Author: Renu Maurya

Glycolipids

Glycolipids

Q. 1 Glycerol  is  the  backbone  of  all  of  the following phospholipids EXCEPT
 A Phosphatidylethanolamine
 B Cardiolipin
 C Phosphatidylcholine
 D Sphingomyelin
Q. 1 Glycerol  is  the  backbone  of  all  of  the following phospholipids EXCEPT
 A Phosphatidylethanolamine
 B Cardiolipin
 C Phosphatidylcholine
 D Sphingomyelin
Ans. D

Explanation:

Sphingomyelin   = phosphorylcholine + ceramide

Ceramide            = fatty acid + sphingosine

Sphingosine        = condensing palmitic acid with a decarboxylated   serine   and   then   reducing   the product

Glycerol  never  is  involved  in  the  structure  of sphingomyelin. Phosphatidylethanolamine, cardiolipin, phosphatidylcholine, and phosphatidylinositol are synthesized using phosphatidic acid as the basic building block  Phosphatic acid  is  diacylglycerol with a phosphate  ester on carbon three; therefore, glycerol is the backbone of all of these compounds. FAQ Sphingomyelin :-

–  Membranous myelin sheath that surrounds nerve cell axons.

–    It is the only sphingolipid NOT derived from Glycerol.

–       Associated  with  increased  accumulation  in Niemann-Pick  Disease.


Q. 2

Which of the following occurs in the lipidosis known as Tay-Sachs disease?

 A

Synthesis of a specific ganglioside is excessive

 B

Xanthomas due to cholesterol deposition are observed

 C

Phosphoglycerides accumulate in the brain

 D

Ganglioside GM2 is not catabolized by lysosomal enzymes

Q. 2

Which of the following occurs in the lipidosis known as Tay-Sachs disease?

 A

Synthesis of a specific ganglioside is excessive

 B

Xanthomas due to cholesterol deposition are observed

 C

Phosphoglycerides accumulate in the brain

 D

Ganglioside GM2 is not catabolized by lysosomal enzymes

Ans. D

Explanation:

In the genetic disorder known as Tay-Sachs disease, ganglioside GM2 is not catabolized. As a consequence, the ganglioside concentration is elevated many times higher than normal. The functionally absent lysosomal enzyme is β-N- acetylhexosaminidase.

The elevated GM2 results in irreversible brain damage to infants, who usually die before the age of 3 years. Under normal conditions, this enzyme cleaves N- acetylgalactosamine from the oligosaccharide chain of this complex sphingolipid, allowing further catabolism to occur.

The cause of most lipidoses (lipid storage diseases) is similar.

That is, a defect in catabolism of gangliosides causes abnormal accumulation.

None of the other choices result in lipidotic disorders. 

Ref: Hopkin R., Grabowski G.A. (2012). Chapter 361. Lysosomal Storage Diseases. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

 


Q. 3

Glycosphingolipidis made up of:

 A

Glucose

 B

Fatty acids

 C

Sphingosine

 D

All Correct

Q. 3

Glycosphingolipidis made up of:

 A

Glucose

 B

Fatty acids

 C

Sphingosine

 D

All Correct

Ans. D

Explanation:

A, B, C i.e. Glucose, Sphingosine, Fatty acids

Glycosphingolipid = Ceramide (Sphingosine / amino alcohol + Fatty acid) + Mono/oligo saccharide like glucose, galactose. Ganglioside (acidic glycosphingolipid) = Ceramide + Oligosaccharide + NANA (N-acetylneuraminic acid or sialic acid)

 

–  Glyco-sphingolipid is made up of ceramide (which is a long chain fatty acid attached to amino group of sphingosine through an amide linkage i.e. = sphingosine/ amino alcohol + Fatty acid) attached directly to mono /oligo saccharide

(polar head) by an 0-glycosidic bond. Glycosphingolipids differ from sphingomyelin (phospho- sphingolipid) in that they do not contain phosphate (polar group); and differ from glycerophospholipids (phosphoglycerides) that they do not contain glycerol.

Ganglioside (acidic, negatively charged glyco-sphingolipid) contain sphingosine alcohol (4 sphingenine) 1 molecule, long chan fatty acid (1 mol), Oligosaccharide polar head and 1 or more residues of N- acetylneurminic acid (Neu 5 Ac), a sialic acid (often simply called sialic acid) giving it a negative charge, at termini. Ganglioside do not contain glycerol and phosphateQ.

Ceramide containing sphingosine amino alcohol is present in all sphingolipids (ie. phospho & glyco- sphingolipids)Q.



Q. 4

Which of the following is not a glycerosphingolipid?

 A

Lecithin

 B

Cardiolipin

 C

Plasmalogens

 D

Sphingomyelin

Q. 4

Which of the following is not a glycerosphingolipid?

 A

Lecithin

 B

Cardiolipin

 C

Plasmalogens

 D

Sphingomyelin

Ans. D

Explanation:

 

Phospholipids are :

  1. Glycerophospholipids (glycerol containing) :- Phosphatidylcholine (lecithin), phosphatidylethanolamine (cephaline), phosphatidylserine, phosphatidylinositol, plasmalogens, lysophospholipids, cardiolipin.
  2. Sphingophospholipids (sphingosine containing) :- Sphingomyeline

Quiz In Between



Glycolipids

GLYCOLIPIDS


GLYCOLIPIDS (GLYCOSPHINGOLIPIDS)

  • Glycosphingolipid = Sphingosine + long chain fatty acid + sugars
  • Glycolipids are synthesized in endoplasmic reticulum.
  • Glycosphingolipids are 4 types-

Cerebrosides– ( ceramide + monosaccharides)

