ENZIM DAN PROTEIN

Vilya Syafriana, M.Si.

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ENZIM SEBAGAI BAHAN OBAT

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 PENDAHULUAN

 Reaksi kimia yang terjadi di dalam sel mahluk hidup

dikontrol suatu katalis yang dikenal ENZIM.
 Enzim adalah suatu protein yang berperan sebagai
katalis: mempercepat reaksi, tanpa ikut bereaksi,
menurunkan energi yang digunakan.

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BAGAIMANA ENZIM BEKERJA
 Enzymes typically catalyze only one or a few similar
chemical reactions because they are specific in their
choice of substrates.
 This specificity is due to the active site of the enzyme,
which is shaped so that only a certain substrate molecule
will fit into it.

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 BAGIAN-BAGIAN ENZIM
 Enzim/Holoenzim terbagi 2 macam:
1. Protein (Apoenzim)
2. Non Protein (gugus prostetik): bagian non protein yang tidak
terpisahkan dari enzim. Bagian ini ada dalam keadaan enzim
aktif/tidak.
a) Koenzim: gugus yg ada pada enzim yang aktif, mis.NADPH,
NADH, FADH
b) Kofaktor: gugus yang diikat oleh enzim yang aktif, mis.Mg,
Zn, Fe, Cu, K, dsb.
 Holoenzim: enzim yang strukturnya sempurna juga aktif
mengkatalisis bersama-sama dgn koenzim & kofaktor. 7
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 FUNGSI ENZIM

specific characteristic features of enzyme are:

(1) Enzymes are reaction specific in that they act exclusively on
certain substances (known as ‘substrates’).
(2) Enzyme and its corresponding substrate or substrates invariably
give rise to an enzyme-substrate complex, which involves not
only physical shape but also chemical bonding.
(3) Enzyme helps in promoting the ‘creation of bonds’ either
between altogether separate substrates, or induces the cleavage
of bonds in a single substrate to result into the formation of the
product or products of reaction.
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(4) Metabolism: Numerous enzymes present in human body,
whereby each catalyzing one of the several reactions which
essentially occur as part of metabolism.
(5) Functionality: It has been duly observed that each enzyme acts
at an optimum temperature and a pH, at which it does function
most efficaciously.
For most human enzymes, these shall be particularly confined to
such factors as: pH of cells, body temperature, tissue fluid, and
blood.
(6) Impaired Activity: Impaired activity of enzymes may be caused
due to extremes of pH, temperature, dehydration, UV-radiation,
and the presence of heavy metals viz., Pb or Hg.
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(7) Specific Requirements: Certain enzymes specifically require the
dire presence of coenzymes (i.e., non protein molecules e.g.,
Vitamins) to enable them function properly; whereas, still others
require some critical minerals, such as: Fe, Cu, Zn).
(8) Proenzyme: It has been observed that certain enzymes are
obtained as proenzyme i.e., in an inactive form; and, therefore,
must be duly activated by appropriate means viz., inactive
pepsinogen is suitably converted to active pepsin by the help of
hydrochloric acid (HCl) present in the gastric juice.

