PROTEIN BIOSYNTHESIS

PROGRAM KBK
FK-UKI

Prof. Dr. drh. Maria Bintang, MS

GURU BESAR BIOKIMIA

REFERENCES
Lehninger. 2000. Principles of biochemistry 3rd Ed.
Michael W. King. 2006. Medical Biochemistry.
Murray R K, Granner D k, Mayers P a & Rodwell V w.

2003. Harpers Illustrated Biochemistry. 26th Ed.

Pratt,C.W.and Cornely K. 2004. Essential
Biochemistry. Wiley International Edition.
Stryer, Lubert 1995. Biochemistry.4th Ed.

Aminoacyl tRNA
Sintetase + ATP

Translation : ELONGASI
Peptidyl transferase
+ EF1 + GTP

Translation : ELONGASI

EF2

RF + GTP

INTERCALATNG AGENT

BASE ANALOGS

ALKYLATING AGENT

HYDROXILATING AGENT

DEAMINATING AGENT

Inhibitor of Protein Synthesis in Eukaryotes

Abrin, Ricin
Inhibits binding of aminoacyl t-RNA
Diphtheria toxin Catalyzes a reaction between NAD and EF2 to
yield an inactive factor. Inhibits translocation
Chloramphenicol* Inhibits peptidyltransferase of mitochondrial
ribosomes. Is inactive against cytoplasmic ribosomes
Puromycin*
Causes premature chain termination by acting
as an analogue of charged t-RNA
Fusidic acid*
Inhibits translocation by altering an elongation factor
Cycloheximide

Pactamycin

ribosome
Showdomycin
Sparsomycin

Inhibits peptidyltransferase
Inhibits positioning of t-RNA1Met on the 40S
Inhibits formation of the EF2-tRNA1Met GTP complex
Inhibits translocation

*also active on prokaryotic ribosomes

Antibiotics Inhibitor of Protein Synthesis in

Prokaryotes

Tetracycline
Inhibits positioning of
t-TNA on A side in ribosome

Streptomycin
Inhibits formation of the EF2 tRNA1Met on the 30 S ribosome

Chloramphenicol Inhibits peptidyltransferase

on ribosome

Erythromycin

Rifamycin Inhibits RNA synthesis

to RNA polymerase

Inhibits translocation
binding

Biosinthesis Protein disorders

Lactose Intolerance
Lactose intolerance is a clinical syndrome of 1 or more of the following:
abdominal pain, diarrhea, nausea, flatulence, and/or bloating after the
ingestion of lactose or lactose-containing food substances
Primary : Lactase Deficiency (genetic)
Secondary : lactose malabsorption

Thalassemia

Thalassemia is a heterogenous group of haemopoetic disorder which results

from genetic defect in either one or both polypeptide chains of the
haemoglobin molecules. Reduced synthesis of one of the globin chains
causes the formation of abnormal hemoglobin molecules, and this in turn
causes the anemia which is the characteristic presenting symptom of the
thalassemias.

Normal hemoglobin, also called hemoglobin A, has four protein chainstwo

alpha globin and two beta globin. The two major types of, alpha and beta, are
named after defects in these protein chains
thalassemia :

Four genes are needed to make enough alpha globin protein chains. Alpha
thalassemia trait occurs when one or two of the four genes are missing. If more
than two genes are missing, the result is moderate to severe anemia.
The most severe form of alpha thalassemia is known as alpha thalassemia major or
hydrops fetalis. Babies with this disorder usually die before or shortly after birth.

thalassemia :

Two genes (one from each parent) are needed to make enough beta globin protein
chains. Beta thalassemia occurs when one or both genes are altered.
The severity of beta thalassemia depends on how badly one or both genes are
affected. If both genes are affected, the result is moderate to severe anemia. The
severe form of beta thalassemia also is known as thalassemia major or Cooley's
anemia.

 Symptom of thalassemia :

Fatique
Weakness
Pale appearance
Joundice
Protruding abdomen
Spleen enlargement
Liver enlargement
Shortness of breath
Heart enlargement
Dark urine

Hypoalbuminemia
Hypoalbuminemia is a deficit of albumin in the blood,
which produced by liver
The causes of hypoalbuminemia are :
Renal (kidney) dysfunction
Liver disease
Inflammatory bowel disease
Infections, such as tuberculosis
Symptom
Blood albumin levels are significantly lowered
Muscle weakness, fatigue, or cramps, poor appetite,
swelling in one part of your body (such as your legs),
abdomen is swollen with fluid (called, ascites)
Albumin levels below 3.5 g/dl

Liver fibrosis

The Fibrosis Process

The injury or death (necrosis) of hepatocytes stimulates inflammatory
immune cells to release cytokines, growth factors, and other chemicals.
These chemical messengers direct support cells in the liver called hepatic
stellate cells to activate and produce collagen, glycoproteins (such as
fibronectin), proteoglycans, and other substances. These substances are
deposited in the liver, causing the buildup of extracellular matrix
(nonfunctional connective tissue). At the same time, the process of breaking
down or degrading collagen is impaired. In a healthy liver, the synthesis
(fibrogenesis) and breakdown (fibrolysis) of matrix tissue are in balance.
Fibrosis occurs when excessive scar tissue builds up faster than it can be
broken down.

Symptom of liver fibrosis

Nausea, poor appetite, accumulation of fluid in the abdomen
(ascites)
SGOT and SGPT increase
USG Liver enlargement

Liver cirrhosis

Cirrhosis of the liver refers to scarring of the liver which results in

abnormal liver function as a consequence of chronic (long-term) liver
injury.
Ongoing injury leads to the development of scar tissue in the liver, a
process called fibrosis, because of collagen synthesis disorder.
Disorders of albumin synthesis (liver cirrhosis, malabsorption, nephrosis
and protein-losing enteropathy)
SGOT and SGPT increase USG : LIVER SHRINK
Symptom of liver cirrhosis :
Symptoms at first : The two major problems that eventually cause symptoms
are loss of functioning liver cells and distortion of the liver caused by scarring.
The person may experience fatigue, weakness, and exhaustion. Loss of
appetite is usual, often with nausea and weight loss.
Later stages : jaundice may occur caused by the buildup of bile pigment that
is passed by the liver into the intestine. Some people with cirrhosis experience
itching due to bile products that are deposited in the skin. Gallstones often
form because not enough bile reaches the gallbladder. may develop fluid
retention in the abdomen which may be complicated by infections.

Muscle atrophy
Muscle atrophy occurs by a change in the normal balance
between protein synthesis and protein degradation.
The simple loss of muscle mass (atrophy ), or the age-related
decrease in muscle function (sarcopenia).
There are other diseases which may be caused by structural
defects in the muscle (muscular dystrophy ),
Or by inflammatory reactions in the body directed against
muscle (the myopathies).
Myoglobin can serve as a biomarker of heart attack, since blood
myoglobin levels rise in two to three hours following muscle
injury.
Myoglobin is released from damaged muscle tissue