  • Cerebroside= sphingoside + long chain fatty acid + glucose
  • Monosaccharides used is mostly glucose (glucocerebroside) or galactose (galactocerebroside).
  • Clinical Aspect- 
  1. Krabbe’s disease caused by deficiency of enzyme of ?- galactosidase (Galactocerebroside accumulates in brain).
  2. Gaucher’s disease caused by deficiency of ?- glucosidase (glucocerebrosidase)
  • Glucocerebroside (glucosylceramide) is accumulated in brain.
  1. Sulfatides– cerebroside + sulphate
  2. Globosides– ceramide + oligosaccharide
  3. Gangliosides
  • ceramide + oligosaccharide chain (glucose+galactose) + N- acetylneuromic acid (NANA)
  • Gangliosides= Sphingosine+ long chain fatty acid + oligosaccharide chain (glucose or galactose)+ NANA
  • Clinical Aspect-
  • Tay- Sach’s Disease– caused due to deficiency of hexosaminidase (alpha subunit)
  • Sandoff disease- caused due to deficiency of hexoaminidase (Beta subunit)

Exam Important

  • Glycosphingolipid = Sphingosine + long chain fatty acid + sugars
  • Glycolipids are synthesized in endoplasmic reticulum.
  • Glycosphingolipids are 4 types-

Cerebrosides– ( ceramide + monosaccharides)

  • Cerebroside= sphingoside + long chain fatty acid + glucose
  • Monosaccharides used is mostly glucose (glucocerebroside) or galactose (galactocerebroside).
  • Clinical Aspect-
  1. Krabbe’s disease caused by deficiency of enzyme of ?- galactosidase.
  2. Galactocerebroside accumulates in brain.
  3. Gaucher’s disease caused by deficiency of ?- glucosidase (glucocerebrosidase)
  4. Glucocerebroside (glucosylceramide) is accumulated in brain.
  5. Sulfatides– cerebroside + sulphate
  6. Globosides– ceramide + oligosaccharide
  7. Gangliosides
  • ceramide + oligosaccharide chain (glucose+galactose) + N- acetylneuromic acid (NANA)
  • Gangliosides= Sphingosine+ long chain fatty acid + oligosaccharide chain (glucose or galactose)+ NANA
  • Tay- Sach’s Disease– caused due to deficiency of hexosaminidase (alpha subunit) .
Don’t Forget to Solve all the previous Year Question asked on GLYCOLIPIDS

Module Below Start Quiz

Isoenzymes

ISOENZYMES

Q. 1

True about isoenzymes is:

 A

Same quaternary structure

 B

Same distribution in different organs

 C

Same enzyme classification with same umbers

 D

Catalyze the same reaction

Q. 1

True about isoenzymes is:

 A

Same quaternary structure

 B

Same distribution in different organs

 C

Same enzyme classification with same umbers

 D

Catalyze the same reaction

Ans. D

Explanation:

    • Isoenzymes are the multiple forms of the same enzyme in a single species that catalyze the same chemical reaction or reactions, but differ from each other structurally, electrophoretically and immunologically.
    • Though the same chemical reaction is catalyzed, the different isoenzymes may catalyze the same reaction at different rates.
    • Isoenzymes have different pH optimes, Km and V max values.
    • Isoenzymes may differ in their amino acid sequence and their quarternary structures.
    • The isoenzymes may have different properties also for e.g. LDH-4 and LDH-5 are easily destroyed by heat, whereas LDH-1 and LDH-2 are not, if heated upto 60°C. (Heat resistant).
    • Individual isoenzymes (isozymes) are distinguished and numbered on the basis of electrophoretic mobility, with the number 1 being assigned to that form having the highest mobility toward the anode, for e.g. LDH-1 has the highest mobility towards the anode and LDH-5 is the slowest.
    • Isoenzymes have different tissue distributions. Therefore the pattern of isoenzymes found in the plasma may serve as a means of identifying the site of tissue damage. Example of the diagnostic use of isoenzymes are the study of Lactate Dehydrogenase and Creatine Kinase.

Q. 2

True about isoenzymes is/are:

 A

Different km value

 B

Act on different substrate

 C

Same electrophoretic mobility

 D

All

Q. 2

True about isoenzymes is/are:

 A

Different km value

 B

Act on different substrate

 C

Same electrophoretic mobility

 D

All

Ans. A

Explanation:

  • Isozymes are the physically distinct forms of the same enzymes that catalyze the same reaction, and differ from each other structurally, electrophoretically and immunologically.
  • They differ in their physical properties because of genetically determined difference in amino acid sequence.
  • They are separated by electrophoresis as they have different electrophoretic mobility.
  • They have different Km value.
  • Isoenzyme of an oligomeric enzyme process differ in combination of its peptide protomer.

Q. 3

Which isoenzyme of LDH is seen in heart

 A

LDH 1

 B

LDH 2

 C

LDH 3

 D

LDH 4

Q. 3

Which isoenzyme of LDH is seen in heart

 A

LDH 1

 B

LDH 2

 C

LDH 3

 D

LDH 4

Ans. A

Explanation:

Ans. is ‘a’ i.e., LDH1

Quiz In Between


Q. 4

First enzyme to be raised in MI is ‑

 A

CPK-MB

 B

LDH

 C

Myoglobin

 D

Troponin-I

Q. 4

First enzyme to be raised in MI is ‑

 A

CPK-MB

 B

LDH

 C

Myoglobin

 D

Troponin-I

Ans. C

Explanation:

Ans. is ‘c’ i.e., Myoglobin 


Q. 5

Enzyme specificity is given by ‑

 A

Km

 B

Vrm„

 C

Both

 D

None

Q. 5

Enzyme specificity is given by ‑

 A

Km

 B

Vrm„

 C

Both

 D

None

Ans. A

Explanation:

Ans. is ‘a’ i.e., K. 

