METABOLISME ENERGI DAN ZAT GIZI MAKRO PERTEMUAN 8

Presentasi berjudul: "METABOLISME ENERGI DAN ZAT GIZI MAKRO PERTEMUAN 8"— Transcript presentasi:

1 METABOLISME ENERGI DAN ZAT GIZI MAKRO PERTEMUAN 8
HENDRA WIJAYA-DUDUNG ANGKASA PROGRAM STUDI ILMU GIZI-FIKES

2 VISI DAN MISI UNIVERSITAS ESA UNGGUL

3 KEMAMPUAN AKHIR YANG DIHARAPKAN
Mahasiswa dapat menjelaskan biosintesis asam lemak, trigliserida, kolesterol dan lipoprotein

4 BIOSYNTHESIS OF FATTY ACIDS Hendra Wijaya Esa unggul University

5 TRANSPORT OF ACETYL-COA INTO THE CYTOSOL

6 TRANSPORT OF ACETYL-COA INTO THE CYTOSOL
Acetyl-CoA generated in the mitochondrion Mitochondrial membrane is impermeable to acetyl-CoA Acetyl-CoA enters the cytosol in the form of citrate Processing of malate to pyruvate generates NADPH for fatty acid biosynthesis

7 OVERVIEW OF FATTY ACID SYNTHESIS

8 SYNTHESIS OF FATTY ACID
MOVIE

9 Acetyl-CoA Carboxylase reaction

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11 Acetyl-CoA Carboxylase reaction
Irreversible reaction that is the committed step in fatty acid synthesis Biotin-dependent Mechanism similar to that of pyruvate carboxylase Subject to allosteric and hormonal control Stimulated by citrate, inhibited by long-chain fatty acids Phosphorylation, which inhibits enzyme activity, is promoted by glucagon and reversed by insulin

12 Intermediates in Fatty Acid Synthesis are Linked to Acyl Carrier Protein (ACP)

13 REACTION SEQUENCE FOR FATTY ACID BIOSYNTHESIS
Intermediates attached to the sulfhydryl terminus of a phosphopantetheine group Phosphopantetheine linked to Ser hydroxyl of ACP, while attached to AMP in CoA ACP can be considered a big CoA molecule Individual enzymes in bacteria, enzyme complex in eukaryotes Condensation of malonyl-CoA and acetyl-CoA driven by decarboxylation Stereochemistry and reducing agent are different between synthesis and degradation In subsequent round of elongation, butyryl thioester condenses with malonyl-ACP after transfer to condensing enzyme Elongation cycles continue until palmitoyl(C16)-ACP is formed, which is hydrolyzed to give palmitate and ACP

14 STOICHIOMETRY OF FATTY ACID BIOSYNTHESIS
Stoichiometry of palmitate synthesis: Acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14H palmitate + 7CO2 + 14NADP+ + 8CoA + 6H2O Malonyl-CoA synthesis: 7 Acetyl-CoA + 7CO2 + 7ATP 7 malonyl-CoA + 7ADP + 7Pi + 7H+ Overall stoichiometry of palmitate synthesis: 8 Acetyl-CoA + 14 NADPH + 7ATP + 7H+ palmitate + 14NADP+ + 8CoA + 6H2O + 7ADP + 7Pi

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16 FATTY ACID ELONGATION In eukaryotes, elongation occurs in both mitochondria and the endoplasmic reticulum (ER), but the ER system has much higher activity Reactions occur on separate enzymes rather than in a complex Fatty acid is elongated as its CoA derivative Two carbon units are added sequentially the carboxyl end of both saturated and unsaturated fatty acids Malonyl-CoA is again the two-carbon donor

17 FATTY ACID DESATURATION
Double bonds are introduced into long-chain acyl-CoAs through an electron-transfer process coupled to the reduction of molecular oxygen Reaction catalyzed by a complex of membrane-bound enzymes Double bonds inserted such that the new double bond is three carbons closer to the CoA group, and never beyond the C9 position

18 ESSENTIAL FATTY ACID The formation of D12 and D15 double bonds is not possible in animals Animals cannot synthesize linoleic acid (18:2D9,12), linolenic acid (18:3D9,12,15), or arachidonic acid (20:4 D5,8,11,14), which are used in the synthesis of eicosanoid hormones Prostaglandins Leukotrienes These are called essential fatty acids because they are essential lipid components that must be provided in the diet

