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RNA Polymerase (RNAP)

RNA Polymerase (RNAP)


RNA  Polymerase (RNAP)

  1. RNA polymerase (ribonucleic acid polymerase), both abbreviated RNAP or RNApol, official name DNA-directed RNA polymerase, is a member of a family of enzymes that are essential to life.
  2. RNAP locally opens the double-stranded DNA (usually about four turns of the double helix) so that one strand of the exposed nucleotides can be used as a template for the synthesis of RNA, a process called transcription.
  • They  are  DNA dependent  RNA Polymerase.
  • No primer is  needed  in  RNAP
  • No proofreading  activity in  RNAP.
  • Prokaryotic  RNA polymerase  is of only one type.
  • There  are three  types  of Eukaryotic  RNA Polymerase,  RNA  Polymerase  I, II and III.
  • Bacterial RNAP enzyme contains two alpha, two beta subunits, one omega subunit, and one sigma factor and two zinc molecules.
  • RNAP type II or Bis the main enzyme synthesizing mRNAs. It is inhibited by alpha-amanitin.
  • Phosphorylation activates RNAP II.
  • RNAP type I or A is responsible for the synthesis of Rrna (ribosomal); it is not inhibited by amanitin.
  • RNAP type III or C is responsible for the production of tRNA; it is moderately sensitive to amanitin.
  • RNAP type III catalyzes the synthesis of flRNA, small nuclear RNA (sz-RNA) and miRNA
  • Sigma factor enables the holoenzyme (RNA polymerase) to recognize and bind to The promoter sequence. Different sigma (σ) factors recognize the different group of genes
  • Alpha-amanitin inhibits RNA  polymerase  II of eukaryotes.
  • Rifampicin inhibits b-subunit of RNA  polymerase.
  • RNA polymerase (holoenzyme)= core enzyme+ sigma subunit
  • RNA  polymerase  holoenzyme requires:
  1. A template of ds/ss DNA
  2. Four ribonucleotide triphosphates GTP, UTP, ATP, CTP
  3. Mg” or Mn”
  • RNA primers are required for DNA replication, not for transcription.
  • RNA  polymerase is The major enzyme involved in transcription. 

Exam Important

  • They  are  DNA dependent  RNA Polymerase.
  • No primer is  needed  in  RNAP
  • No proofreading  activity in  RNAP.
  • Prokaryotic  RNA polymerase  is of only one type.
  • There  are three  types  of Eukaryotic  RNA Polymerase,  RNA  Polymerase  I, II and III.
  • Bacterial RNAP enzyme contains two alpha, two beta subunits, one omega subunit, and one sigma factor and two zinc molecules.
  • RNAP type II or Bis the main enzyme synthesizing mRNAs. It is inhibited by alpha-amanitin.
  • Phosphorylation activates RNAP II.
  • RNAP type I or A is responsible for the synthesis of Rrna (ribosomal); it is not inhibited by amanitin.
  • RNAP type III or C is responsible for the production of tRNA; it is moderately sensitive to amanitin
  • The  sigma  (σ) subunit  of prokaryotic  RNA polymerase Specifically recognizes the promoter site.
  • Alpha-amanitin inhibits RNA  polymerase  II of eukaryotes.
  • Rifampicin inhibits b-subunit of RNA  polymerase.
  • RNA polymerase (holoenzyme)= core enzyme+ sigma subunit
Don’t Forget to Solve all the previous Year Question asked on RNA Polymerase (RNAP)

Module Below Start Quiz

RNA Polymerase (RNAP)

RNA Polymerase (RNAP)

Q. 1 RNA polymerase recognizes? 
 A

Promoter site

 B Initiation site
 C Regulator site
 D Stop site
Q. 1 RNA polymerase recognizes? 
 A

Promoter site

 B Initiation site
 C Regulator site
 D Stop site
Ans. A

Explanation:

