Lemak

(Pencernaan,Absorpsi dan Metaboisme)

Oleh : Suyatno, Ir. M.Kes

(Bagian Gizi FKM UNDIP Semarang)

Contact: Hp. 08122815730 Blog : suyatno.blog.undip.ac.id E-mail: suyatno_undip@yahoo.com

Lipids Intake
The most abundant dietary lipids, triglycerides, are found in both animal and plant foods Essential fatty acids linoleic and linolenic acid, found in most vegetables, must be ingested Dietary fats consist mainly of triglycerides, which can be split into glycerol and fatty acids. In many developing countries dietary fats make up a smaller part of total energy intake (often only 8 or 10 percent) In most industrialized countries the proportion of fat intake is much higher. For example: In the United States average of 36 percent of total energy is derived from fat.

Lipids Functional
Fats in the body are divided into two groups:
storage fat: provides a reserve storehouse of fuel for the body structural fat : part of the essential structure of the cells, occurring in cell membranes, mitochondria and intracellular organelles.

Klasifikasi Lemak
Terdiri:
Acyl-lipids: mengandung kelompok asam lemak sbg bagian non-polar Isoprenoids: terdiri 5 unit karbon isoprene

Lipid Subclasses

Fungsi utama Acyl-lipids:

komponen membran simpanan fat dan minyak menjaga kelembaban molekul signal (prostaglandin) Sphingomyelins : komponen membran
(cont. dlm lapisan mylein syaraf)

Phospholipids Triacylglycerols Waxes Eicosanoids

: : : :

Glycospingolipids: sell pengenal (antigen gol darah ABO)

Function Utama kelompok isoprenoid:

Steroids (sterols): Lipid Vitamins : Carotenoids : Chlorophyll : komponen membran, hormon Vitamin A, E, K pigmen kelengkapan fotosintesis pigmen penangkap energi sinar matahari : pembawa elektron yg larut lemak : menthol

Plastoquinone/ ubiquinone Essential oils

Phospholipids

Phospholipids are built on glycerol back bone. Two fatty acid groups are attached through ester linkages to carbons one and two of glycerol. Unsaturated fatty acid often attached to carbon 2 A phosphate group is attached to carbon three A polar head group is attached to the phosphate (designated as X in figure)

H2C

H C O C C2

CH2 O O C C2 C3 C3 C4 O

Triacylglycerols (TAG) (=Triglycerida) Fats and oils

Impt source of metabolic fuels Because more reduced than carbos, oxidation of TAG yields more energy (16 kJ/g carbo vs. 37 kJ/g TAG) Americans obtain between 20 and 30% of their calories from fats and oils. 70% of these calories come from vegetable oils Insulation subcutaneous fat is an important thermo insulator for marine mammals

O C1

C2 C3 C4 C4 C5 C6 C6 C7 C8 C8 C9 C10 C11 C9 C10 C7 C5

C5 C6 C7 C8 C9 C10 C11 C12 C13 C14 C15 C16 C17 C18

C12 C13 C14 C15 C16 C17 C18

C11 C12 C13 C14 C15 C16 C17 C18

Olestra
Olestra is sucrose with fatty acids esterified to OH groups digestive enzymes cannot cleave fatty acid groups from sucrose backbone Problem with Olestra is that it leaches fat soluble vitamins from the body

isoprenoids
Isoprenoids are derived from the condensation of 5 carbon isoprene units Can combine head to head or head to tail Form molecules of 2 to >20 isoprene units Form large array of different structures

Terpenes

Steroids
Based on a core structure consisting of three 6membered rings and one 5-membered ring, all fused together Triterpenes 30 carbons Cholesterol is the most common steroid in animals and precursor for all other steroids in animals Steroid hormones serve many functions in animals - including salt balance, metabolic function and sexual function

cholesterol
Cholesterol impt membrane component Function: stabilizes membranes and is a precursor of bile salts and steroid hormones Only synthesized by animals Accumulates in lipid deposits on walls of blood vessels plaques Plaque formation linked to cardiovascular disease

Cholesterol
Is the structural basis of bile salts, steroid hormones, and vitamin D Makes up part of the hedgehog molecule that directs embryonic development Is transported to and from tissues via lipoproteins