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22 BIOSYNTHESIS OF TRIACYLGLYCEROL

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24 TRIACYLGLYCEROL (TG) SYNTHESIS
Generally synthesized from glycerol 3-phosphate, which is produced by the reduction of dihydroxyacetone phosphate (DHAP) Acylations performed with acyl-CoA and acyltransferases Fatty acyl chain at C1 is usually saturated, fatty acyl chain at C2 is usually unsaturated TG and phospholipid pathways generally diverge at phosphatidic acid and diacylglycerol Diacylglycerol formed by phosphatase Acyltransferase forms TG

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26 CONFORMATIONAL MODEL OF (A) PHOSPHOLIPID PHOSPHATIDYLCHOLINE AND (B) TRIACYLGLYCEROL

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28 GLYCEROPHOSPHOLIPID

29 GLYCEROPHOSPHOLIPIDS: Membrane
Lesitin C1 substituents mostly saturated fatty acids, C2 substituents mostly unsaturated fatty acids PE, PG, and CL found in bacteria, eukaryotes contain all six Phospholipases serve as digestive enzymes and as generators of signal molecules

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31 CTP: Citidene Tryphosphate

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33 Biosynthesis Of PhospatidylserineI: CDP-Diacylglycerol Pathway
Sytosin CTP: Citidene Tryphosphate

34 Biosynthesis Of Phospatidylcholine: CDP-Choline & CDP-ethanolamine

35 PHOSPHOLIPID SYNTHESIS

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38 KETON BODIES

39 9/15/2018 Metabolisme Lipida

40 KETONE BODIES Acetyl-CoA from fatty acid oxidation enters the citric acid cycle when fat and carbohydrate breakdown are balanced Entry depends on oxaloacetate Oxaloacetate consumed to form glucose by gluconeogenesis in fasting, diabetes, and starvation In the absence of oxaloacetate, acetyl-CoA is converted to acetoacetate or D-b-hydroxybutyrate through ketogenesis Acetone is formed by the non-enzymatic decarboxylation of acetoacetate Ketone bodies are important fuel molecules OVERVIEW

41 Formation of keton bodies from acytil-CoA
Initial condensation Ester condensation to form HMG-CoA (also precursor in cholesterol biosynthesis) Acetoacetate and acetyl-CoA formed in a mechanism similar to the reverse of the citrate synthase reaction

42 Metabolic Conversion of Ketone Bodies to Acetyl-CoA S
Acetoacetate reduced to hydroxybutyrate in an NADH-dependent reaction Acetoacetyl-CoA can be cleaved by thiolase to give 2 acyl-CoA The liver can supply acetoacetate to other tissues

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47 Cholesterol

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53 SPHINGOLIPIDS

54 SPHINGOLIPIDS

55 SPHINGOLIPIDS

56 SPHINGOLIPIDS Backbone is ceramide rather than glycerol
Most sphingolipids contain carbohydrates as their head group Sphingolipids play important roles in nervous tissue Sphingomyelin is an important component of the myelin sheath Gangliosides constitute 6% of the lipids in gray matter

57 SYNTHESIS OF CERAMIDA

58 Toy-Sachs Disease: A Disorder of Ganglioside Breakdown
Gangliosides are degraded inside lysosomes by the sequential removal of terminal sugars In Tay-Sachs disease, ganglioside GM2 accumulates because hexosaminidase activity is absent This ganglioside interferes with neuronal function Genetic recessive disease

59 MEMBRANE LIPIDS Have a hydrophilic and hydrophobic component
1,2-diacylglycerol or N-acetylsphingosine (ceramide) linked to a polar head group Hydrophobic acyl chains Form bilayered membranes in aqueous media Membranes are noncovalent, fluid assemblies Membrane lipids synthesized predominantly on the cytoplasmic face of the ER, then transported in vesicles to their destinations

60 β -OXIDATION vs BIOSYNTHESIS

61 FATTY ACID BIOSYNTHESIS VS β-OXIDATION

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63 Hendra Wijaya Esa unggul university
Atherosclerosis Hendra Wijaya Esa unggul university 9/15/2018 Metabolisme Lipida