  • The Km of an enzyme is the concentration of the substrate that enables the enzyme to function at half maximum activity and is therefore a measure of the specificity of a substrate.for the enzyme” Clinical biochemistry
  • Actually enzyme specificity is not measured by Km alone.
  • It is measured by the ratio Kcat/Km which is a second order rate constant for the reaction between substrate and free enzyme.
  • This ratio is important, for it provides a direct measure of enzyme efficiency and specificity.
  • Note : Kcat is turnover number and measures the rate of the catalytic process.

Q. 6

Q10 in enzyme matches with ‑

 A

2

 B

4

 C

8

 D

10

Q. 6

Q10 in enzyme matches with ‑

 A

2

 B

4

 C

8

 D

10

Ans. A

Explanation:

Ans. is ‘a’ i.e., 2

  • Most enzyme show a 50-300% (average 200%) increase in reaction rate when the temperature is increased by 10°, and the ratio of rate constant at two temperatures 10° apart is usually between 1.5 to 4 (average 2) for most enzymes.
  • This value is termed as Q10.
  • “The rate of enzymatic reaction doubles with every 10° rise in temperature. “

Q. 7

Fastest acting enzyme ‑

 A

LDH

 B

Trypsin

 C

Catalase

 D

None

Q. 7

Fastest acting enzyme ‑

 A

LDH

 B

Trypsin

 C

Catalase

 D

None

Ans. C

Explanation:

Ans. is ‘c’ i.e., Catalase 

Measurement of enzyme activity

  • The activity of enzyme is measured in terms of the following :
  • Unit of enzyme activity : – By international agreement, one unit enzyme activity is defined as the amount causing transformation of 1.0 micro mole of substrate per minute at 25° C. It is usually expressed as mole of substrate disappeared or mole of product formed per minute.
  • Specific activity : – It refers to the number of enzyme units per milligram of protein. It is a measure of enzyme purity; higher the enzyme purity, more is the specific activity.
  • Turn over number : – This refers to the number of substrate molecules transformed per unit time by a single enzyme molecule (or by a single catalytic site), when the enzyme concentration alone is rate-limiting factor. Catalase has the highest turnover number and hence is the fastest active enzyme. Carbonic anydrase has the 2″ fastest turnover number; therefore, it is 2nd fastest active enzyme (after catalase). Lysozyme has the lowest turnover number and therefore is slowest acting.

Quiz In Between



Isoenzymes

ISOENZYMES


ISOENZYMES (ISOZYMES)

  • Isoenzymes are the physically distinct forms of the same enzyme.
  • Isoenzymes differ from each other structurally, electrophoretically and immunologically.
  • Isoenzymes possess quaternary structure and are made up of two or three different subunit (mutimeric).
  • Isoenzymes catalyze the same reaction and act on same substrate, but with different Km and Vmax values i.e. isozymes have different kinetics.

Plasma Enzymes-

  • Functional plasma enzymes- specific function in the plasma. E.g. Coagulation factors (thrombin), lipoprotein lipase, clotting factors.
  • Non functional enzymes- E.g. alkaline phosphatase, acid phosphatase, gamma glutamyl transpeptidase, LDH, Creatine kinase.

Lactate Dehydrogenase (LDH)

  • LDH with two subunits- H(heart) and M(muscle)
  • It has five isoenzymes.
Name of the isoenzyme Tissue location
LDH-1 Heart muscle
LDH-2 RBC
LDH-3 Brain
LDH-4 Liver and skeletal muscle
LDH-5 Liver and skeletal muscle
  • In MI, LDH1 is raised more than LDH2.
  • Normal LDH pattern on electrophoresis is LDH2 > LDHI > LDH 3 > LDH 4>LDH5
  • Increased in LDH level- pancreatitis.

Creatine Kinase (CK)

  • Three isoenzymes.
  • It is subunit M(myocardium) and B (Brain).
Name of isoenzyme Tissue localisation
CK-1 Brain
CK-2 Heart
CK-3 Skeletal Muscle

Alkaline Phosphatase (ALP)-

Isoenzyme Tissue Location
Alpha-1 ALP Epithelial cells of biliary canaculi
Alpha-2 heat liable ALP Hepatic cells
Alpha-2 heat stable ALP Placenta (Inhibited by Phenylalanine)
Pre beta ALP Osteoblast
Gamma ALP Intestinal cells
Leukocyte ALP Leukocytes
  • Raised activity of alkaline phosphatase is useful in diagnosis of bone and liver pathology.

 Transaminase-

  • Aspartate Transaminase- increase in myocardium.
  • Mitochondrial isoenzyme present in liver.
  • Alanine Transaminase (ALT)-  mainly in liver and entirely in Cytoplasm. 

Protease-

  • Serine Proteasesserine residue at the active site(serine, histidine, aspirate).
  • E.g.- Trypsin, chymotrypsin, elastase (catalytic traid)
  • Inhibited by disopropylphosphofluridate binds covalently to serine residue.
  • Activated in intestine by proteolytic activation.

Carboxyl or acid Proteases-

  • Most important carboxyl proteases is Pepsin.