(40)        Promoter site REF: Harper 27`h ed p. 349

RNA polymerase has sigma sub unit which recognises promotor nucleotide sequence. It does not require primer and has no proof reading activity

Types:

  1. r RNA
  2. m RNA, mi RNA, Sn RNA
  3. t- RNA, 5s-rRNA, some SnRNA

Q. 2 To initiate transcription RNA polymerase does not require which one of the following:

 A

Template (ds DNA)

 B

Activated precursors (ATP, GTP, UTP, CTP)

 C

Divalent metal ions (Mn2+, Mg2+)

 D

Primer

Q. 2

To initiate transcription RNA polymerase does not require which one of the following:

 A

Template (ds DNA)

 B

Activated precursors (ATP, GTP, UTP, CTP)

 C

Divalent metal ions (Mn2+, Mg2+)

 D

Primer

Ans. D

Explanation:

DNA polymerase can only elongate existing polynucleotide chains, and thus requires a primer. RNA polymerase can initiate RNA synthesis de novo and hence does not require a primer.

Ref: Molecular Biology of the Gene Watson, 2004, Page 376 ;  Lippincott’s Illustrated Q & A Review of Biochemistry by Michael A. Lieberman, Rick Ricer, 2009, Page 294


Q. 3

The sigma (cr) subunit of prokaryotic RNA polymerase:

 A

Binds the antibiotic rifampicin

 B

Is inhibited by a-amanitin

 C

Specifically recognizes the promoter site

 D

Is part of the core enzyme

Q. 3

The sigma (cr) subunit of prokaryotic RNA polymerase:

 A

Binds the antibiotic rifampicin

 B

Is inhibited by a-amanitin

 C

Specifically recognizes the promoter site

 D

Is part of the core enzyme

Ans. C

Explanation:

C i.e. Specifically recognizes the promoter site

Quiz In Between


Q. 4

RNA polymerase does not require :

 A

Template (ds DNA)

 B

Activated precursors (ATP, GTP, UTP, CTP)

 C

Divalent metal ions (Mn2+, Mg2+)

 D

Primer

Q. 4

RNA polymerase does not require :

 A

Template (ds DNA)

 B

Activated precursors (ATP, GTP, UTP, CTP)

 C

Divalent metal ions (Mn2+, Mg2+)

 D

Primer

Ans. D

Explanation:

D i.e. Primer


Q. 5

The drug inhibiting DNA-dependent RNA polymerase in Mycobacteria is –

 A

INH

 B

Rifampicin

 C

Ciprofloxacin

 D

Ethionamide

Q. 5

The drug inhibiting DNA-dependent RNA polymerase in Mycobacteria is –

 A

INH

 B

Rifampicin

 C

Ciprofloxacin

 D

Ethionamide

Ans. B

Explanation:

Ans. is ‘b’ i.e., Rifampicin

Mechanism of action of important antitubercular drugs

o Rifampicin —> Inhibits DNA dependent RNA synthesis by inhibiting RNA polymerase.

o INH  —> Inhibits synthesis of mycolic acid which is a component of mycobacterial cell wall. o Pyrazinamide —> Inhibits synthesis of mycolic acid.

o Streptomycin —> Inhibits protein synthesis (translation).

o Ethambutol —> Inhibits incorporation ofmycolic acid into bacterial cell wall by inhibiting arbinosyltransferase.


Q. 6

RNA polymerase has which activity

 A

Primase

 B

Helicase

 C

Ligase

 D

Topoisomerase

Q. 6

RNA polymerase has which activity

 A

Primase

 B

Helicase

 C

Ligase

 D

Topoisomerase

Ans. A

Explanation:

 

DNA synthesis cannot commence with deoxyribonucleotides because DNA polymerase cannot add a mononucleotide to another mononucleotide.

