Metabolisme Lemak.

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1 Metabolisme Lemak

2 Lipid The term lipid refers to a structurally diverse group of molecules that are preferentially soluble in a nonaqueous solvent such as chloroform Lipids include a wide variety of fatty acid‐derived compounds, as well as many pigments and secondary compounds that are metabolically unrelated to fatty acid metabolism. As the major components of biological membranes, they form a hydrophobic barrier that is critical to life Fatty acids are substantially more reduced organic molecules than carbohydrates, fatty acid oxidation has a higher potential for producing energy Pelarut: larutan organik non polar. Fungsi lipid: proses metabolisme, melindungi organ, penghasil panas, sumber asam lemak esensial, pelarut vitamin. Sumber lipid dari luar dan diproduksi sendiri di hati.

3 Lipid sederhana merupakan lemak yang disusun oleh trigliserida, yaitu tiga asam lemak dan satu gliserol Hidrolisis : asam lemak + alkohol a. Lemak/trigliserida Hidrolisis : asam lemak + gliserol b. lilin/wax  Hidrolisis : alkohol rantai panjang + asam lemak rantai panjang 2. Lipid majemuk merupakan lemak yang terdiri dari asam lemak dan gugus tambahan lain selain lemak Hidrolisis : asam lemak + alkohol + senyawa lain. Contoh : - fosfolipid : asam lemak + alkohol + fosfat. - glikolipid : asam lemak + alkohol + karbohidrat 3. Turunan lipid merupakan senyawa lemak yang dihasilkan dari proses hidrolisis lipid. Contoh : kolesterol, steroid

4 Lipid berdasarkan struktur
1. lipid dengan rantai hidrokarbon terbuka ex: asam lemak, TAG, spingolipid, fosfolipid, glikolipid 2. Lipid dengan rantai hidrokarbon tertutup/siklis Ex: steroid (kolesterol)  asam lemak adalah asam karboksilat dengan rantai alifatik panjang, baik jenuh maupun tak jenuh. Hampir semua asam lemak alami memiliki rantai tak bercabang dengan jumlah atom karbon genap, mulai dari 4 sampai 28.[1]Asam lemak biasanya diturunkan dari trigliserida atau fosfolipida. asam lemak. Asam lemak yang terdapat di alam adalah asam palmitat (C15H31COOH), asam stearat (C17H35COOH), asam oleat (C17H33COOH), dan asam linoleat (C17H29COOH).

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6 Lipid berdasarkan fungsi
Storage Lipid Structural Lipid (penyusun membran) Fungsional Lipid (signal, kofaktor dan pigment)

7 Lipid berdasarkan struktur
Lemak Jenuh (saturated fat) Lemak tak jenuh (unsaturated fat) Lemak Jenuh (saturated fat), yaitu struktur lemak dengan hidrokarbon ikatan. Lemak jenuh kebanyakan berasal dari hewan, seperti daging, susu murni, dll. Ex: asam laurat, asam palmitat, asam stearat. Lemak tak jenuh (unsaturated fat), yaitu struktur lemak dengan hidrokarbon dengan satu atau lebih ikatan rangkap (ganda). Lemak tak jenuh kebanyakan berasal dari tumbuhan, contohnya lemak dari buah alpukat dan kacang-kacangan. e;: asam oleat, asam linoleat, asam linolenat.

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9 Lemak pada tumbuhan Membran chloroplast, in which the light reactions of photosynthesis take place, primarily contain galactolipids. Membranes external to plastids are composed mainly of mixtures of phospholipids. Triacylglycerols are largely hydrophobic and exist in an essentially anhydrous environment. Waxes that coat and protect plants from the environment are complex mixtures of longchain hydrocarbons, aldehydes, alcohols, acids, and estersderived almost entirely from fatty acids. Cutin layer of epidermal cells also is composed of oxygenated fatty acids esterified with one another to produce a tough, polyester skin.

10 Lipid Function in Plant

11 Perbandingan energi (ATP) yang dihasilkan oleh oksidasi karbohidrat dan asam lemak

12 Biosythesis dan metabolisme lemak terjadi di beberapa organel dalam sel

13 Fatty acids Fatty acids are carboxylic acids of highly reduced hydrocarbon chains The typical fatty acids found in the membranes of plants contain 16 or 18 carbons