Exam Important

  1. Isoenzymes differ from each other structurally, electrophoretically and immunologically.
  2. Isoenzymes possess quaternary structure and are made up of two or three different subunit (mutimeric).
  3. Functional plasma enzymes- specific function in the plasma.- E.g. Coagulation factors (thrombin), lipoprotein lipase, clotting factors.
  4. Non functional enzymes  E.g. alkaline phosphatase, acid phosphatase, gamma glutamyl transpeptidase, LDH, Creatine kinase.
  5.  LDH has five isoenzymes.
Name of the isoenzyme Tissue location
LDH-1 Heart muscle
LDH-2 RBC
LDH-3 Brain
LDH-4 Liver and skeletal muscle
LDH-5 Liver and skeletal muscle

 6. In MI, LDH1 is raised more than LDH2.

 7. Creatine Kinase (CK)- Three isoenzymes.

CK-1 Brain
CK-2 Heart

 8. ALP found in liver, bone, kidney, intestinal mucosa and placenta.

9. Serine Proteasesserine residue at the active site(serine, histidine, aspirate).

10. Serine proteases- E.g.- Trypsin, chymotrypsin, elastase (Catalytic triad).

11. Serine proteases activated in intestine by proteolytic activation.

12.  Most important carboxyl proteases is Pepsin.

Don’t Forget to Solve all the previous Year Question asked on ISOENZYMES

Module Below Start Quiz

Histones

Histones

Q. 1

Histone acetylation causes?

 A >Increased Heterochromatin formation
 B >Increased Euchromatin formation
 C >Methylation of cystine
 D >DNA replication
Q. 1

Histone acetylation causes?

 A >Increased Heterochromatin formation
 B >Increased Euchromatin formation
 C >Methylation of cystine
 D >DNA replication
Ans. B

Explanation:

Increased Euchromatin formation [Ref: Lippincott’s Biochemistery 3/e p406, 420; Harper biochemistry 28/e p.315]

Histone acetylation promotes Euchromatin formation (transcriptionally active DNA).

Deacetylation and methylation promotes Heterochromatin formation (transcriptionally inactive DNA).

  • There are five classes of histones, designated HI, H2A, H2B, H3, and H4. These small proteins are positively charged at physiologic pH as a result of their high content of lysine and arginine. Because of their positive charge, they form ionic bonds with negatively charged DNA. Histones help in condensation of DNA into chromosomes.
  • Two molecules each of H2A, H2B, H3, and H4 form the structural core of the individual nucleosome “beads.” Around which a segment of the DNA double helix is wound nearly twice. (Histone HI, is not found in the nucleosome core, but instead binds to the linker DNA chain between the nucleosome beads.). Nucleosomes are further arranged into increasingly more complex structures that organize and condense the long DNA molecules into chromosomes.
  • These histone proteins can undergo reversible modifications at their N-terminal end (like acetylation, methylation or phosphorylation). These modifications help in regulation of gene expression.
  • Acetylation of the lysine residues at the N terminus of histone proteins removes positive charge on the lysine and thereby decreases the interaction of the histone with the negatively charged DNA. As a result, the condensed chromatin is transformed into a more relaxed structure allowing transcription factors to access specific regions on the DNA. Deacetylation restores the positive charge, causing stronger interactions between histones and DNA.
  • Thus histone acetylation enhances transcription while histone deacetylation represses transcription.
  • Relaxed, transcriptionally active DNA is referred to as euchromatin. More condensed, inactive DNA is referred to as heterochromatin.
  • Histone acetylation is catalyzed by histone acetyltransferases (HATS) and histone deacetylation is catalyzed by histone deacetylases (denoted by HDs or HDACs).
  • Another difference noted between transcriptionally active and inactive chromatin is the extent of methylation of cytosine bases in CG-rich regions (CG islands) of many genes. It has been observed that transcriptionally active genes are less methylated (hypomethylated) than their inactive counterparts.
  • Thus formation of euchromatin is promoted by acetylationand formation of heterochromatin is promoted by deacetylation and methylation. The action of methylation is indirect and has no effect upon charge.

Q. 2

Acetylation of histones results in which of the following modification?

 A

Increased Heterochromatin formation

 B

Increased mRNA production

 C

Activate Deacetylases

 D

Arginine Methylation

Q. 2

Acetylation of histones results in which of the following modification?

 A

Increased Heterochromatin formation

 B

Increased mRNA production

 C

Activate Deacetylases

 D

Arginine Methylation

Ans. B

Explanation:

Pretranscriptional control refers to the carefully controlled and selective unwinding of chromatin to facilitate gene expression.

It is known that modification of histones is functionally important in this process.

Enzymatic attachment of an acetyl group to certain amino acids in histones is critical – Acetylation of histones.

The acetylation of histones affects the charge interactions with DNA, resulting in unwinding of DNA at that specific location, and thereby facilitates subsequent steps required to generate nascent mRNA.

Conversely, deacetylation of histones can result in rewinding of chromatin and inhibition of gene expression. This modification of histones is carried out by a large family of enzymes termed histone acetyl transferases (HATs) and histone deacetylases (HDACs)

Why is this topic important and frequently asked?

1. Cardiovascular biology: E.g. Experimental studies in mice lacking specific HATs or HDACs can profoundly alter processes such as blood vessel development or cardiac hypertrophy.


Because acetylation and deacetylation are enzymatic processes, they are amenable to pharmacologic manipulation. Indeed, agents such as trichostatin A have been shown to ameliorate cardiac hypertrophy in rodents.

2. Chromatin modification: Acetylation is perhaps the most well-studied chromatin modification so far. However others such as lysine/arginine methylation, serine phosphorylation, and ubiquitination are also likely to be important areas from both a scientific and therapeutic perspective for the future.

Ref: Walsh R.A., Jain M.K., Proweller A. (2011). Chapter 6. Principles of Molecular Cardiology. In V. Fuster, R.A. Walsh, R.A. Harrington (Eds), Hurst’s The Heart, 13e.