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(9) Activity: Enzymes do possess a variety of vital and important
activities, such as:
(a) Digestive Enzymes: They are basically the ‘hydrolytic
enzymes’ which specifically catalyze the addition of water
molecules to relatively bigger food-molecules to help them split
into rather simpler chemical entities.
Quite often the very name of the enzyme explicitely indicates
the ‘substrate’ with addition of the suffix-ase.
Examples:
(i) Lipase—It splits fat (triglycerides) into the corresponding fatty
acids and glycerol respectively.
(ii) Peptidase—It splits peptides to the corresponding amino
acids. Exceptions: Certain enzymes e.g., pepsin and trypsin do
not usually end in –ase, because they were duly baptized much
before this method of nomenclature was actually instituted. 12
 (b) Enzymes for Synthesis Reactions: The enzymes for synthesis
reactions help to synthesize a host of biological products, such as:
glycogen, hormones, nucleic acids (DNA and RNA),
phospholipids for cell membranes, and proteins.
Examples: DNA Polymerase—is essentially required for DNA-
replication, that actually precedes mitosis.
(c) Energy Production: It also specifically requires a plethora of
enzymes.
Examples: Each and every step related to cell respiration needs
essentially a particular enzyme, for instance: cytochrome
transport system, glycolysis, and Krebs cycle.
(d) Deamination Reactions: The deamination reactions are usually
carried out by deaminases which critically remove the amino
moieties from the available pool of excessive amino acids so that
they may exclusively utilized for energy. 13
(10). Miscellaneous Activities of Enzymes: These categorically include
certain highly specific enzymes to perform a definite purpose in
vivo,
A few such typical examples are as given namely:
(a) Cessation of Long-chain Fatty Acids: Specific enzymes aid in the
splitting of longchain fatty acids into relatively smaller compounds
which in turn used up in the cell respiration mostly.
(b) Maintenance of Blood Pressure: Specific enzymes are usually
required for ‘blood clotting’, and also for the formation of
angiotensin II solely required to maintain and raise the blood
pressure.

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 SUMBER ENZIM

 The sources of enzymes that are viable commercially range from

animals, higher-plants, and microorganisms.
(a) Animal Enzymes e.g., lipases, rennets, tripsin etc.
(b) Higher-plant Enzymes e.g., amylases, papain, proteases, and
soybean lipoxygenase.
(c) Microorganisms e.g., Acetobacter lacti, Clostridium aceticum.

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 ENZIM BERDASARKAN SITUS BEKERJANYA:

 Endoenzymes [or Intracellular Enzymes]: berada di dalam sel.

Berperan dalam sintesis berbagai material di dalam sel,
penyimpanan cadangan makanan, dan sumber energy. Sebagai
contoh: isomerase, fosforilase, sintase.
 Exoenzymes [or Extracellular Enzymes]: enzim yang
disekresikan di luar sel. Berperan dalam penyerapan zat u tuk
masuk ke dalam sel. Mengubah molekul kompleks menjadi lebih
sederhana. Sebagai contoh: amilase, lipase, protease.
PENGGOLONGAN ENZIM BERDASARKAN CEIUB (THE
COMMISSION ON ENZYMES OF THE INTERNATIONAL
UNION OF BIOCHEMISTRY)

Enzim terbagi menjadi 6 Kelas:

1. Oksidoreduktase
2. Transferase
3. Hidrolase
4. Liase Jelaskan pengertian dari ke-6
golongan enzim tersebut dan
5. Isomerase berikan contoh!
6. Ligase
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ENZYMES OF PHARMACEUTICAL
RELEVANCE AND UTILITY

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Michel Vellard. (2003).The enzyme as drug: application of enzymes as
pharmaceuticals. Current Opinion in Biotechnology. Vol.14: 444–450
 ORAL AND INHALABLE ENZYME THERAPIES
 Penderita Congenital sucrase-
isomaltase deficiency (CSID)
diobati dengan sacrosidase,
yaitu beta-fructofuranoside
fructohydrolase yang berasal
dari Saccharomyces cerevisiae
yang dapat digunakan secara
oral.
 Pasien CSID tidak mampu
mencerna sukrosa.
 Obat tersebut akan
menghidrolisis sukrosa
sehingga pasien dapat
mencernanya.
 Phenylketonuria (PKU):
penyakit kelainan genetic
dimana pasien kekurangan
enzim fenilalanin hydrolase
(untuk mengubah fenilalanin
menjadi tirosin).
 Pengobatan oral PhenylaseTM,
sedang dikembangkan melalui
rekombinasi khamir
phenylalanine ammonia lyase
(PAL).
 PAL mampu mendegradasi
fenilalanin dalam saluran 24
gastrointestinal.
PROTEOLYTIC AND GLYCOLYTIC ENZYMES FOR
TREATING DAMAGED TISSUE
Debrase gel dressing:

•mengandung campuran enzim yang diekstraksi dari nanas. Digunakan untuk luka
bakar tebal sebagian atau penuh.