14 Fatty Acids in Plants acid), is designated 16:0. The first value, 16, represents the number of carbon atoms. The second value, 0, indicates the number of double bonds. The monounsaturated 18‐carbon fatty acid, oleic acid (cis‐9‐octadecenoic acid), is designated 18:1Δ9. The Δ9 superscript designates the position of the single double bond, counting the carboxyl group as carbon atom number 1. Because the double bonds in fatty acids are almost exclusively cis isomers, usually no designation for the configuration of double bond is used unless it is a trans isomer, as in 16:1trans Δ3. As shown in the illustration of palmitic and linolenic acids, major saturated and unsaturated fatty acids in photosynthetic tissues, introduction of cis unsaturations creates bends in the acyl chain. Double bonds are usually separated by one carbon in the fatty acid chain (e.g., in the polyunsaturated α‐linolenic acid, 18:3Δ9,12,15). It is sometimes useful to designate the position of the double bonds relative to the terminal methyl group (the omega carbon). Thus, an omega‐3, or n‐3, fatty acid contains a double bond three carbons from the methyl end of the fatty acid (e.g., 18:3Δ9,12,15 is an omega‐3 fatty acid).

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16 Perkiraan distribusi penyusun sel pada daun tanaman Arabidopsis thaliana

17 Glycerolipid Consist of fatty acids esterified to derivatives of glycerol. Four principal types are found in plants: triacylglycerols, phospholipids, galactolipids, and a sulfolipid. Plants contain sphingolipids, which can be major components of the plasma membrane

18 Triacylglycerols (TGA)
Lipids are usually stored as triacylglycerols, three fatty acids esterified to glycerol Triacylglycerols and highly accumulated in in seeds and pollen serve as energy and carbon stores.

19 Phospholipids Phospholipids are the main component of cell membrane.
Synthesized by esterification of fatty acids to the two hydroxyl groups of sn‐glycerol 3‐phosphate to produce phosphatidic acid.

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22 Galactolipids Are localized in the plastid membranes
Galactosyl or sulfoquinovosyl group replaces the phosphoryl head group of the phospholipids Contain high concentrations of polyunsaturated fatty acids Photosynthetic tissue of some plants, α‐linolenic acid can constitute as much as 90% of the fatty acids in glycolipids

23 The basic structure of a glycerolipid is shown at the top
The basic structure of a glycerolipid is shown at the top. The C3 backbone (highlighted in dark yellow) is usually esterified to two fatty acids at the carbonslabeled sn‐1 and sn‐2. The modifications of the sn‐3 carbon can be described by the substituents X and Y, which correspond to the compounds shown in the lower part of the table. sn numbers refer to the stereochemical nomenclature system, which is, by convention, based on the structures of d‐ and l‐glyceraldehyde. The convention with respect to glycerol is that, in a Fisher projection of l‐glycerol (not shown), the central hydroxyl is shown to the left. By definition, the carbon above the sn‐2 carbon is the sn‐1 position and the position below is the sn‐3 position.

24 Sphingolipids Represent approximately 5% of the total membrane lipids
Make up as much as 26% of the mass of plasma membrane lipids Sphingolipids are not esters of glycerol, but rather consist of a long‐chain amino alcohol that forms an amide linkage to a fatty acid;

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26 Fatty Acid Biosynthesis
Reaksi sintetis asam lemak terjadi hanya di kloroplas daun serta di proplastid biji dan akar. FA yang disintesis adalah asam palmitat & asam oleat. Asetil CoA yang digunakan untuk membentuk lemak di kloroplas sering dihasilkan oleh piruvat dehidrogenase dengan menggunakan piruvat yang dibentuk pada glikolisis di sitosol. Sumber lain asetil CoA pada kloroplas berasal dari asetat bebas dari mikotondria. Asetat ini diserap oleh plastid dan diubah menjadi asetil CoA, untuk digunakan membentuk asam lemak dan lipid lainnya Asam lemak dibentuk oleh kondensasi berganda unit asetat dari asetil CoA.

27 Fatty Acid Biosynthesis
Acetyl‐CoA  substrat untuk synthesis FA Selama biosintesis FA, terjadi pengulangan reaksi penggabungan acetyl moieties dari acetyl‐CoA kedalam grup acyl karbon 16 atau 18. Enzim yang berperan meliputi: acetyl‐CoA carboxylase (ACCase) dan fatty acid synthase (FAS) FAS mengkatalisasi konversi acetyl‐CoA dan malonyl‐CoA menjadi FA 16:0 and 18:0 Pada reaksi sintesa asam lemak, enzim CoA dan protein pembawa asil (ACP) membentuk rantai asam lemak dengan menggabungkan secara bertahap satu gugus asetil turunan dari asetat dalam bentuk asetil CoA dengan sebanyak n gugus malonil turunan dari malonat dalam bentuk malonil CoA, Animals and yeast use a Type I FAS  lebih komplek dan large subunit yang masing2 mengkatalis reaksi yang berbeda. Plants and most bacteria have a Type II FAS, in which each enzyme activity resides on an individual protein that can be readily separated from the other activities participating in fatty acid synthesis. Type II FAS also includes ACP. The Type II FAS functions much like a metabolic pathway, whereas Type I FAS functions like a large protein complex (e.g., pyruvate dehydrogenase).