Q. 3

Nucleoside is made up of:

1. Pyrimidine
2. Histone
3. Sugar
4. Purine
5. Phosphate

 A

1,2 & 3

 B

1,3 & 4

 C

1,3 & 5

 D

2,3 & 4

Q. 3

Nucleoside is made up of:

1. Pyrimidine
2. Histone
3. Sugar
4. Purine
5. Phosphate

 A

1,2 & 3

 B

1,3 & 4

 C

1,3 & 5

 D

2,3 & 4

Ans. B

Explanation:

“The nucleoside is composed of purine purine or pyrimidine base linked to either D-ribose (in RNA) or D-2- deoxyribose (in DNA)”

“The nuclear DNA is found bounded to basic proteins called histones”.
Nucleotides
  • Nucleotides are nucleoside +P
  • The Phosphodiester bond between the nucleotides is formed mainly between 3’OH group of sugar of one nucleotide to 3’OH group of sugar of another nucleotide.

 

Ref: Harper 27/e, Page 297; Chatterjee & shinde 7/e, Page 206-07.

Quiz In Between


Q. 4

True about Histone protein:

 A

Ribonucleoprotein

 B

Present inside the nucleus

 C

Acidic

 D

None

Q. 4

True about Histone protein:

 A

Ribonucleoprotein

 B

Present inside the nucleus

 C

Acidic

 D

None

Ans. B

Explanation:

B i.e. Present inside the nucleus;


Q. 5

Histone acetylation causes?

 A

Increased Heterochromatin formation

 B

Increased Euchromatin formation

 C

Methylation of cystine

 D

DNA replication

Q. 5

Histone acetylation causes?

 A

Increased Heterochromatin formation

 B

Increased Euchromatin formation

 C

Methylation of cystine

 D

DNA replication

Ans. B

Explanation:

B i.e. Increased Euchromatin formation


Q. 6

Histone has post – translational modification by all/except.

 A

Acylation

 B

Methylation

 C

Phosphorylation

 D

Glycosylation

Q. 6

Histone has post – translational modification by all/except.

 A

Acylation

 B

Methylation

 C

Phosphorylation

 D

Glycosylation

Ans. D

Explanation:

D i.e. Glycosylation

Quiz In Between



Histones

HISTONES


Histones

  • Most abundant chromatin Protein.
  • Histones are divided into-
  1. Core Histone
  2. Linker Histone
  • 5 classes- H1, H2A, H2B (Lysine), H3 and H4 (arginine).
  • Linker histone- is loosely bound to nucleosome.
  • Modifications-
  1. Acetylation of H3 & H4
  2. Acetylation of histones associated with chromosomal assembly during DNA replication.
  3. Phosphorylation of H1 is associated with condensation of chromosome during replication.
  4. Methylation correlated with activation or repression of gene transcription.
  • Chromatins are of two types-
  • Euchromatin- Transcriptionally active chromatin and is uncondensed. Chromatins are less stained.
  • Heterochromatin- Transcriptionally inactive, chromatin stains densely, chromatin densely packed. 2 types-
  1.  Constitutive- seen in centromere and chromosomal ends of the telomere.
  2.  Facultative
  • Chromosomes-
  •  In humans, there are 23 pairs of chromosomes.
  •  The position of centromere is the characteristic mark for specific chromosome.
  •  The centromere is AT rich region.
  • Total number of chromosome in humans is 46 (23 pairs).
  • The number of base pairs in haploid set of chromosome is 3.0 x 1O9 (3 billion bp)
  • Percentage of exons in human genome is approximately 1.14% (1.5-2%)
  • The number of protein coding genes in human genome is 20,687.
  • The genes account for 10-15% of DNA.

Exam Important

  • Total number of chromosome in humans is 46 (23 pairs).
  • The number of base pairs in haploid set of chromosome is 3.0 x 1O9 (3 billion bp)
  • Percentage of exons in human genome is approximately 1.14% (1.5-2%)
  • The number of protein coding genes in human genome is 20,687.
  • The genes account for 10-15% of DNA.
  • Euchromatin is transcriptionally active and heterochromatin is transcriptionally inactive.
  • For euchromatin, chromatin is less densely packed.
  • For heterochromatin, chromatin is densely packed.
Don’t Forget to Solve all the previous Year Question asked on HISTONES

Module Below Start Quiz

Organization of DNA in the cell

Organization of DNA in the cell

Q. 1

Total number of base pairs in human haploid set of chromosome

 A

3 million

 B

3 billion

 C

33 billion

 D

5 million

Q. 1

Total number of base pairs in human haploid set of chromosome

 A

3 million

 B

3 billion

 C

33 billion

 D

5 million

Ans. B

Explanation:

  • Humanhaploid genome of each cell consist of (3*109 ) bp (3 billion bp)
  • Current estimates predict 20,687 protein coding genes
  •  Exome constitutes 7.74% of genome
  • SNPs estimated is 10 million.

Q. 2

Proteins seen in chromosomes are called

 A

Nucleotides

 B

Histones

 C

Apoproteins

 D

Glycoproteins

Q. 2

Proteins seen in chromosomes are called

 A

Nucleotides

 B

Histones

 C

Apoproteins

 D

Glycoproteins

Ans. B

Explanation:

Histones are the most abundant histone proteins.

Quiz In Between



Organization of DNA in the cell

ORGANIZATION OF DNA IN THE CELL


Organization of DNA in the cell 

  • Genome in the prokaryotes is loosely packed.
  • In eukaryotes, DNA is well organized inside the nucleus.
  • Levels of organization of DNA is– DNA Double helix
  •  Nucleosomes form of chromatin are of-

10nm chromatin fibril

  • In eukaryotics, Nucleosomes are  separated   by spacer DNA to which histone H1 is attached This continuous string of nucleosomes, representing beads-on-a string form of chromatin is termed as 10 nm fiber.
  • DNA double helix is wrapped nearly twice (exactly 1.75 times) over   a histone octamer in left-handed helix to form a disk like structure.