VibrilaseTM (recombinant vibriolysin):

•merupakan enzim proteolitik dari mikroorganisme laut Vibrio proteolyticus. Enzim

tersebut memiliki efikasi terhadap denaturasi protein pada kulit terbakar.

Chondroitinases:

•digunakan dalam patah tulang. Enzim ini menunjukkan kemampuan meregenerasi

saraf tulang belakang. Enzim ini bekerja dengan memindahkaan kondroitin sulfat yang
terakumulasi sehingga menghalangi pertumbuhan akkson.

Hyaluronidase:
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•memiliki sifat hidrolitik yang sama terhadap kondroitin sulfat, sehingga digunakan
untuk regenerasi saraf yang rusak.
ENZYMES FOR THE TREATMENT OF INFECTIOUS
DISEASES

Lisozim:

• secara alami merupakan agen antibakteri. Banyak digunakan dalam

industry pangan karena dapat merusak struktur karbohidrat dari dinding
sel bakteri.
• Lisozim juga banyak digunakan dalam menangani pasien HIV karena
memiliki Rnase A dan Rnase U yang dapat mendegradasi RNA virus.

Ezim litik-bakteriofage:

• untuk merusak dinding sel bakteri pathogen seperti Streptococcus

pneumonia, Bacillus anthracis dan Clostridium perfringens.

Kitinase:

• untuk mendegradasi dinding sel dari organisme pathogen seperti fungi, 26

protozoa dan Helminthes.

 ENZYMES FOR THE TREATMENT OF CANCER

 Enzim PEGylated arginine deaminase: merupakan enzim pendegradasi

arginine. Enzim ini dapat menghambat pertumbuhan melanoma dan
carcinoma.
 Recently, another PEGylated enzyme, Oncaspar1 (pegaspargase),
already in use in the clinic, has shown better results for the treatment
of children with newly diagnosed standard-risk acute lymphoblastic
leukemia than the native, bacterial asparaginase.
 Whereas normal cells are able to synthesize asparagine, cancer cells are
not and die in the presence of this asparagine-degrading enzyme.
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Michel Vellard. (2003).The enzyme as drug: application of enzymes as
pharmaceuticals. Current Opinion in Biotechnology. Vol.14: 444–450
 29
Michel Vellard. (2003).The enzyme as drug: application of enzymes as
pharmaceuticals. Current Opinion in Biotechnology. Vol.14: 444–450
 30
Michel Vellard. (2003).The enzyme as drug: application of enzymes as
pharmaceuticals. Current Opinion in Biotechnology. Vol.14: 444–450
PROTEIN AS DRUG SUBSTANCES

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 proteins essentially provide the amino acids required for the growth
and subsequent repair of impaired animal tissue.
 Composition of Proteins: Proteins, are composed of a host of vital
elements, such as: C, H, O, N, P, S, and Fe, which ultimately make up the
greater segment of the animal and plant tissue.
 Sources: Interestingly, the various known and important sources of
proteins are, namely: cheese, milk, eggs, meat, fish, and certain
vegetables viz., soybeans are recognized as the best sources.

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TUGAS
1. Apa peran protein?
2. Protein tersusun atas asam amino. Sebutkan nama-nama
asam amino
3. Asam amino ada dua kelompok--- asam amino esensial dan
nonesensial. Apa perbedaannya? Berdasarkan jawaban
nomor 3, kelompokkan asam-asam amino tersebut yang
termasuk ke dalam esensial dan nonesensial.
4. Ada berapa modifikasi protein? Sebutkan dan berikan
contoh peran masing-masing!