28 Acetyl-CoA merupakan seyawa sampingan terpenting di metabolisme sel
Acetyl‐CoA may be the most central intermediate in cellular metabolism, providing a link between many pathways. include glycolysis (via pyruvate dehydrogenase) and fatty acid oxidation. Acetyl‐CoA is the starting material for biosynthesis of fatty acids, several amino acids, flavonoids (via chalcone synthase), sterols, and many isoprenoid derivatives synthesized in the cytosol. During respiration, acetyl‐CoA is the source of carbon input into the citric acid cycle in the mitochondria. Despite this central role, acetyl‐CoA is not believed to cross membranes and must be produced in the compartment in which it is utilized.

29 Fatty Acid Biosynthesis
Fatty acid biosynthesis is initiated by the ATP‐dependent carboxylation of acetyl‐CoA to form malonyl‐CoA Next, the malonyl group is transferred to ACP Assembly of the fatty acid begins when a carbon–carbon bond forms between C‐1 of an acetate “primer” and C‐2 of the malonyl group on ACP to form cetoacetyl‐ACP, (which releases CO2). Subsequently, a sequence of three reactions—reduction, dehydration, and reduction again—leads to the formation of the fully reduced acyl‐ACP

30 Acyl-carrier protein (ACP)

31 Perbedaan komposisi gliserolipid pada masing-masing organ tanaman

32 Perbandingan komposisi lemak di kloroplast dan mitokondria
Phosphatidylcholines (PC)  phospholipids that incorporate choline (sejenis vitamin; water soluble) as a headgroup. They are a major component of biological membranes , such as egg yolk or soybeans,. They are also a member of the lecithin group of yellow-brownish fatty substances occurring in animal and plant tissues. Phosphatidylethanolamines  phospholipids found in biological membranes.[1]  It can mainly be found in the inner (cytoplasmic) leaflet of the lipid bilayer.[2] Cardiolipin  komponen inner mitochondrial membrane,. It can also be found in the membranes of most bacteria, In mammalian cells, but also in plant cells,  berfungsi untuk sintesis energi di mkitokondria Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant.[1] The general structure of phosphatidylglycerol consists of a L-glycerol 3-phosphate backbone ester-bonded to either saturated or unsaturated fatty acids on carbons 1 and 2. The head group substituent glycerol is bonded through a phosphomonoester. Phosphatidylinositol consists of a family of lipids as illustrated on the right, a class of the phosphatidylglycerides. In such molecules the isomer of the inositol group is assumed to be the myo- conformer unless otherwise stated. Inositol  prosessignal transduksi, cytoskleton, gene expression Monogalactosyldiacylglycerol The function of this unusual lipid with its lack of electrical charge and high degree of unsaturation is to provide a fluid environment in which the diffusional processes of photosynthetic electron transfer can occur and, maybe, to facilitate the optimal packing of large intrinsic proteins within the naturally occurring bilayer structure. MDGD dan DGDG  sebagai antiinflamantory and anti cancer karena bisa menangkap radikal bebeas seperti No.- DigalactosyldiacylglycerolThe plant galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) have been linked to the anti-inflammatory and cancer benefits of a green leafy vegetable diet in humans due to their ability to regulate the levels of free radicals like nitric oxide (No. Sulfolipids are a class of lipids which possess a sulfur-containing functional group.  nonphosphorous glycerolipid that is specifically associated with photosynthetic membranes of higher plants, mosses, ferns, algae, and most photosynthetic bacteria. The characteristic structural feature of sulfoquinovosyl diacylglycerol is the unique head group constituent sulfoquinovose, a derivative of glucose in which the 6-hydroxyl is replaced by a sulfonate group. 

33 Mutant yang mengakumulasikan lemak 18:0 menunjukkan kekerdilan
Morphology of the fab2 mutant of Arabidopsis. (A) The growth of the mutant (at right) at 22°C is strongly reduced. The mutant plant is small because its cells (B) compared to wild type (C) do not enlarge to the same extent. Growth at higher temperature partially suppresses the deleterious effects of the fab2 mutation (D) on growth and development. The mutant grown at 36°C more closely resembles the wild‐type control (E). The work with Arabidopsis mutants indicates plants require polyunsaturated lipids to maintain the photosynthetic machinery, but this is not true of cyanobacteria. Mutants of Synechocystis PCC6803 that lack polyunsaturated fatty acids can photosynthesize normally, except at low temperature.