64 ATHEROSCLEROSIS Aterosklerosis : proses patologis yang
menyerang pembuluh darah arteri berukuran sedang dan besar Atherosclerosis (bahasa Yunani) => athero = subur; scleros = keras  bertalian erat dengan penyimpangan metabolisme lemak dan kolesterol  merupakan penyebab timbulnya penyakit kardiovaskuler DISLIPIDEMIA :  kolesterol total (> 200 mg/dl)  LDL (> 130 mg/dl)  trigliserida (> 200 mg/dl)  HDL (< 35 mg/dl) 9/15/2018 Metabolisme Lipida

65 ARTERI TREE AND ATHEROSCLEROSIS

66 ATHEROSCLEROSIS A : pembentukan fatty streak
B : Progresi lesi lebih lanjut C : Lesi lanjutan berupa pembentukan plaque dan thrombus 9/15/2018 Metabolisme Lipida

67 ATHEROSCLEROSIS 1 2 3 4 9/15/2018 Metabolisme Lipida

68 ATHEROSCLEROSIS

69 MEKANISME MOLEKULAR

70 FAKTOR RESIKO Makan & Minum Berlebihan Obesitas Gaya Hidup Santai
Diabetes Aterosklerosis Merokok Konsumsi Garam Dapur Tinggi Hipertensi Penyakit Kardio- Konsumsi Lemak Total Tinggi vaskuler Konsumsi Lemak Jenuh Tinggi Rasio Konsumsi Lemak Tidak Jenuh/Jenuh Rendah Konsumsi Kolesterol Tinggi Kadar Kolesterol Darah Meningkat 9/15/2018 Metabolisme Lipida

71 EFFECTS OF DIETARY INTAKE
Cholesterol that accumulates in arteries is manufactured largely from fragments derived from saturated fat. Saturated fatty acids elevate blood cholesterol and are the main determinants of blood cholesterol Saturated fatty acids elevated LDL PUFA and MUFA lower blood cholesterol Dietary cholesterol elevates cholesterol Very low fat diets  lower all types of lipoproteins, may raise triglycerides High sugar diet, High alcohol intake may raise triglycerides 9/15/2018 Metabolisme Lipida

72 Penyakit Jantung Koroner
Telah lama diketahui bahwa konsumsi asam lemak tidak jenuh yang tinggi cenderung menurunkan kadar kolesterol plasma. Konsumsi minyak kedelai yang cukup (10,6 % dari total energi) menurunkan kadar kolesterol total dan kolesterol-LDL pada manusia (Pakpaenkitvatana et al, 1989) Efek merendahkan kadar kolesterol darah oleh asam lemak tidak jenuh (ALTJ) disebabkan oleh mekanisme produksi VLDL. Hipotesis: ALTJ menurunkan sintesis VLDL, dan sebagai akibatnya produksi LDL juga berkurang. Selanjutnya ALTJ yang tidak membentuk formasi trigliserida pada VLDL akan dioksidasi sebagai sumber energi dan ketone bodies yang terbentuk akhirnya akan dikeluarkan melalui urine dan saluran pernafasan, atau dikonversi menjadi glukosa (Beynen dan Katan (1985) . 9/15/2018 Metabolisme Lipida

73 REKOMENDASI THE AMERICAN HEART ASSOCIATION :
 Total calories intake : adjusted to maintain a healthy body weight  Total fat intake : max. 30 % of total calories  Saturated fat : 7-10 % of total calories  Polyunsaturated fat : up to 10 % of total calories  Monounsaturated fat : up to 15 % of total calories  Cholesterol intake : less than 200 mg per day  Sodium intake : less than 2400 mg per day  Carbohydrate intake : % of total calories (CHO complex) 9/15/2018 Metabolisme Lipida

74 Prostaglandin : ● platelet membentuk thromboxane A2 (TXA2)
 agregasi platelet, saluran darah mengecil ● saluran darah dan sel-sel lain membentuk prostacyclin (PGI2)  mencegah agregasi platelet, saluran darah melebar ASAM LEMAK OMEGA-3 dapat mencegah terbentuknya TXA2 dan menstimulir pembentukan PGI2 9/15/2018 Metabolisme Lipida

75 Eicosapentaenoic Acid (EPA) Docosahexaenoic Acid (DHA)
Linolenic Acid omega-3 Linoleic Acid omega-6 Eicosapentaenoic Acid (EPA) Docosahexaenoic Acid (DHA) Arachidonic Acid Eicosanoids Regulate BP Regulate Blood Clotting (Linoleic-Increases Clotting) (Linolenic Decreases Clotting) Regulate Inflammatory Reactions 9/15/2018 Metabolisme Lipida

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77 TERIMA KASIH