  • Thus, DNA polymerase cannot initiate synthesis of complementary DNA synthesis strand of DNA on a totally single stranded template.
  • For this, they require RNA primer, which is a short piece of RNA formed by enzyme primase (RNA polymerase) using DNA as a template.
  • RNA primer is then extended by addition of deoxyribonucleotides.
  • Later on, the ribonucleotides of the primer are replaced by deoxyribonucleotides.
  • Primase is actually a DNA primase which has RNA polymerase activity. This DNA primase is also called DNA polymerase.

Quiz In Between



Post Transcriptional Modification Of Rna

POST TRANSCRIPTIONAL MODIFICATION OF RNA


  • The primary transcripts of both prokaryotic and eukaryotic tRNA and rRNA are post-transcriptionally modified by cleavage of the original transcripts by ribonucleases.
  • In Prokaryotes mRNA are is not subjected to post-transcriptional processing.
  • In eukaryotes, The collection of all the primary transcripts synthesized in the nucleus by RNA polymerase II is known as heterogeneous nuclear RNA (hnRNA).
  • The primary transcripts are extensively modified in the nucleus after transcription.

These modifications usually include:

A) 5′ “Capping”: 

  • The first of the processing reactions for pre-mRNA, The cap is a 7-methylguanosine attached “backward” to the 5′-terminal end of the mRNA, forming an unusual 5’→5′ triphosphate linkage.
  • Methylation of this terminal guanine occurs in the cytosol and is catalyzed by guanine-7-methyltransferase.

B) Addition of a poly-A tail:

  • Poly A tail is added to the 3′ end of the hnRNA
  • Polyadenylate Polymerase is the enzyme
  • Takes place in the nucleus
  • Poly  (A)  tail  translates  into  Polylysine
  • Length of Poly-A tail is up to 200 Adenine bases
  • These tails help to stabilize the mRNA (by protecting from 3r-exonuclease), facilitate exit from the nucleus, and aid in translation.
  • Some rRNAs do not have a poly-A tail,  e.g. mRNAs of histones and some interferons.

C) Removal of introns  (splicing):-

  • Intron: an Intervening sequence that does not code for the amino acid
  • Introns  are  exised  by RNA splicing by Sn-RNAs/Snurp.
  • Exon: Amino acid coding sequence Molecular machinery that carries out splicing is called Spliceosome
  • The process by which introns are excised and exons are linked to form functional mRNA are called splicing, Thus mature mRNA does not contain introns.
  • snRNA  combines  with  proteins to  form  small  nuclear  ribonucleoprotein  particles  (snRNPs  or  snurps)
  • It  is the snRNA  component  of snurps  that  catalyzes  splicing
  • Snurps are U, U4, Us and Uu. Defective splicing (splicing mutation) is the most common cause of β-thalassemia.
  • only about 1.5% of human DNA has coding sequence (exons), remaining is non-coding(introns).
  • Two important gene-silencing RNAs are :- (i) Micro RNAs, and (ii) interfering RNAs (siRNAs).

D) Alternate splicing :-

  • The hn-RNA molecules from some genes can be spliced in alternative way in different tissues.
  • Thus two or more different mRNA (and therefore 2 or more proteins) can be synthesized from same hnRNA.

Exam Important

  • Poly  (A)  tail  translates  into  Polylysine
  • Length of Poly-A tail is up to 200 Adenine bases
  • These tails help to stabilize the mRNA (by protecting from 3r-exonuclease), facilitate exit from the nucleus, and aid in translation.
  • Introns  are  exised  by RNA splicing by Sn-RNAs/Snurp.
  • Exon: Amino acid coding sequence Molecular machinery that carries out splicing is called Spliceosome
  • The process by which introns are excised and exons are linked to form functional mRNA are called splicing, Thus mature mRNA does not contain introns.
  • snRNA  combines  with  proteins to  form  small  nuclear  ribonucleoprotein  particles  (snRNPs  or  snurps)
  • It  is the snRNA  component  of snurps  that  catalyzes  splicing
  • Snurps are U, U4, Us and Uu. Defective splicing (splicing mutation) is the most common cause of β-thalassemia.
  • only about 1.5% of human DNA has coding sequence (exons), remaining is non-coding(introns).
  • Two important gene-silencing RNAs are :- (i) Micro RNAs, and (ii) Small interfering RNAs (siRNAs
Don’t Forget to Solve all the previous Year Question asked on POST TRANSCRIPTIONAL MODIFICATION OF RNA

