Adichunchanagiri

Institute of Medical

Sciences

Chief Patron

Paramapoojya

Sri Sri Sri

Nirmalanandanatha

Mahaswamiji

Chief Advisor

Dr Shivaramu M.G.

Principal A.I.M.S.

Chief Editor

Dr Aliya Nusrath.

Professor & Head

Dept. of Biochemistry

Editorial Board

Dr. Rajeshwari A.

Assoc. Professor

Sri. Somashekar G.N.

Asst. Professor

Dr. Chikkanna D.

Asst. Professor

Dr Maithri C.M.

Asst. Professor

Dr Asha Rani N.

Asst. Professor

Members

Dr. Prathibha K.

Tutor cum PG

Dr Namitha D.

Tutor cum PG

Contact information:

biomedaims@gmail.com

Biomed

Dept of Biochemistry ___________________________________________________

News letter VOLUME 1 ISSUE 3 JULY 2013

___________________________________________________

From Editor’s Desk Greetings

With immense pleasure we are releasing the third

issue of Biomed. Medical field is ever growing with newer

trends. In this context we have tried to throw light on newer protein frontiers in health and disease in this edition.

Many a changes have taken place in the department.

It was disheartening to let go of our senior technician Sri

Mahalinge Gowda after 25 years of his service. However as

it is said life goes on, we also had many a cause for

celebration. Our department was expanded with newly

furnished research laboratory and other facilities. Also we

congratulate and welcome the MCI grant for 150

admissions of undergraduates as well as the Government

approval of University status to our institution.

Send off party of Sri Mahalinge Gowda

First Row (From left to right): Dr Asha Rani, Dr Maithri, Dr Rajeshwari A, Sri Mahalinge Gowda,

Dr Aliya Nusrath, Sri Somashekhar and Dr Chikkanna

Second Row (From left to right): Sri Hongere Gowda, Sri

Yateesh, Sri Mahalinge Gowda, Sri Ramesh, Sri Shankare Gowda and Sri Krishne Gowda

Saposin B deficiency

Arylsulfatase A deficiency results in Metachromatic leukodystrophy (MLD). There are three clinical

subtypes, which are primarily distinguished by age of onset, late-infantile MLD (50-60%), juvenile

MLD(20-30%) and adult MLD (15-20%). MLD is suspected in individuals with progressive neurological

functions and MRI evidence of leucodystrophy. MLD may be due to ARSA enzyme activity in leucocytes

less than 10% of normal controls. However assay of ARSA enzyme activity cannot distinguish between

MLD and ARSA pseudodeficiency, where ARSA enzyme activity is 5% to 20% of normal controls and does

not cause MLD. Thus the diagnosis of MLD must be confirmed by one or more tests like molecular testing

of the ARSA, the only gene in which mutation causes ARSA deficiency, urinary excretion of sulfatides and

presence of metachromatic lipid deposit in nervous tissue.

High prevalence of ARSA pseudodeficiency with low levels of ARSA enzyme activity is found in

association with many disorders and it is diagnosed with the neurodegenerative disorder is often consider

due to deficiency of ARSA activity. However schizophrenia depression, substance abuse, multiple sclerosis

and various forms of dementia frequently seen in general population may not be due to the low levels of

ARSA activity.

Saposin B is an activator protein, is required for the degradation of sulfatide by Arylsulfatase A

(ARSA) and hydrolysis of globotriaosylceramide and digalactosylceramide by α-galactosidases. Saposins

(A, B, C and D) are small glycoprotiens derived from the precursor protein prosaposin by proteolytic

cleavage. Prosaposin is 65-70KDa protein exists both as secretory protein as well as integral membrane

protein and as neurotropic activities. Deficiency of saposin due to gene defect results in the accumulation of

multiple sphingolipids leading to the complex sphingolipidosis with early fatal consequences. Saposin B

deficiency causes MLD like disorder due to the disrupted glycolipid degradation, MLD like clinical

presentation leukodystrophy on MRI, normal ARSA enzyme activity and excess urinary sulfatide excretion

or sulfatide storage. Diagnosis can be evaluated on depressed sulfatide degradation by culture cells,

immunochemical assessment of saposin B levels or sequence analysis of gene encoding saposin B.