Steroids

Many steroids are derived from cholesterol

Asam Lemak (Fatty acids)

18:0 Saturated chains pack tightly and form more rigid, organized aggregates Unsaturated chains bend and pack in a less ordered way, with greater potential for motion 18:1 18:3

70o

13o

-17o

Konfigurasi Asam Lemak

Bag polar : karboksil Bag non-polar: rantai hidrokarbon Variasi struktuk (>100 tipe):
Beda dlm panjang rantai Beda dalam derajat ketidakjenuhan (unsaturation) Beda dalam posisi ikatan rangkap

Penamaan Asam Lemak

Menggambarkan: Jumlah karbon Jumlah ikatan rangkap Posisi ikatan rangkap dalam rantai karbon.
O C1 HO C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 C13 C14 C15 C16 C17 C18

C18:1 9 = asam oleat, asam lemak 18 karbon dengan satu ikatan rangkap pada karbon ke 9 dihitung dari atom karbon karboksil (antara karbon ke 9 and 10)

Penamaan Asam Lemak

Notasi Omega (): hitungan karbon dari akhir rantai hidrokarbon. Linolenate = 18:3 9,12,15 and 18:33,6,9 or 18:3(-3)
O C1 HO C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 C13 C14 C H15 C16 C17 C18

Linoleate: 18:26,9 or 18:2(-6) Oleat : 18:19 or 18:1(-9)

Asam Lemak Esensial:

Tubuh manusia hanya dapat mensintesis ikatanikatan rangkap mulai dari atom no 9 dari ujung omega Sel tubuh manusia tidak memiliki kemampuan untuk membentuk ikatan rangkap di posisi -3 dan -6. Asam lemak linoleat dan asam -linolenat tidak dapat diproduksi oleh tubuh. Kekurangan asam lemak esensial dapat menyebabkan:
terjadinya retardasi pertumbuhan, rambut menjadi kasar, penurunan kemampuan penyembuhan oleh tubuh (akibat kekurangan asam linolenat) dan gangguan penglihatan (akibat kekurangan asam asam linolenat).

Jenis Lemak Esensial:

Kelompok Omega-3(3): Linolenate = 18:33,6,9 or 18:3(-3) Turunannya: Eicosapentaenoat/EPA = 20:5 (-3) Docosahexanoat/DHA = 22:6 (-3) Kelompok Omega-6(6): Linoleate = 18:26,9 or 18:2(-6) Turunannya: Arachidonate = 20:4 (-6)

Asam Lemak Jenuh

common name 12:0 14:0 16:0 18:0 20:0 22:0 24:0 laurate myristate palmitate stearate arachidate behenate lignocerate IUPAC name dodeconoate tetradeconoate hexadeconoate octadeconoate eicosanoate docosanoate tetracosanate melting point (Co) 44 52 63 70 75 81 84

Asam Lemak Jenuh

common name 16:0 16:1 9 18:0 18:1 9 18:2 9,12 18:3 9,12,15 20:0 20:4 5,8,11,14 palmitate palmitoleate stearate oleate linoleate linolenate arachidate arachindonate IUPAC name hexadeconoate cis-9-hexadeconoate octadeconoate cis-9- octadeconoate cis-9,12- octadeconoate cis-9,12,15- octadeconoate eicosanoate cis- 5,8,11,14-eicosatetraenoate melting point (Co) 63 -0.5 70 13 -9 -17 75 -49

Pencernaan & Absorpsi Lemak

This action, the digestion or breakdown of fats, is achieved in the human intestine by enzymes known as lipases, which are present primarily in the pancreatic and intestinal secretions. Garam empedu (Bile salts) from the liver emulsify the fatty acids to make them more soluble in water and hence more easily absorbed.