Module Below Start Quiz

Post Transcriptional Modification Of Rna

POST TRANSCRIPTIONAL MODIFICATION OF RNA

Q. 1 Which of the following type of RNA has the splicing activity as a function?

 A

mRNA

 B

snRNA

 C

tRNA

 D

rRNA

Q. 1

Which of the following type of RNA has the splicing activity as a function?

 A

mRNA

 B

snRNA

 C

tRNA

 D

rRNA

Ans. B

Explanation:

Small Nuclear RNAs (snRNAs), a subset of the small RNAs, are significantly involved in rRNA and mRNA processing and gene regulation. Of the several snRNAs, U1, U2, U4, U5, and U6 are involved in intron removal and the processing of mRNA precursors into mRNA

 
Ref: Weil P. (2011). Chapter 34. Nucleic Acid Structure & Function. 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. 2

A segment of an eucaryotic gene that is not represented in the mature mRNA, is known as:

 A

Exon

 B

Intron

 C

Plasmid

 D

TATA box

Q. 2

A segment of an eucaryotic gene that is not represented in the mature mRNA, is known as:

 A

Exon

 B

Intron

 C

Plasmid

 D

TATA box

Ans. B

Explanation:

Introns are the RNA sequences in the primary transcript that are not found in the mRNA. Exons RNA sequences in the primary transcript that are found in the mRNA. A TATA box is a DNA sequence that indicates the point at which a genetic sequence can be read and decoded.
 
Transcription: Transcription is the process by which DNA is copied (transcribed) to mRNA, which carries the information needed for protein synthesis. Transcription takes place in two broad steps. First, pre-messenger RNA is formed, with the involvement of RNA polymerase enzymes. Second formation of Messenger RNA.
 
Transcription unit: is a linear sequence of DNA that extends from a transcription start site to a transcription stop site. The transcription unit—that portion of a gene that is copied by RNA polymerase—consists of coding regions of DNA (exons) interrupted by intervening sequences of noncoding DNA (introns). After transcription, during RNA processing, introns are removed and the exons are ligated together to form the mature mRNA that appears in the cytoplasm.
 
1) Transcription Steps: There are three main steps to the process of DNA transcription.
  • Initiation: RNA Polymerase Binds to DNA. DNA is transcribed by an enzyme called RNA polymerase. Specific nucleotide sequences tell RNA polymerase where to begin and where to end. RNA polymerase attaches to the DNA at a specific area called the promoter region.
  • Elongation: Certain proteins called transcription factors unwind the DNA strand and allow RNA polymerase to transcribe only a single strand of DNA into a single stranded RNA polymer called messenger RNA (mRNA). The strand that serves as the template is called the antisense strand. The strand that is not transcribed is called the sense strand.
  • Termination: RNA polymerase moves along the DNA until it reaches a terminator sequence. At that point, RNA polymerase releases the mRNA polymer and detaches from the DNA.
2) Pre mRNA processing:
  • RNA splicing: pre-mRNAs typically include introns.Exons:are the continuous coding regions. Introns: are the  noncoding intervening sequences. They may serve to separate functional domains (exons) of coding information in a form that permits genetic rearrangement by recombination to occur more rapidly than if all coding regions for a given genetic function were contiguous. Introns are removed by RNA processing in which the intron is looped out and cut away from the exons by snRNPs, and the exons are spliced together to produce the translatable mRNA.
Ref: Harper’s illustrated biochemistry, 26th Edition Page  319

 