30nm chromatin fibril–  (Solenoid)

  • Groups of nucleosome form’DNA fibril’
  • 6 such DNA fibrils form 30 nm chromatin fibril.
  • The double stranded DNA wraps twice around a histones.
  • A nucleosome associated with histone H1 is called chromatosome.
  • A series of nucleosome (beads on a string) is called as polynucelosome or chromatin.
  • DNA molecule is amphipathic.
  • At physiological pH, DNA is negatively charged (Acidic).

Exam Important

  • Chromatin is unfolded and uncondensed.
  • Chromatin and chromosome are made up of DNA and non-histone proteins.
  • At the physiological pH, DNA is negatively charged because of phosphate group.
  • DNA molecule is an amphipathic.
Don’t Forget to Solve all the previous Year Question asked on ORGANIZATION OF DNA IN THE CELL

Module Below Start Quiz

Metabolism Of Purine

METABOLISM OF PURINE

Q. 1 The purines salvage pathway is for:
 A Hypoxanthine and Xanthine
 B Hypoxanthine andAdenine
 C Adenine and Guanine
 D Xanthine and Guanine
Q. 1 The purines salvage pathway is for:
 A Hypoxanthine and Xanthine
 B Hypoxanthine andAdenine
 C Adenine and Guanine
 D Xanthine and Guanine
Ans. B

Explanation:

Hypoxanthine andAdenine


Q. 2

In humans, the end product of purine metabolism is uric acid. End product of purine metabolism in non-primate mammals is:

 A

Uric acid

 B

Ammonia

 C

Urea

 D

Allantoin

Q. 2

In humans, the end product of purine metabolism is uric acid. End product of purine metabolism in non-primate mammals is:

 A

Uric acid

 B

Ammonia

 C

Urea

 D

Allantoin

Ans. D

Explanation:

Humans convert adenosine and guanosine to uric acid. Adenosine is first converted to inosine by adenosine deaminase. In mammals other than higher primates, uricase converts uric acid to the water-soluble product allantoin. However, since humans lack uricase, the end product of purine catabolism in humans is uric acid.  

Ref: Rodwell V.W. (2011). Chapter 33. Metabolism of Purine & Pyrimidine Nucleotides. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper’s Illustrated Biochemistry, 29e.  

Q. 3

Nucleoside is made up of:

1. Pyrimidine
2. Histone
3. Sugar
4. Purine
5. Phosphate

 A

1,2 & 3

 B

1,3 & 4

 C

1,3 & 5

 D

2,3 & 4

Q. 3

Nucleoside is made up of:

1. Pyrimidine
2. Histone
3. Sugar
4. Purine
5. Phosphate

 A

1,2 & 3

 B

1,3 & 4

 C

1,3 & 5

 D

2,3 & 4

Ans. B

Explanation:

“The nucleoside is composed of purine purine or pyrimidine base linked to either D-ribose (in RNA) or D-2- deoxyribose (in DNA)”

“The nuclear DNA is found bounded to basic proteins called histones”.
Nucleotides
  • Nucleotides are nucleoside +P
  • The Phosphodiester bond between the nucleotides is formed mainly between 3’OH group of sugar of one nucleotide to 3’OH group of sugar of another nucleotide.

 

Ref: Harper 27/e, Page 297; Chatterjee & shinde 7/e, Page 206-07.

Quiz In Between


Q. 4

Which among the following are the substrates needed for purine salvage pathway?

 A

Hypoxanthine and Xanthine

 B

Hypoxanthine and Adenine

 C

Adenine and Guanine

 D

Xanthine and Guanine

Q. 4

Which among the following are the substrates needed for purine salvage pathway?

 A

Hypoxanthine and Xanthine

 B

Hypoxanthine and Adenine

 C

Adenine and Guanine

 D

Xanthine and Guanine

Ans. B

Explanation:

Conversion of purines, their ribonucleosides, and their deoxyribonucleosides to mononucleotides involves “salvage reactions”.
The more important mechanism involves phosphoribosylation by PRPP of a free purine (Pu) to form a purine 5′-mononucleotide (Pu-RP). Phosphoryl transfer from ATP, catalyzed by adenosine- and hypoxanthine-phosphoribosyl transferases, converts adenine, hypoxanthine, and guanine to their mononucleotides. 
 
A second salvage mechanism involves phosphoryl transfer from ATP to a purine ribonucleoside. Phosphorylation of the purine nucleotides, catalyzed by adenosine kinase, converts adenosine and deoxyadenosine to AMP and dAMP. Similarly, deoxycytidine kinase phosphorylates deoxycytidine and 2′-deoxyguanosine, forming dCMP and dGMP.
 
Ref: Rodwell V.W. (2011). Chapter 33. Metabolism of Purine & Pyrimidine Nucleotides. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper’s Illustrated Biochemistry, 29e.

 


Q. 5

End product of purine metabolism in non-primate mammals is:

 A

Uric acid

 B

Ammonia

 C

Urea

 D

Allantoin

Q. 5

End product of purine metabolism in non-primate mammals is:

 A

Uric acid

 B

Ammonia

 C

Urea

 D

Allantoin

Ans. D

Explanation:

D i.e. Allantoin


Q. 6

Which of the following RNA has abnormal purine bases:

 A

t-RNA

 B

m-RNA

 C

r-RNA

 D

16S RNA

Q. 6

Which of the following RNA has abnormal purine bases:

 A

t-RNA

 B

m-RNA

 C

r-RNA

 D

16S RNA

Ans. A

Explanation:

A i.e. tRNA

Quiz In Between


Q. 7

Amino acid which contributes to biosynthesis of purine ribonucleotide are all except:    

 A

Aspartate

 B

Histidine

 C

Glutamine

 D

Glycine

Q. 7

Amino acid which contributes to biosynthesis of purine ribonucleotide are all except:    

 A

Aspartate

 B

Histidine

 C

Glutamine

 D

Glycine

Ans. B

Explanation:

 

Biosynthesis of purine

  • N1 of purine is derived from amino group of aspartate
  • N3 and N9 are obtained from amide group of glutamine
  • C4, C5 and N7 of the purine ring of nucleotides are contributed by glycine



Q. 8

Final product of purine metabolism is:

 A

Uric acid

 B

Creatinine

 C

Xanthine

 D

Phoshphates

Q. 8

Final product of purine metabolism is:

 A

Uric acid

 B

Creatinine

 C

Xanthine

 D

Phoshphates

Ans. A

Explanation:

 

Nucleotides are derived from biosynthetic precursors of carbohydrate and amino acid metabolism, and from ammonia and carbon dioxide.