Proses Pencernaan Lipida

Saluran Pencernaan
1. Mulut 2. Esofagus 3. Lambung

Proses Pencernaan
Bercampur dengan kelenjar ludah yang mengandung enzim lipase lingual Tidak ada pencernaan Lipase lingual memulai hidrolisis terbatas: trigliserida menjadi digliserida dan asam lemak Lemak susu lebih banyak dihidrolisis Lipase lambung menghidrolisis lemak dalam jumlah terbatas Bahan empedu mengemulsi lemak. Lipase dari pangkreas dan dinding usus halus menghidrolisis lemak dalam bentuk emulsi menjadi digliserida, monogliserida, asam lemak dan gliserol Fosfolipase dari pankreas menghidrolisis fosfolipid menjadi asam lemak dan lisofosfogliserida. Kolesterol esterase dari pankreas menghidrolisis ester kolesterol Sisa lemak dan kolesterol terkurung dlm serat makan dan dikeluarkan melalui feses

4. Usus Halus

5. Usus Besar

Digestion and absorption of lipids is in small intestine

The role of bile salt is: to stabilize the lipase (a little inhibit) to emulsify the droplets to help to form mixed micelles Colipase : small protein, keep lipase effectively attach to the substrate droplets. Micelles contain: free fatty acids mono-, di-acylglycerols small amount of TAG bile salts phospholipids fat-soluble vitamins.

Dalam Kantong Empedu, Empedu disimpan

Dalam hati, Kolesterol

Dalam usus halus, Empedu mengemulsi Lemak

empedu

Empedu diabsorbsi kembali ke dalam darah

Empedu dibuang melalui feses Menyebabkan warna feses

Gambar. Sirkulasi entero hepatik empedu

Absorpsi dan Transportasi Lipid

Absorpsi terjadi di jejenum Asam lemak rantai pendek dan menengah diabsorpsi langsung dalam vena porta dan dibawa ke hati untuk dioksidasi Kilomikron: lipoprotein pengangkut lipid (terutama trigliserida) dari saluran cerna ke dalam tubuh

Absopsi lipid ke dalam darah

Hasil Pencernaan Lipid
Gliserol Asam lemak rantai pendek (C4-6) Asam lemak rantai menengah (C8-10) Asam lemak rantai panjang Monogliserida Trigliserida Kolesterol fosfolipida

Absorpsi
Diserap langsung ke dalam darah

Diubah menjadi trigliserida di dalam selsel usus halus Membentuk kilomikron, masuk ke dalam limfe kemudian ke dalam darah

VLDL
Lipid menuju jaringan tubuh melalui lipoprotein lipase Sisa VLDL (IDL)

Usus Halus

kilomikron

Lipid menuju sel tubuh melalui lipoprotein lipase

Hati

Sisa Kilomikron

HDL mentransfer

LDL

HDL

kolesterol dari sel tubuh ke lipoprotein lain untuk digunakan

LDL ditarik oleh sel tubuh dengan reseptor apolipoprotein -100

LDL ditarik oleh jalur perusak (dlm pembuluh darah)

Dari bermacam sumber

Lipoproteins
High levels of HDL are thought to protect against heart attack High levels of LDL, especially lipoprotein (a), increase the risk of heart attack

 Lipoproteins are classified as:

HDLs high-density lipoproteins have more protein content LDLs low-density lipoproteins have a considerable cholesterol component VLDLs very low density lipoproteins are mostly triglycerides

Lipoprotein yang berperan dlm transport lemak

Kilomikron: mengandung paling banyak trigliserida dan paling sedikit protein sehingga mempunyai densitas paling rendah VLDL: terdiri atas kurang lebih separuh trigliserida, sehingga mempunyai densitas rendah LDL: terdiri atas kurang lebih separuh kolesterol, sehingga berpengaruh terhadap lebih 20 penyakit jantung koroner HDL: terdiri atas kurang lebih separuh lipoprotein, sehingga mempunyai densitas tinggi

Lipoprotein

LDL dan HDL

LDL penting sebagai pengontrol kolesterol LDL yang melalui jalur sel-sel perusak (scavenger pathway) akan teroksidasi dan tidak bisa masuk lagi ke pembuluh darah Kolesterol dalam LDL akhirnya menumpuk pada dinding pembuluh darah membentuk plak (plaque) Plak bercampur dengan protein dan ditutup sel otot dan kalsium menjadi aterosklerosis HDL mengambil kolesterol dan fosfolipid yang ada dalam pembuluh darah dan menyerahkan ke lipoprotein lain utk dibawa ke hati

Simpanan lemak
Simpanan lemak dalam tubuh di dalam sel lemak dalam jaringan adipos. Sel-sel adipos mempunyai enzim khusus pada permukaannya, yaitu lipoprotein lipase (LPL) yang dapat melepas trigliserida dan lipoprotein, menghidrolisisnya dan meneruskan hasil hidrolisis ke dalam sel. Di dalam sel terdapat enzim lain yang merakit kembali bahan-bahan hasil hidrolisis menjadi trigliserida untuk disimpan sbg cadangan energi. Sel-sel adipos menyimpan lemak bilamana kilomikron dan VLDL yang mengandung lemak melewati sel-sel tersebut.