Q. 3

Poly(A) tail translates into (i.e. on translation give rise to):

 A

Polyproline

 B

Polylysine

 C

Polyalanine

 D

Polyglycine

Q. 3

Poly(A) tail translates into (i.e. on translation give rise to):

 A

Polyproline

 B

Polylysine

 C

Polyalanine

 D

Polyglycine

Ans. B

Explanation:

B i.e. Polylysine

Codon

AAA

GGG

CCC

TTT/ UUU

Translation product

LysinQ

Glycine

Proline

Phenylalanine

Quiz In Between


Q. 4 Introns are exised by

 A

RNA splicing

 B

RNA editing

 C

Restriction endonuclease

 D

DNAase

Q. 4

Introns are exised by

 A

RNA splicing

 B

RNA editing

 C

Restriction endonuclease

 D

DNAase

Ans. A

Explanation:

A i.e. RNA splicing


Q. 5

A segment of a eukaryotic gene that is not represented in the mature messenger RNA is known as:

 A

Intron

 B

Exon

 C

Plasmid

 D

TATA box

Q. 5

A segment of a eukaryotic gene that is not represented in the mature messenger RNA is known as:

 A

Intron

 B

Exon

 C

Plasmid

 D

TATA box

Ans. A

Explanation:

A i.e. Intron


Q. 6

Splicing Activity is a function of:

 A

mRNA

 B

sn RNA

 C

r RNA

 D

t RNA

Q. 6

Splicing Activity is a function of:

 A

mRNA

 B

sn RNA

 C

r RNA

 D

t RNA

Ans. B

Explanation:

B i.e. snRNA

–   Self splicing introns function as ribozyme and do not require external protein enzymes or high energy cofactors (eg ATP). Intron forms lariat in group II but not in group I self splicing introns.

–  Splicing is process of removing introns (i.e. the segment of gene that is not represented in mature m-RNA) from primary transcript and joining (or ligating together) exons (RNA sequences that code protein)Q. It is mediated by sn RNP or snrups formed from sn RNAQ.

Small nuclear RNAs (sn RNAs) are involved in RNA splicingQ; small nucleolar RNAs (sno RNAs) are involved in r RNA modificationsQ; micro RNAs (mi RNAs) & small temporal RNAs (st RNAs) are involved in inhibition (regulation) of gene expression (gene silencing)Q; small interfering RNAs (si RNAs) are involved in RNA interference (RNAi)Q; and B2 RNA binds to pol II and block transcription of many genes during heat shock

– Mammalian genomes seem to encode more non coding RNAs (nc RNAs) than coding m RNAs. nC RNAs are RNAS that do not encode proteins including r RNAS, t RNAs, mi RNAs, si RNAs, st RNAs and sn RNAs.

Quiz In Between


Q. 7 Defect in Snurps causes ‑

 A

Defect in 5′ – capping

 B

Defect in addition of poly-A tail

 C

Defect in Splicing

 D

Defect in terminal addition of nucleotide

Q. 7

Defect in Snurps causes ‑

 A

Defect in 5′ – capping

 B

Defect in addition of poly-A tail

 C

Defect in Splicing

 D

Defect in terminal addition of nucleotide

Ans. C

Explanation:

 

m-RNA processing

Prokaryotic mRNA is functional immediately upon synthesis, i.e. prokaryotic primary transcript of mRNA is functional. Thus it does not require post-transcriptional modification. In Eukaryotes the primary tran­script of mRNA is the hn RNA (hetrogeneous nuclear RNA). After transcription hnRNA is extensively modi­fied to form functional mRNA. These modifications are as follows.

1) The 5′-capping :- This is the first processing reaction. 51-end of mRNA is capped with 7-methylguansosine. This cap helps in initiation of translation (protein synthesis) and stabilizes the structure of mRNA by protecting from 5′-exonuclease.

