Structure and Role of Enzymes in Steriodogenenic pathways

1. Presented by :
SUNIL KUMAR SAHOO

2. Introduction
Synthesis of cholesterol
Synthesis of steroids
Involved Enzymes
Conclusion
References

3.  Biosynthesis of Steroids occur in the
steroidogenic tissue of all the specific gland
of organism inside the mitochondria.
 Acetyl CoA is the precursor molecule for the
synthesis of cholesterol .
 Cholesterol synthesized in two different
pathways--
Mevalonatepathway/
Isoprenoid pathway /
Hma CoA reductase pathway
Non mevalonate pathway
Occurance Eukaryotes ,Archea and some
bacteria
plants and protozoa & few
Bacteria .
Organels involved mitochondria plastid
Example Human Malarial parasite,
Mycobacterium tuberculosis
etc .

4. SYNTHESIS OF CHOLESTEROL
Acetate/Acetyl CoA
Mavalonate
Activated isoprene
(Dimethyl pyrophosphate +
delta-isopentenyl pyrophosphate)
Squalene
Cholesterol
•-----Acetyl-CoA acetyl transferase  Acetoacetyl-CoA_
•HMG-CoA synthase - -> β-Hydroxy-β-methylglutaryl-CoA
• HMG-CoA reductase -------
•---Mevalonate 5-phosphotransferase – ->5-Phosphomevalonate
•Phosphomevalonate kinase - 5-pyrophosphomevalonate
•Phosphomevalonate decarboxylase-3-phospho-5pyrophosphomevalonate
•Pyrophosphomevalonate decarboxylase  delta-isopentenyl pyrophosphate
•Isopentinylpyrophosphate isomerase  Dimethyl pyrophosphate-----------
•--Pentinyl transferase -Geranyl pyrophosphate
•Pentinyl pyrophosphate - Farnesyl pyrophosphate
•Squalene synthase --- Squalene ------
•---squalene monooxiginase  Squelene 2,3-epoxite
•Plants--- Stigma sterol
•Fungi-- Ergasterol
•Animal-Cyclase --- Lanosterol -------

5. SYNTHESIS OF STEROIDS

6. HMG-CoA reductase
 1.1.1.34
 Acting on the CH-OH group of donors
 With NAD+ or NADP+ as acceptor
 hydroxymethylglutaryl -CoA reductase
(NADPH)
 Chains: A, B, C, D
 Length: 467 amino acids
 Theoretical weight: 50.02 Kda
 Source organism: Homo sapiens
(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH
+ 2 H+
ENZYMES OF STEROID BIOSYNTHESIS

7. Cont..
Source-https://www.ebi.ac.uk/pdbe/entry/pdb/1dqa/protein/1

8. HMG-CoA synthase
Source-https://www.ebi.ac.uk/pdbe/entry/pdb/2p8u/analysis
Source-https://biocyc.org/META/NEW-IMAGE?type=REACTION&object=HYDROXYMETHYLGLUTARYL-COA-SYNTHASE-RXN#
2.3.3.10
Group transfer
Acyltransferases-
Hydroxymethylglutaryl-CoA synthase
Chains: A, B
Length: 478 amino acids
Theoretical weight: 53.33 Kda
Source organism: Homo sapiens

9. Cont..

10. alcohol sulfotransferase
 2.8.2.2.
 Transferases
 Transferring sulfur-containing groups
 alcohol sulfotransferase
 Chain: A
 Length: 506 amino acids
 Theoretical weight: 55.12 Kda
 Source organism: Streptomyces sp. SA-COO
 Expression system: Escherichia coli

11. Cont..
Source of image :http://www.ebi.ac.uk/pdbe/entry/pdb/3b3r/analysis

12. steryl-sulfatase
 3.1.6.2
 Hydrolases
 Acting on ester bonds
 Sulfuric Ester Hydrolases
 Chain: A
 Length: 562 amino acids
 Theoretical weight: 63.05 Kda
 Source organism: Homo sapiens

13. Cont..
Image source :https://www.ebi.ac.uk/pdbe/entry/pdb/1p49/analysis

14. Diphosphomevalonate decarboxylase-
 4.1.1.99
 Carbon-carbon lyases
 Carboxy-Lyases
 phosphomevalonate decarboxylase
 Chains: A, B
 Length: 414 amino acids
 Theoretical weight: 45.81 Kda
 Source organism: Mus musculus

15. Cont..
Source of image:https://www.ebi.ac.uk/pdbe/entry/pdb/3f0n/analysis

16. steroid Δ-isomerase
 5.3.3.1.
 Intramolecular isomerases
 Transposing C=C Bonds
 steroid Δ-isomerase
 Chains: A, B, C, D
Length: 135 amino acids
Theoretical weight: 15.05 KDa
Source organism: Pseudomonas putida
Expression system: Escherichia coli

17. Cont…

18. Name of steroids Example Functions
Glucocorticoids Cortisol anti-inflammatory.
influence all forms of metabolism (water-electrolyte, lipid, protein and
carbohydrate)
anti-allergic effect.
effects on the cardiovascular system.
stimulation of the formation of blood platelets, fragments of megakaryocytes
and red blood cells.
suppress the production of sex hormones
Mineralocorticoids Aldosterone Maintain blood volume and Blood pressure by increasing sodium reabsorption in
kidney.
Androgen Testosterone Development of secondary sexual characteristics
Estrogen Estriol protects the breast tissue.
helps to maintain bone density and
dryness of the vaginal mucosa and urethra.
 increases the amount of ‘good’cholesterol
& reduces the amount of ‘bad’ cholesterol.
enhances thinking, concentration, and
mood.
protects the cardiovascular system and
reduces the viscosity of the blood.
Progesterone Prepare uterus lining for implantation of ovum
Diseases
May be pre natal or post natal .
Pre natal include mutation that result in absence of specific enzymes .This result in
disease like –
Parkinson , Distonia ,MERRF, MND,Corea,Atassia, MELAS .

19. • Text book of medical physiology _Gyton and Hall
• Principle of Biochemistry_David L.Nelson, Michael M.cox
• http://www.sbcs.qmul.ac.uk
• https://www.ebi.ac.uk
• https://enzyme.expasy.org