Simpanan lemak

Lipid Metabolism

Lipid Metabolism
Most products of fat metabolism are transported in lymph as chylomicrons Lipids in chylomicrons are hydrolyzed by plasma enzymes and absorbed by cells Only neutral fats are routinely oxidized for energy Catabolism of fats involves two separate pathways
Glycerol pathway Fatty acids pathway

Lipid Metabolism
Glycerol is converted to glyceraldehyde phosphate
Glyceraldehyde is ultimately converted into acetyl CoA Acetyl CoA enters the Krebs cycle

Fatty acids undergo beta oxidation which produces:

Two-carbon acetic acid fragments, which enter the Krebs cycle Reduced coenzymes, which enter the electron transport chain

Lipid Metabolism

Lipogenesis and Lipolysis

Excess dietary glycerol and fatty acids undergo lipogenesis to form triglycerides Glucose is easily converted into fat since acetyl CoA is:
An intermediate in glucose catabolism The starting molecule for the synthesis of fatty acids

Lipogenesis and Lipolysis

Lipolysis, the breakdown of stored fat, is essentially lipogenesis in reverse Oxaloacetic acid is necessary for the complete oxidation of fat
Without it, acetyl CoA is converted into ketones (ketogenesis)

lipogenesis

lipogenesis

lipolysis

Lipogenesis and Lipolysis

Lipogenesis and Lipolysis

Supported Enzyme

(PUFA)

 Phospholipids are important components of myelin and cell membranes The liver:
Synthesizes lipoproteins for transport of cholesterol and fats Makes tissue factor, a clotting factor Synthesizes cholesterol for acetyl CoA Uses cholesterol to form bile salts

Lipid Metabolism: Synthesis of Structural Materials

Certain endocrine organs use cholesterol to synthesize steroid hormones

Lipid Metabolism
Digestion - Hydrolysis Reaction

Lipid Metabolism

Lipid Metabolism

Fatty Acid Oxidation

Initial Step: Requires an ATP to synthesize acetyl CoA with the fatty acid.

Beta Oxidation

Beta Oxidation

Beta Oxidation

Beta Oxidation

Beta Oxidation

Beta Oxidation

Beta Oxidation

Palmitic Acid Review

Palmitic Acid -ATP Synthesis

Palmitic Acid is C-16 Initiating Step - requires 1 ATP (text says 2) Step 1 - FAD into e.t.c. = 2 ATP Step 3 - NAD+ into e.t.c. = 3 ATP Total ATP per turn of spiral = 5 ATP Example with Palmitic Acid = 16 carbons = 8 acetyl groups Number of turns of fatty acid spiral = 8-1 = 7 turns ATP from fatty acid spiral = 7 turns and 5 per turn = 35 ATP. NET ATP from Fatty Acid Spiral = 35 - 1 = 34 ATP

Palmitic Acid (C-16) -ATP Synthesis

NET ATP - Fatty Acid Spiral = 35 - 1 = 34 ATP
Review ATP - Citric Acid Cycle start with Acetyl CoA Step ATP produced 7 visible ATP 1 Step 4 (NAD+ to E.T.C.) 3 Step 6 (NAD+ to E.T.C.) 3 Step10 (NAD+ to E.T.C.) 3 Step 8 (FAD to E.T.C.) 2 NET 12 ATP per turn C.A.C. 8 Acetyl CoA = 8 turns C.A.C. 8 turns x 12 ATP/C.A.C. = 96 ATP GRAND TOTAL 130 ATP

Acetyl CoA

Ketone Bodies

Ketone Bodies

Lipogenesis