2) Addition of poly ‘A’ tail :- As the name suggests, multiple ‘A’ (adenylate) residues are added at 3’end.This poly-A tail is not transcribed from DNA, but rather added after transcription. These tails helps to stabilize the mRNA (by protecting from 3′-exonuclease), facilitate exit from the nucleus, and aid in translation. After mRNA enters the cytosol, the poly-A tail is gradually shortened. Some mRNAs do not have poly-A tail, e.g. mRNAs of histones and some interferons.

3) Removal of introns (splicing) :- Eukaryotic genes contain some coding sequences which code for protein and some intervening non-coding sequences which do not code for protein. The coding sequences are called `exons’ and intervening non-coding sequences are called `introns’. The process by which introns are excised and exons are linked to form functional mRNA is called splicing. Thus mature mRNA does not contain introns.

  • Splicesome Splicesome is an assembly made up of small nuclear RNA (snRNA), some proteins and hnRNA. snRNA combines with proteins to form small nuclear ribnonucleoprotein particles (snRNPs or snurps) that mediate splicing. It is snRNA component of snurps that catalyzes splicing. Snurps are U4, U5 and U6.
  • Only about 1-5% of human DNA has coding sequence (exons). Remaining is non-coding (introns).

4) Alternate splicing :- The hn-RNA molecules from some genes can be spliced in alternative way in different tissues. Thus two or more different mRNA (and therefore 2 or more proteins) can be synthesized from same hnRNA. For example, difference isoforms of tropomyosin in different tissues in due to alternate splicing.


Q. 8 Defect in Snurps causes‑

 A

Sickle cell anemia

 B

Thalassemia

 C

Marfan syndrome

 D

EDS

Q. 8

Defect in Snurps causes‑

 A

Sickle cell anemia

 B

Thalassemia

 C

Marfan syndrome

 D

EDS

Ans. B

Explanation:

 

Defective splicing (defect in snurps) is the most common mutation causing thalassemia.

  • Molecular defect in pathogensis of thalassemia:‑

A) β-Thalassemia

  • Most common type of genetic abnormality in β-thalassemia is point mutation i.e., nonsense.
  • Some may also occur due to deletion or insertion i.e., frame shift mutations.
  • Defect may occur at different steps of β-chain synthesis:

i) Splicing mutations

  • Mutations leading to aberrant splicing are the most common cause of P-thalassemia.

ii) Chain terminator mutations

  • This cause premature termination of mRNA translation.

iii) Promoter region mutations

  • This results in transcription defect.

B) α-Thalassemia

  • The most common cause of reduced a-chain synthesis is deletion of a-globin genes.
  • Rarely nonsense mutation may also cause a-thalassemia.

Q. 9 Splicing is a process of ‑

 A

Activation of protein

 B

Removal of introns

 C

Synthesis of protein

 D

Replication of DNA

Q. 9

Splicing is a process of ‑

 A

Activation of protein

 B

Removal of introns

 C

Synthesis of protein

 D

Replication of DNA

Ans. B

Explanation:

 
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined.

This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation.

For many eukaryotic introns, splicing is done in a series of reactions which are catalyzed by the spliceosome a complex of small nuclear ribonucleoproteins (snRNAs), but there are also self-splicing introns.

Quiz In Between



Disorders of heme biosynthesis

Disorders of heme biosynthesis


Disorders  of heme  biosynthesis

  • porphyrias are a group of inborn errors  (or occasionally acquired) defects of heme biosynthesis.
  • This results in in the accumulation and increased excre-tion of porphyrins or porphyrin precursors.
  • The mutations that cause the porphyrias are heterogenous.
  • Each porphyria results in the accumulation of a unique pattern of intermediates caused by the deficiency of an enzyme in the heme synthetic pathway.
  • “Porphyria” refers to the purple color caused by pigment-like porphyrins in the urine of some patients with defects in heme synthesis.