Dr. Rajeshwari A Assoc. Professor, Biochemistry

Irisin The benefit of exercise has been extensively studied and is the method for non-pharmacological

treatment of cardiovascular and metabolic diseases like diabetes mellitus, obesity etc. Exercise is known to

induce weight loss and improve glucose homeostasis. However, the molecular mechanism behind it

remained largely unexplained. In 2012, a hormone called Irisin named after Greek goddess iris, was

discovered by Bruce M Spigelmen et al which was found to be responsible for exercise induced weight loss

and improved glucose homeostasis. It is a PGC - 1α induced myokine, a 112 AA polypeptide secreted from

muscle into the bloodstream in response to exercise.

There are two types of adipose tissues in our body namely, white adipose tissue and brown adipose

tissue. The main function of white adipose tissue is to store fat whereas brown adipose tissue has non

shivering thermogenic properties due to expression of uncoupling protein – 1 and increased mitochondrial

content.

As per the molecular mechanism, exercise is the stimulus for release of PGC1α which is a co-

activator of PPAPγ (peroxisome proliferator activated receptor). This in turn stimulates the expression of

FNDC5 which in turn is proteolytically cleaved to release the active hormone Irisin. This Irisin has cell

surface receptors. It increases the expression of UCP1 and cidea mRNA, which causes the browning of

primarily subcutaneous and also of visceral adipose tissue and thereby inducing thermogenesis. So Irisin

causes white adipose tissue to get converted to brown adipose tissue and thereby reduction of insulin

resistance and improvement of glucose homeostasis. Hence it may be useful as anti-obesity treatment and

anti-diabetic treatment. Hence Irisin may be useful in the treatment of obesity, diabetes and metabolic

syndrome especially to people who cannot exercise because of physical limitations.

At present, all the effects of Irisin are seen in mice, because of its 100% sequence homology, it is

being assumed to have same effect in humans for whom clinical trials are being conducted.

Dr. Maithri C.M, Assistant Professor, Biochemistry

Sirtuin or Sir2 proteins

Sirtuin or Sir2 proteins are a class of proteins that possess either mono-ribosyltransferase, or deacylase

activity. The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2',the gene

responsible for cellular regulation in yeast. Sirtuins have been implicated in influencing a wide range of

cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy

efficiency and alertness during low-calorie situations. Sirtuins can also control circadian clocks and

mitochondrial biogenesis. Mammals possess seven sirtuins (SIRT1-7) that occupy different subcellular

compartments such as the nucleus (SIRT1, -2, -6, -7), cytoplasm (SIRT1 and SIRT2) and the mitochondria

(SIRT3, -4 and -5).

Clinical significance

Sirtuin activity is inhibited by nicotinamide, which binds to a specific receptor site, so it is thought that

drugs that interfere with this binding should increase sirtuin activity. Development of new agents that would

specifically block the nicotinamide-binding site could provide an avenue for development of newer agents to

treat degenerative diseases such as cancer, Alzheimer's, diabetes, atherosclerosis, and gout.

Alzheimer's disease: SIRT1 deacetylates and coactivates the retinoic acid receptor beta that upregulates the

expression of alpha-secretase (ADAM10). Alpha-secretase in turn suppresses beta-amyloid production.

Furthermore, ADAM10 activation by SIRT1 also induces the Notch signaling pathway, which is known to

repair neuronal damage in the brain.

Aging: Preliminary studies with resveratrol, a possible SIRT1 activator, have led some scientists to

speculate that resveratrol may extend lifespan. Further experiments conducted by Rafael de Cabo et al.

showed that resveratrol-mimicking drugs such as SRT1720 could extend the lifespan of obese mice by 44%.

Comparable molecules are now undergoing clinical trials in humans.