The liver is the major organ of de novo synthesis of all four nucleotides.

Degradation in humans, however, is only complete for pyrimidines (C, T, U), but not purines (G, A), which are excreted from the body in form of uric acid



Q. 9

Nitrogen-9 of purine ring is provided by ‑

 A

Glycine

 B

Aspartate

 C

Glutamine

 D

CO2

Q. 9

Nitrogen-9 of purine ring is provided by ‑

 A

Glycine

 B

Aspartate

 C

Glutamine

 D

CO2

Ans. C

Explanation:

 

In de novo synthesis, purine ring is formed from variety of precursors is assembled on ribose-5-phosphate. Precursors for de novo synthesis are –

i)      Glycine provides C4, C5 and N7

ii)     Aspartate provides N1

iii)    Glutamine provides N3 and N9

iv)   Tetrahydrofolate derivatives furnish C2 and C8

v)    Carbon dioxide provides C6

Quiz In Between


Q. 10

First product of purine metabolism

 A

Uric acid

 B

Xanthine

 C

P-alanine

 D

CO2

Q. 10

First product of purine metabolism

 A

Uric acid

 B

Xanthine

 C

P-alanine

 D

CO2

Ans. B

Explanation:

 

  • Humans catabolize purines to uric acid.
  • But, first purines are catabolized to xanthine, which is further catabolized to purine.

Q. 11

First purine nucleotide, which is synthesized in purine biosynthesis ‑

 A

AMP

 B

GMP

 C

IMP

 D

UMP

Q. 11

First purine nucleotide, which is synthesized in purine biosynthesis ‑

 A

AMP

 B

GMP

 C

IMP

 D

UMP

Ans. C

Explanation:

 

The biosynthesis of purine begins with ribose-5-phosphate, derived from pentose phosphate pathway (PPP).

First intermediate formed in this pathway, 5-phosphoribosyl-pyrophosphate (PRPP), is also an intermediate in purine salvage pathway.


Q. 12

Salvage pathway of purine biosynthesis is important for ‑

 A

Liver

 B

RBCs

 C

Kidney

 D

Lung

Q. 12

Salvage pathway of purine biosynthesis is important for ‑

 A

Liver

 B

RBCs

 C

Kidney

 D

Lung

Ans. B

Explanation:

 

Purine nucleotide synthesis occurs by two pathways :

1.De novo synthesis

2.Salvage pathway

Liver is the major site of purine nucleotide biosynthesis (de novo).

Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymor­phonuclear leukocytes.

These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.

Quiz In Between


Q. 13

Purine metabolism produces –

 A

β – alanine

 B

NH3

 C

CO2

 D

Uric acid

Q. 13

Purine metabolism produces –

 A

β – alanine

 B

NH3

 C

CO2

 D

Uric acid

Ans. D

Explanation:

Ans. is ‘d’ i.e., Uric acid


Q. 14

PRPP glutamyl amidotransferase is increased to increase purine synthesis in ‑

 A

Liver

 B

RBC

 C

Brain

 D

Polymorphs

Q. 14

PRPP glutamyl amidotransferase is increased to increase purine synthesis in ‑

 A

Liver

 B

RBC

 C

Brain

 D

Polymorphs

Ans. A

Explanation:

 

PRPP glutamyl amidotransferase is one of the rate limiting enzyme in de novo synthesis of purines. o The de novo synthesis of purines is most active in liver.

Brain, RBCs (erythrocytes) and polymorphonuclear leokocytes (polymorphs) cannot synthesize purine nucleotides by de novo pathway.

Biosynthesis of purine neucleotides

Two important purine nucleotides are synthesized : (i) adenosine monophosphate (AMP) and (ii) guanosine monophosphate (GMP). Then AMP and GMP are converted to other purine nucleotides like ADP, ATP, GDP, GTP etc. Purine nucleotides can be synthesized by two pathways – (I) De novo synthesis and (2) Salvage pathway.

De novo pathway (De novo synthesis)

In de novo pathway, the purine nucleotides are synthesized from amphibolic intermediates. Amphibolic intermediates are the intermediary metabolites of amphibolic pathways (eg. citric acid cycle) which have dual purposes, i e. they serve in catabolism as well as in anabolism.

In de novo synthesis, purine ring is formed from variety of precursors is assembled on ribose-5-phosphate. Precursors for de novo synthesis are

i)  Glycine provides C4 C5 and N7

ii)  Aspartate provides NI

iii)  Glutamine provides N3 and N9

iv)  Tetrahydrofolate derivatives furnish C2 and Cs

v)  Carbon dioxide provides C6


Q. 15

Salvage pathway of purine nucleotide synthesis are used by all except ‑

 A

Brain

 B

Liver

 C

RBC

 D

Leukocytes

Q. 15

Salvage pathway of purine nucleotide synthesis are used by all except ‑

 A

Brain

 B

Liver

 C

RBC

 D

Leukocytes

Ans. B

Explanation:

 

Purine nucleotide synthesis occurs by two pathways :-

1.De novo synthesis

2.Salvage pathway

Liver is the major site of purine nucleotide biosynthesis (de novo).

Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymorphonuclear leukocytes.

These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.

Quiz In Between


Q. 16

Salvage pathway of purine nucleotide synthesis are used by all except ‑

 A

Brain

 B

Liver

 C

RBC

 D

Leukocytes

Q. 16

Salvage pathway of purine nucleotide synthesis are used by all except ‑

 A

Brain

 B

Liver

 C

RBC

 D

Leukocytes

Ans. B

Explanation:

Ans. is ‘b’ i.e., Liver

  • Purine nucleotide synthesis occurs by two pathways :
  • De novo synthesis
  • Salvage pathway
  • Liver is the major site of purine nucleotide biosynthesis (de novo).
  • Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymorphonuclear leukocytes.
  • These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.

Q. 17

In humans, end product of purine metabolism 

 A

Allantoin

 B

Uric acid

 C

CO2

 D

None

Q. 17

In humans, end product of purine metabolism 

 A

Allantoin

 B

Uric acid

 C

CO2

 D

None

Ans. B

Explanation:

Ans. is ‘b’ i.e., Uric acid


Q. 18

Salvage purine synthesis refers to ‑

 A

Synthesis of purine from ribose-5-phosphate

 B

Synthesis of purine from pyrimidine

 C

Synthesis of purine nucleotides from purine bases

 D

None of the above

Q. 18

Salvage purine synthesis refers to ‑

 A

Synthesis of purine from ribose-5-phosphate

 B

Synthesis of purine from pyrimidine

 C

Synthesis of purine nucleotides from purine bases

 D

None of the above

Ans. C

Explanation:

Ans. is ‘c’ i.e., Synthesis of purine nucleotides from purine bases

  • Two important purine nucleotides are synthesized : (i) adenosine monophosphate (AMP) and (ii) guanosine monophosphate (GMP). Then AMP and GMP are converted to other purine nucleotides like ADP, ATP, GDP, GTP etc. Purine nucleotides can be synthesized by two pathways – (1) De novo synthesis and (2) Salvage pathway. De novo pathway (De novo synthesis)
  • In de novo pathway, the purine nucleotides are synthesized from amphibolic intermediates. Amphibolic intermediates are the intermediary metabolites of amphibolic pathways (eg. citric acid cycle) which have dual purposes, i e. they serve in catabolism as well as in anabolism.
  • In de novo synthesis, purine ring is formed from variety of precursors is assembled on ribose-5-phosphate. Precursors for de novo synthesis are ‑
  1. Glycine provides Ca, C5 and N7
  2. Aspartate provides N,
  3. Glutamine provides N3 and N9
  4. Tetrahydrofolate derivatives furnish C2 and C8
  5. Carbon dioxide provides Co

Salvage pathway of purine nucleotide synthesis

  • Free purine bases (adenine, guanine and hypoxanthine) and purine nucleosides are formed in cells during the metabolic degradation of nucleic acids and nucleotides.
  • These free purine bases and purine nucleosides are reused in the formation of purine nucleotides. 
  • This is called salvage pathway (salvage means property saved from loss).
  • Salvage synthesis requires far less energy than de novo synthesis.

Quiz In Between



Metabolism Of Purine

METABOLISM OF PURINE


METABOLISM OF PURINE

  • Purine nucleotides are synthesized-
  1. Adenosine monophosphate (AMP)
  2. Guanosine monophosphate (GMP)
  • Purine nucleotides synthesized by 2 pathways-
  1. De novo synthesis
  2. Salvage pathway

De novo synthesis

  • It is synthesis in liver.
  • It takes place in cytoplasm.
  • Precursors for de novo synthesis are –
  1. Glycine provides C4, C5 and N7
  2. Aspartate provides N1
  3. Glutamine provides N3 and N9
  4. Tetrahydrofolate derivatives furnish C2 and C8
  5. Carbon dioxide provides C6
  • IMP (also called inosinic acid) is the first purine nucleotide, which is synthesized as the precursor of AMP (also called adenylic acid) and GMP (also called guanylic acid).
  • The enzyme PRPP glutamyl amidotransferase is controlled by feedback inhibition of nucleotides.
  • The rate limiting step of de novo Purine Synthesis is PRPP Glutamyl amidotransferase.

Salvage pathway-

  • Free purine bases (adenine, guanine and hypoxanthine) and purine nucleosides are formed in cells during the metabolic degradation of nucleic acids and nucleotides. These free purine           bases and purine nucleosides are reused in the formation of purine nucleotides. This is called salvage pathway

Catabolism of Purine Metabolism- (Degradation)

  • Adenine nucleotides catabolism- liver, heart muscle, Skeletal muscle, GIT mucosa
  • Guanine nucleotides catabolism- liver, spleen, kidney, pancreas, GIT mucosa.
  • Human catabolises purine to uric acid.
  • First metabolic product of purines is Xanthine.
  • In higher primates, Allantoin by enzyme uricase is the end product.

Disorders of Purine Metabolism-

  • Gout
  • Lesch- Nyhan Syndrome
  • Adenosine deaminase deficiency
  • Purine nucleoside phophorylase deficiency

Exam Important

  • First Nucleotide formed in Purine Synthesis-lnosine Mono Phosphate (lMP)
  • Liver is the major site of nucleotide biosynthesis.
  • Tissues which cannot synthesis purine nucleotides by de nevo pathway are- brain, erythrocytes and leuckocytes.
Don’t Forget to Solve all the previous Year Question asked on METABOLISM OF PURINE

Module Below Start Quiz

Malcare WordPress Security