Clinical manifestations:

  • The porphyrias are classified as erythropoietic or hepatic, depending on the enzyme deficiency in bone marrow or in the liver.
  • Most of the porphyrias are inherited autosomal dominant `EXCEPT
  1. ALAD enzyme Deficiency [ADP]
  2. Gongenital Erythropoeitic Porphyria [CEp]
  3. Erythropoetic Protoporphyria [EPP]
  4. X Linked Protoporphyria [XLp]
  • Accumulation of ALA and PBG causes Neuropsychiatric  and accumulation of porphyrin causes Photosensitivity.

Erythropoietic porphyrias

  • usually present with cutaneous photosensitivity. Most common Porphyria in children is Erythropoietic protoporphyria (Epp).
  • This disease is caused by to a deficiency in ferrochelatase. Protoporphyrin accumulates in erythrocytes, bone marrow, and plasma.•Patients are photosensitive.

PORPHYRIA CUTANEA TARDA:

  • This disease is caused by a deficiency in uroporphyrinogen decarboxylase. Uroporphyrin accumulates in the urine.
  • It is the most common porphyria. Patients are photosensitive.
  • Uroporphyrinogen-I synthase (also called PBG dearninase or HMB synthase) causes Acute intermittent Porphyria
  • Uroporphyrtnogen  III  Synthase causes Congenital  erythropoietic.
  • Ferrochelatase (Heme synthase) causes Protoporphyria.

VARIEGATE PORPHYRIA

  • An acute disease caused by a deficiency in protoporphyrinogen oxidase.
  • Protoporphyrinogen IX and other intermediates prior to the block accumulate in the urine.
  • Patients are photosensitive.

HEREDITARY COPROPORPHYRIA:

  • An acute disease caused by a deficiency in coproporphyrinogen oxidase.Coproporphyrinogen III and other intermediates prior to the block accumulate in the urine.
  • Patients are photosensitive.

ACUTE INTERMITTENT PORPHYRIA:

  • An acute disease caused by a deficiency in hydroxymethylbilane synthase1.Porphobilinogen and δ-amino-levulinic acid accumulate in the urine.
  • Urine darkens on exposure to light and air. Patients are NOT photosensitive.
  • Porphyrias leading to accumulation of ALA and porphobilinogen, such as acute intermittent por phyria, cause abdominal pain and neuro psychiatric disturbances.
  • In the liver, heme normally functions as a repressor of the gene for ALAS1. Therefore, the absence of this end product results in an increase in the synthesis of ALA synthase1(derepression).

Exam Important

Erythropoietic porphyrias

  • usually present with cutaneous photosensitivity. Most common Porphyria in children is Erythropoietic protoporphyria (Epp).
  • This disease is caused by to a deficiency in ferrochelatase. Protoporphyrin accumulates in erythrocytes, bone marrow, and plasma.•Patients are photosensitive.

PORPHYRIA CUTANEA TARDA:

  • This disease is caused by a deficiency in uroporphyrinogen decarboxylase. Uroporphyrin accumulates in the urine.common porphyria. Patients are photosensitive.
  • Uroporphyrinogen-I synthase (also called PBG dearninase or HMB synthase) causes Acute intermittent Porphyria
  • Uroporphyrtnogen  III  Synthase causes Congenital  erythropoietic.
  • Ferrochelatase (Heme synthase) causes Protoporphyria.

VARIEGATE PORPHYRIA:

  • An acute disease caused by a deficiency in protoporphyrinogen oxidase.Protoporphyrinogen IX and other intermediates prior to the block accumulate in the urine.Patients are photosensitive.

ACUTE INTERMITTENT PORPHYRIA:

  • An acute disease caused by a deficiency in hydroxymethylbilane synthase1.Porphobilinogen and δ-amino-levulinic acid accumulate in the urine. Urine darkens on exposure to light and air. Patients are NOT photosensitive. 

