa itu hanya menjelaskan perbedaan
senyawa organik dan senyawa anorganik dalam hal bahwa senyawa
organik harus mempunyai energi vital (vital force) sebagai hasil dari
keaslian mereka dalam tubuh makhluk hidup. Salah satu akibat dari
energi vital ini adalah para ahli kimia percaya bahwa senyawa organik
tidak dapat dibuat maupun dimanipulasi di laboratorium
sebagaimana yang dapat dilakukan terhadap senyawa anorganik.
Teori vitalitas ini kemudian mengalami perubahan ketika Michael
Chevreul (1816) menemukan sabun sebagai hasil reaksi antara basa
dengan lemak hewani. Lemak hewani dapat dipisahkan dalam
beberapa senyawa organik murni yang disebut dengan asam lemak.
Untuk pertama kalinya satu senyawa organik (lemak) diubah menjadi
senyawa lain (asam lemak dan gliserin) tanpa intervensi dari energi
vital.
Kimia Organik I 13
NaOH
H2O
Lemak hewani Sabun + Gliserin
Sabun H3O Asam Lemak
Beberapa tahun kemudian, teori vitalitas semakin melemah
ketika Friedrich Wohler (1828) mampu mengubah garam anorganik,
ammonium sianat, menjadi senyawa organik yaitu urea yang
sebelumnya telah ditemukan dalam urin manusia.
NH4 OCN C
O
H2N NH2
Atom terpenting yang dipelajari dalam kimia organik adalah
atom karbon. Meskipun demikian, atom lainnya juga dipelajari seperti
hidrogen, nitrogen, oksigen, fosfor, sulfur, dan atom lainnya. Akan
tetapi mengapa atom karbon sangat spesial? Atom karbon merupakan
termasuk dalam golongan 4A, karbon memiliki empat elektron valensi
yang dapat digunakan untuk membentuk empat ikatan kovalen. Di
dalam tabel periodik, atom karbon menduduki posisi tengah dalam
kolom periodenya. Atom di sebelah kiri karbon memiliki
kecenderungan memberikan elektron sedangkan di sebelah kanannya
memiliki kecenderungan menarik elektron.
14 St. Layli Prasojo, S.Farm., Apt.
Atom karbon dapat berikatan satu dengan lainnya membentuk
rantai panjang atau cincin. Karbon, sebagai elemen tunggal mampu
membentuk bermacam senyawa, dari yang sederhana seperti metana,
hingga senyawa yang sangat komplek misalnya DNA yang terdiri dari
sepuluh hingga jutaan atom karbon.
Jadi, senyawa karbon tidak hanya diperoleh dari organisme
hidup saja. Kimiawan modern saat ini sudah mampu menyintesis
senyawa karbon di dalam laboratorium. Contohnya: obat, pewarna,
polimer, pengawet makanan, pestisida, dan lain-lain. Saat ini, kimia
organik didefinisikan sebagai senyawa yang mengandung atom
karbon.