The document discusses the biosynthesis of steroids from cholesterol. It begins by explaining that steroids are synthesized from acetyl-CoA through the mevalonate pathway in the mitochondria. It then provides details on the multi-step process by which cholesterol is synthesized from acetyl-CoA, including the involved enzymes such as HMG-CoA reductase. The document further discusses how cholesterol is converted to different steroids through cyclization and oxidation reactions. It also lists some example steroids and their functions, as well as diseases related to deficiencies in steroid biosynthesis enzymes.

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