Dr. Asha Rani N, Assistant Professor, Biochemistry

Visfatin

Visfatin is a newly discovered adipocyte hormone with a direct relationship between plasma visfatin level

and type 2 diabetes mellitus. Also known as Nicotinamide phosphoribosyltransferase (NAmPRTase or

Nampt) as pre-B-cell colony-enhancing factor 1 (PBEF1) .It is an enzyme that in humans is encoded by the

PBEF1 gene. This protein has also been reported to be a cytokine (PBEF) that promotes B cell maturation

and inhibits neutrophil apoptosis.

NAmPRTase catalyzes the following chemical reaction:

Nicotinamide D-ribonucleotide + diphosphate -------Nicotinamide + 5-phospho-alpha-D-ribose 1-

diphosphate

This enzyme belongs to the family of glycosyltransferases, to be specific, the pentosyltransferases. This

enzyme participates in nicotinate and nicotinamide metabolism.

Function: The protein is an adipokine that is localized to the bloodstream It is an endocrine, autocrine as

well as paracrine peptide with many functions including enhancement of cell proliferation, biosynthesis of

nicotinamide mono- and dinucleotide and hypoglycaemic effect, including the promotion of vascular smooth

muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptor and has

insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. Visfatin binds to the

insulin receptor at a site distinct from that of insulin and causes hypoglycaemia by reducing glucose release

from liver cells and stimulating glucose utilization in adipocytes and myocytes. The protein is highly

expressed in visceral fat and serum levels of the protein correlate with obesity. This has also been identified

in many tissues and organs including the brain, kidney, lung, spleen and testis but preferentially expressed in

visceral adipose tissue Visfatin is up regulated by hypoxia, inflammation and hyperglycaemia and

downregulated by insulin, somatostatin and statins.

Dr.Prathibha K Postgraduate, Biochemistry

Fun and Learn

Biomed Crossword (Crossword on biochemical basis of diseases)

1

2 3

4 5

6 7

8 9

10

11 12 13

14 15

16 17

18

19 20 21

22

23

24

Across 1. X-linked Mucopolysacchroidosis (7)

7. Disease due to trinucleotide CAG expansion (6)

8. A disease common in hilly areas (6)

11. Also called as Forbe’s disease (5)

12. An underlying disease for all organ complications (8)

16. A disease with four D’s (8)

18. After the age of 40 years, you need to watch for this

disease (5)

20. ___ syndrome in which there is hypoglycaemia and

dicarboxylic aciduria in infants (4) (Abbreviation)

22. A disease due to protein misfolding (5)

23. A disease with burnt sugar urine (4) (Abbreviation)

24. Accumulation of GM2 occurs in this disease (3,5)

Down 2. ___ syndrome with trisomy 18

3. First disease with gene therapy (4)

(Abbreviation)

4. Many great personalities Newton,

Darwin etc suffered from this disease

(4)

5. A disease which is pronoun for

women (4)

6. A disease with charlie chaplin gait

(14)

9. Phosphofructokinase deficiency

disease (6)

10. A group of sexually transmitted

diseases (3)

13. Limeys did not suffer from this

disease (6)

14. β- Glucoronidase deficiency (4)

15. A primary dyslipoproteinemis

with low HDL (7)

16. Nutritional disorders (3)

(Abbreviation)

17. Dietary consumption of

methylated fatty acids leads to this

neurological disorder (7)

19. _______ eye disease (4)

21. About 20 % inmates of lunatic

asylum may have this disease (3)

(Abbreviation)

By Dr Aliya Nusrath

Prof and HOD, Biochemistry. Answers will be given in next issue {Answers of previous issue Across: 2.Collgen 7.Uracil. 9. BAL 10 Page 11.ETC 12.Ligase 13.Iodine 14.CO 15.Ryle

16.Laminin 19.Niacin 21.Leptin 23.STD

24.Peptide 25.Orotate 27.Starch 29.RE

30.Myosin 31.Phenol Down: 1.Fiber 2.Calcium 3.Lipid 4.Arginine

5.Nucleotide 6.Sanger 8.Insulin 17.Acetone

18.Intron 19.NTP 20.Citrate 22.NSAIDs

26.Exon 27.SNP 2

QUOTE “Research is to see what everybody has seen and to think what nobody else has thought”.

Albert Szent-Gyorgyi.