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PROTEINS USED AS DRUGS

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1. COMPLEMENT PROTEIN (COMPLEMENT FACTOR C-3)
[LATIN; COMPLERE = TO COMPLETE]

 Protein komplemen merupakan protein yang ada di dalam darah yang

berperan dalam mekanisme pertahanan tubuh.
 Protein komplemen diberi lambing C1 hingga C9. komplemen C3 dan
C5 diketahui sebagai komplemen paling penting.
 Kekurangan factor C3 dapat meningkatkan infeksi mikroba.
 Kekurangan factor C5 sd C9 berkaitan dengan penyakit autoimun,
seperti:
• glomerulonephritis
• systemic lupus erythematosus

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2. GELATIN [LATIN: GELATINA = GELATIN]

 Gelatin merupakan protein yang diperoleh dari hidrolisis kolagen.

Terdapat kulit, tulang dan persendian pada Animalia.
 Umum digunakan dalam bidang makanan: jeli
 Dalam bidang farmasi: soft-gelatine capsules untuk Vitamin E, garlic
pearls etc.; hard-gelatine capsules untuk chloramphenicol,
tetracycline, acetamenophen (paracetamol) Tylenol (R) in US
 Mikrobiologi: medium kultur mikroorganisme

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 Tipe-tipe Gelatin:
(a) Absorbable Gelatin Sponge: It is a sterile, white, tough, and finely porous
spongy, water insoluble, and absorbable substance. Even though it is water-
insoluble but it is adequately absorbed in body fluids.
The various uses of absorbable gelatin sponge are as follows:
• an effective haemostatic,
• as a localized anticoagulant, and
• when placed upon a surgical incision after being duly moistened with sterile
NaCl solution, it gets slowly absorbed within a span of 4-6 weeks.
(b) Absorbable Gelatin Film: Absorbable gelatin film refers to a light amber
coloured, sterile, non-antigenic thin film invariably produced from a especially
prepared gelatin-formaldehyde solution by careful drying followed by
subsequent sterilization.
 Absorbable gelatin film is largely employed in the form of saline-soaked
rubber-like thin sheets chiefly in surgical repair of such observed defects in
membranes, such as: dura and pleura matter, where it grossly serves as a
mechanical means of protection, replacement matrix, and temporary 40

supportive structural wall.

3. COLLAGEN [SYNONYM: OSSIEN]: (GREEK:
KOLLA = GLUE, + GENNAN = TO PRODUCE)
 Kolagen merupakan protein kuat dan
berserat yang ditemukan pada jaringan
penghubung, termasuk kulit, tendon,
ligament, tulang, dan kartilago.
 Kolagen merupakan jaringan dental
(kecuali enamel gigi): membentuk matriks
dentin, sementum, dan tulang alveolar.
Kolagen mengikat gigi pada rahang atas
dan bawah.
 Kolagen banyak digunakan dalam emulsi
fotografi, sutura, dan pembungkus
makanan (berjel).
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 4. CASEIN [LATIN: CASEUS = CHEESE]

