Insulin

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Insulin

• Polypeptide hormone produced by pancreatic beta
  cells that regulates carbohydrate homeostasis.
  Converted by proteolysis from the single chain
  proinsulin, q.v., to the active dimer composed of
  51 amino acid residues mol wt 6000. Regulates
  carbohydrate and lipid metabolism, and influences
  protein synthesis. Insulin was the first protein
  for which the chemical structure and mol wt were
  determined.

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Insulins
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Carbon - Red Oxygen - Green
Nitrogen - Blue Sulfur - Pink
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Insulin

• Mechanism of Action
• The primary activity of insulin, is regulation
  of glucose metabolism. Insulin and its analogs
  lower blood glucose levels by stimulating
  peripheral glucose uptake, especially by skeletal
  muscle and fat, and by inhibiting hepatic glucose
  production. Insulin inhibits lipolysis in the
  adipocyte, inhibits proteolysis, and enhances
  protein synthesis.

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Insulins

• ?-??????
  ?-??????
• 8 9 10
  30
• ??????? THR SER ILE THR
• ??????? ALA SER VAL ALA
• ??????? THR SER ILE ALA

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Insulin glulisine injection

• Insulin glulisine is produced by recombinant DNA
  technology utilizing a non-pathogenic laboratory
  strain of Escherichia coli (K12).

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Insulin glargine is a human insulin analog that
has been designed to have low aqueous solubility
at neutral pH.

• Insulin glargine differs from human insulin in
  that the amino acid asparagine at position A21 is
  replaced by glycine and two arginines are added
  to the C-terminus of the B-chain. Chemically, it
  is 21 A -Gly-30 B a-L-Arg-30 B b-L-Arg-human
  insulin and has the empirical formula C 267 H 404
  N 72 O 78 S 6 and a molecular weight of 6063.

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Insulin aspart

• NovoLog is homologous with regular human insulin
  with the exception of a single substitution of
  the amino acid proline by aspartic acid in
  position B28, and is produced by recombinant DNA
  technology utilizing Saccharomyces cerevisiae
  (baker's yeast) as the production organism.
  Insulin aspart has the empirical formula
  C256H381N65079S6 and a molecular weight of 5825.8.

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APIDRA (insulin glulisine rDNA origin) is a
human insulin analog that is a rapid-acting,
parenteral blood glucose lowering agent. Insulin
glulisine is produced by recombinant DNA
technology utilizing a non-pathogenic laboratory
strain of Escherichia coli (K12). Insulin
glulisine differs from human insulin in that the
amino acid asparagine at position B3 is replaced
by lysine and the lysine in position B29 is
replaced by glutamic acid. Chemically, it is
3B-lysine-29B-glutamic acid-human insulin, has
the empirical formula C258H384N64O78S6 and a
molecular weight of 5823. It has the following
structural formula                             
                                                  
                                          
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LEVEMIR (insulin detemir rDNA origin
injection) is a sterile solution of insulin
detemir for use as an injection. Insulin detemir
is a long-acting basal insulin analog, with up to
24 hours duration of action, produced by a
process that includes expression of recombinant
DNA in Saccharomyces cerevisiae followed by
chemical modification. Insulin detemir differs
from human insulin in that the amino acid
threonine in position B30 has been omitted, and a
C14 fatty acid chain has been attached to the
amino acid B29. Insulin detemir has a molecular
formula of C267H402O76N64S6 and a molecular
weight of 5916.9. It has the following structure
                                               
                                                  
                                                  
                        
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Humalog (insulin lispro, rDNA origin) is a human
insulin analog that is a rapid-acting,
parenteral blood glucose-lowering agent.
Chemically, it is Lys(B28), Pro(B29) human
insulin analog, created when the amino acids at
positions 28 and 29 on the insulin B-chain are
reversed. Humalog is synthesized in a special
non-pathogenic laboratory strain of Escherichia
coli bacteria that has been genetically altered
by the addition of the gene for insulin
lispro. Humalog has the following primary
structure                                     
                                                  