34 Photosynthesis is impaired in plants that lack
polyunsaturated membrane lipids

35 Lipid composition affects
chilling sensitivity A: wild type B: mutant fad6  clorotic after 3 weeks at 5C C: mutn di suhu 2 C selama 1 minggu masih normal D: setelah 4 minggu di 2 C  menunjukkan simtom chlorosis dan petumbuhannya terhambat

36 Cold acclimation allows plants to survive
freezing

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38 Lipids are stored in oil body in the seed

39 In oilseeds, oil bodies are droplets of triacylglycerols surrounded by a monolayer of phospholipids, with the hydrophobic acyl moieties of the phospholipids interacting with the triacylglycerols and the hydrophilic head groups facing the cytosol. Oil bodies also contain major protein components called oleosins, Oleosins are lowmolecular‐mass proteins (15–25 kDa) that contain a sequence of 70–80 hydrophobic amino acids toward the middle of the protein. The sequence of this hydrophobic domain is conserved in oleosins from different plant species, but these proteins are not found in animals, bacteria, or fungi Oleosins are found only in oil bodies of seeds and pollen, both of which undergo dehydration during maturation

40 Synthesis of storage lipids
In seed tissues, 16:0‐ACP and 8:1Δ9‐ACP are hydrolyzed to free fatty acids by thioesterases in the plastid stroma and transferred through the plastid envelope by an unknown mechanism The free fatty acids are converted to acyl‐CoAs in the outer plastid envelope, forming the substrates for subsequent acyltransferase reactions. Newly produced 18:1Δ9‐CoA,18:0‐CoA, and 16:0‐CoA can be used for the synthesis of phosphatidylcholine and phosphatidic acid

41 Pembetukan oil body dan proses degradasinya

42 Mobilisasi lemak tersimpan saat perkecambahan biji
Pada sel tumbuhan sebagian besar asam lemak diubah menjadi gula (sucrose) dan diangkut untuk pertumbuhan kecambah

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44 Lintasan Biosintesis Asam Lemak
Bahan utama yg digunakan pd biosintesis as. Lemak → asetil CoA & malonil CoA → Malonil CoA disintesis dr asetil CoA dg penambahan CO2 oleh asetil CoA karboksilase Reaksi pertama pd biosintesis as. Lemak → pemindahan gugus asetil & gugus malonil dr CoA ke ACP dg katalis asetil-CoA; ACP transilase & malonil-CoA; ACP transilase Reaksi berikutnya → pengkondensasian gugus malonil membentuk asetoasetil-ACP dg melepaskan CO2

45 Lanjutan Tahapan selanjutnya → urutan reaksi2 yg merupakan siklus lintasan pembentukan & penambahan panjang rantai as. lemak reaksi reduksi dg katalis 3-ketoasil ACP reduktase reaksi dehidrasi dg katalis 3-hidroksi ACP dehidrase reaksi reduksi dg katalis enoil ACP reduktase → Hasil adl molekul as. lemak yg terikat dg ACP dg jml atom C sebanyak 4 Bila panjang rantai molekul as. lemak blm cukup → hasil sintesis ini kembali masuk siklus ‘kondensasi-reduksi-dehidrase-reduksi’ utk menambah panjang rantai as. lemak dg 2 atom C Hasil sintesis as. lemak dpt terikat dg ACP & CoA → CoA akan terhidrolisis & keluar bila as. lemak bergabung dg gliserol selama pembentukan lemak

46 Lintasan pembentukan as
Lintasan pembentukan as. lemak dr piruvat melalui tahapan pembentukan asetil CoA & malonil CoA pd plastid Pd reaksi pembentukan as. lemak dibutuhkan banyak energi → diperlukan 2NADPH & 1ATP utk tiap gugus asetil Kebutuhan energi ini di daun tersedia dr fotosintesis → shg pembentukan as. lemak pd kondisi terang berlangsung lebih cepat drpd kondisi gelap Pd kondisi gelap di proplastid biji & akar → NADPH tersedia dr lintasan respirasi pentosa fosfat, & ATP dr glikolisis piruvat yg merupakan senyawa asal dr asetil CoA

47 Lanjutan Sebagian besar as. lemak terbentuk di ER walaupun as. oleat & palmitat dibentuk di plastid As. lemak yg disintesis di proplastid biji & akar terutama adl as. palmitat & oleat Pd biji → as. lemak yg diproduksi dpt langsung diesterifikasi dg gliserol membentuk oleosom Kemungkinan lain → as. lemak diangkut balik ke proplastid utk membentuk oleosom As. lemak dpt diubah mjd fosfolipid di ER semua sel sebagai bahan utk pertumbuhan membran ER & membran sel lain Di ER pd daun → as. linoleat & linolenat yg disintesis diangkut ke kloroplas & ditimbun sbg lipid di membran tilakoid Plastid – organel sel yg bertangung jawab thd pembuatan energi