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. Harper’s 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 → Inhibits peptidyltransferase
 Pactamycin → Inhibits positioning of t-RNA1Met on the 40S
ribosome
 Showdomycin → Inhibits formation of the EF -tRNA Met GTP complex
*also active on prokaryotic ribosomes 2 1
 Sparsomycin → Inhibits translocation
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 Inhibits translocation

 Rifamycin Inhibits RNA synthesis binding to

RNA polymerase
 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 chains—two
alpha globin and two beta globin. The two major types of, alpha and beta, are
named after defects in these protein chains

α – 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.

β – 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