                            
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Cerezyme (imiglucerase for injection) is an
analogue of the human enzyme, (beta)-glucocerebro
sidase produced by recombinant DNA technology.
(beta)-Glucocerebrosidase ((beta)-D-glucosyl-N-acy
lsphingosine glucohydrolase, E.C. 3.2.1.45) is a
lysosomal glycoprotein enzyme which catalyzes
the hydrolysis of the glycolipid
glucocerebroside to glucose and ceramide.
Cerezyme is produced by recombinant DNA
technology using mammalian cell culture (Chinese
hamster ovary). Purified imiglucerase is a
monomeric glycoprotein of 497 amino acids,
containing 4 N-linked glycosylation sites (Mr
60,430). Imiglucerase differs from placental
glucocerebrosidase by one amino acid at position
495 where histidine is substituted for arginine.
The oligosaccharide chains at the glycosylation
sites have been modified to terminate in mannose
sugars. The modified carbohydrate structures on
imiglucerase are somewhat different from those on
placental glucocerebrosidase. These
mannose-terminated oligosaccharide chains of
imiglucerase are specifically recognized by
endocytic carbohydrate receptors on macrophages,
the cells that accumulate lipid in Gaucher
disease.
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• ?????????????
• Cyclosporin A immunosuppressant
• Fermentation of Tolypocladium inflatum

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Interferons immunostimulants

• Products from cells which contain
• recombinant DNA
• Hepatitis B vaccine (recimbinant DNA)
• ?????????? ??????? Captopril, Enalapril,
• Lisinopril, Ramipril - antihypertonics

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Ramipril
2 S ,3a S ,6a S -1-(2 S )-2-(1 S )-(Ethoxy
carbonyl)- 3-phenylpropylamino-1-oxopropyl octa
hydrocyclopenta b pyrrole-2-carboxylic acid
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Ramipril is a 2-aza-bicyclo 3.3.0-octane-3-carboxylic acid derivative. It is a white, crystalline substance soluble in polar organic solvents and buffered aqueous solutions. Ramipril melts between 105C and 112C. Its empiric formula is C23H32N2O5, and its molecular weight is 416.5. Ramiprilat, the diacid metabolite of ramipril, is a non-sulfhydryl angiotensin converting enzyme inhibitor. Ramipril is converted to ramiprilat by hepatic cleavage of the ester group. Altace (ramipril) is supplied as hard shell capsules for oral administration containing 1.25 mg, 2.5 mg, 5 mg, and 10 mg of ramipril. The inactive ingredients present are pregelatinized starch NF, gelatin, and titanium dioxide. The 1.25 mg capsule shell contains yellow iron oxide, the 2.5 mg capsule shell contains DC yellow 10 and FDC red 40, the 5 mg capsule shell contains FDC blue 1 and FDC red 40, and the 10 mg capsule shell contains FDC blue 1.

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Enalapril

• maleate

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Vasotec is the maleate salt of enalapril, the
ethyl ester of a long-acting angiotensin
converting enzyme inhibitor, enalaprilat.
Enalapril maleate is chemically described as
(S)-1-N-1-(ethoxycarbonyl) -3-phenylpropyl-L-a
lanyl -L-proline, (Z)-2-butenedioate salt
(11). Its empirical formula is
C20H28N2O5C4H4O4. Enalapril maleate is a white
to off-white, crystalline powder with a
molecular weight of 492.53. It is sparingly
soluble in water, soluble in ethanol, and freely
soluble in methanol. Enalapril is a pro-drug
following oral administration, it is
bioactivated by hydrolysis of the ethyl ester to
enalaprilat, which is the active angiotensin
converting enzyme inhibitor. Enalapril maleate is
supplied as 2.5 mg, 5 mg, 10 mg, and 20 mg
tablets for oral administration. In addition to
the active ingredient enalapril maleate, each
tablet contains the following inactive
ingredients lactose, magnesium stearate, starch,
and other ingredients. The 2.5 mg, 10 mg and 20
mg tablets also contain iron oxides.
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VASOTEC I.V.(Enalaprilat) is a sterile aqueous
solution for intravenous administration.
Enalaprilat is an angiotensin converting enzyme
inhibitor. It is chemically described as
(S)-1-N-(1-carboxy-3-phenylpropyl)- L-alanyl-L-p
roline dihydrate. Its empirical formula is
C18H24N2O52H2O. Enalaprilat is a white to
off-white, crystalline powder with a molecular
weight of 384.43. It is sparingly soluble in
methanol and slightly soluble in water. Each
milliliter of VASOTEC I.V.contains 1.25 mg
enalaprilat (anhydrous equivalent) sodium
chloride to adjust tonicity sodium hydroxide to
adjust pH water for injection, q.s. with
benzyl alcohol, 9 mg, added as a preservative
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