 Casein designates the principal protein in milk. It essentially provides

all the amino acids that are necessary for the growth and development
in humans.
 Peran kasein:
 Kasein direkomendasikan sebagai suplemen makanan bagi pasien
pra-operasi dan post-operasi.
 Kasein sebagai bahan dasar dalam pembuatan enzim proteolitik.
 Kasein sebagai agen pengemulsi.
 Kasein untuk merekatkan kertas dan tekstil.
 Kasein dapat digunakan sebagai agen adhesive pada cat dan plastic
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kasein.
Casein Variants:
(a) Lactalbumin: Lactalbumin refers to the albumin of milk and cheese; and
it is a soluble simple protein. It is present in relatively higher
concentration in human milk in comparison to the cow’s milk.
(b) Lactoglobulin: Lactoglobulin refers to a protein found most abundantly
in milk. Both casein and lactoglobulin are the most common proteins
invariably seen in the cow’s milk.
(c) Acid Casein: The warm skimmed milk when acidified with a diluted
mineral acid, the whey usually gets separated. The solid curd is duly
separated by any suitable means, residual solid mass is now washed
thoroughly, dried and pulverized to obtain acid casein powder.
(d) Rennet Casein: The skimmed milk is adequately treated with an enzyme,
rennet extract, whereby the product is first separated carefully, and
subsequently purified to obtain the Rennet Casein.
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 5. LECTINS [SYNONYMS: AGGLUTININS;
AFFINITINS; PHASINS; PROTECTIN
 Lektin berperan dalam menstimulasi limfosit untuk mengalami
pembelahan.
 Lektin dapat diperoleh dari berbagai sumber: kulit batang, fungi, telur
segar, akar, mikroorganisme, cairan tubuh hewan vertebrata tingkat
rendah, avertebrata, rumput laut dan spons, dan membran sel mamalia.
 Natural Sources of Lectins:
o abrin: Abrus precaturius;
o concanavalin A: Conovalia ensioformis;
o green marine algae: Codium fragile;
o red kidney bean: Phaseolus vulgaris;
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o horse gram: Dolichos biflorus.
• Lectins are not used directly as a medicine, but they do have the
following usages elsewhere, namely:
 For determining blood-groups; and for carrying out erythrocytic
polyagglutination investigative studies.
 For performing histochemical studies related to either normal and
pathological status.
 For establishing structural elucidation studies of the carbohydrate
bearing molecules.
 For carrying out the mitogenic stimulation of lymphocytes.
 As tools for studying cell-surface properties in cancer research.

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 6. THAUMATIN [SYNONYM: TALIN;]

 Thaumatin merupakan protein yang memiliki rasa

manis, diekstraksi dari buah-buahan tropis. Contoh:
Thaumatococcus danielli Benth., Marantaceae, found
extensily in West Africa from Sierre Leone to Zaire, in
Sudan and Uganda.
 Thaumatin terdiri dari 5 bentuk: thaumatins I, II, III, b,
dan c. ke-5 thaumatin tersebut 100.000 kali lebih manis
dari sukrosa, sehingga berpotensi sebagai pemanis
rendah kalori.
 Banyak digunakan dalam industri permen karet dan
penyegar nafas.
 Talin merupakan salah satu produk ternama yang 47

dipasarkan di Jepang, US, dan Eropa.

H.A. Daniel Lagassé, Aikaterini Alexaki, Vijaya L. Simhadri, Nobuko H. Katagiri, Wojciech Jankowski, Zuben E. 48
Sauna, Chava Kimchi-Sarfaty. Recent advances in (therapeutic protein) drug development. F1000Research
2017, 6(F1000 Faculty Rev):113 Last updated: 07 FEB 2017.
H.A. Daniel Lagassé, Aikaterini Alexaki, Vijaya L. Simhadri, Nobuko H. Katagiri, Wojciech Jankowski, Zuben E. 49
Sauna, Chava Kimchi-Sarfaty. Recent advances in (therapeutic protein) drug development. F1000Research
2017, 6(F1000 Faculty Rev):113 Last updated: 07 FEB 2017.
H.A. Daniel Lagassé, Aikaterini Alexaki, Vijaya L. Simhadri, Nobuko H. Katagiri, Wojciech Jankowski, Zuben E. 50
Sauna, Chava Kimchi-Sarfaty. Recent advances in (therapeutic protein) drug development. F1000Research
2017, 6(F1000 Faculty Rev):113 Last updated: 07 FEB 2017.
H.A. Daniel Lagassé, Aikaterini Alexaki, Vijaya L. Simhadri, Nobuko H. Katagiri, Wojciech Jankowski, Zuben E. 51
Sauna, Chava Kimchi-Sarfaty. Recent advances in (therapeutic protein) drug development. F1000Research
2017, 6(F1000 Faculty Rev):113 Last updated: 07 FEB 2017.
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