 

Don’t Forget to Solve all the previous Year Question asked on Disorders of heme biosynthesis

Module Below Start Quiz

Disorders of heme biosynthesis

Disorders of heme biosynthesis

Q. 1 A girl on sulphonamides developed abdominal pain and presented to emergency with seizure. What is the probable diagnosis?

 A

Acute intermittent porphyria

 B

Congenital erythropoietic porphyria

 C

Infectious mononucleosis

 D

Kawasaki disease

Q. 1

A girl on sulphonamides developed abdominal pain and presented to emergency with seizure. What is the probable diagnosis?

 A

Acute intermittent porphyria

 B

Congenital erythropoietic porphyria

 C

Infectious mononucleosis

 D

Kawasaki disease

Ans. A

Explanation:

Abdominal pain is the most common symptom in Acute intermittent porphyria and is usually steady and poorly localized but may be cramping. Seizures can be due to neurologic effects or to hyponatremia.
Treatment of seizures is difficult because most anti seizure drugs can exacerbate AIP (clonazepam may be safer than phenytoin or barbiturates).
 
The drugs which precipitate attacks of acute intermittent porphyria are microsomal enzyme inducers.
They are metabolized by p450 enzyme. In response to these drugs the synthesis of cytochrome p450 proteins increases, leading to an enhanced consumption of heme, a component of p450 proteins.
This in turn causes a decrease in the concentration of heme in the liver.
Since the patient is deficient in enzymes synthesizing porphyrins it cannot makeup for the increase in demand of porphyrins.
This leads to increased accumulation of porphyrin precursors precipitating attacks of porphyria.
 
Some important drugs causing acute intermittent porphyria :-
  • Barbiturate
  • Chloramphenicol
  • Sulfonamides
  • Thiopental Na
  • Oral contraceptives
  • Phenylbutazone
  • Rifampicin
 
Ref: Desnick R.J., Balwani M. (2012). Chapter 358. The Porphyrias. 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. 2

A 27-year-old woman goes to an emergency room with severe abdominal pain. She had previously experienced similar episodes of pain that lasted several hours to a few days, but this episode is the most severe. She has also been experiencing nausea, vomiting, and constipation. The physician is left with the impression that she is agitated and somewhat confused, and an accurate history is difficult to elucidate. The patient is sent for emergency laparotomy, but no pathology is noted at surgery. Following the unrevealing surgery, an older surgeon comments that he had once seen a similar case that was actually due to porphyria.The porphyrias are biochemical abnormalities in which of the following pathways?

 A

Glycogen degradation

 B

Heme synthesis

 C

Lipoprotein degradation

 D

Nucleotide degradation

Q. 2

A 27-year-old woman goes to an emergency room with severe abdominal pain. She had previously experienced similar episodes of pain that lasted several hours to a few days, but this episode is the most severe. She has also been experiencing nausea, vomiting, and constipation. The physician is left with the impression that she is agitated and somewhat confused, and an accurate history is difficult to elucidate. The patient is sent for emergency laparotomy, but no pathology is noted at surgery. Following the unrevealing surgery, an older surgeon comments that he had once seen a similar case that was actually due to porphyria.The porphyrias are biochemical abnormalities in which of the following pathways?

 A

Glycogen degradation

 B

Heme synthesis

 C

Lipoprotein degradation

 D

Nucleotide degradation

Ans. B

Explanation:

The porphyrias are a group of rare, related diseases that have in common a block in the heme synthesis pathway. The block is usually partial rather than complete, and thus many of these patients have only intermittent symptoms. Most cases of porphyria present with either a neurovisceral pattern (including both psychiatric symptoms and abdominal pain) or with photosensitive skin lesions. These two patterns are associated with different forms of porphyria.
Must know:

  • Associate abnormalities of glycogen degradation (with the glycogen storage diseases, such as Von Gierke disease, Pompe disease, and Forbes disease.
  • Associate abnormalities of lipoprotein degradation with some forms of hyperlipoproteinemia (notably Type I).
  • Associate abnormalities of nucleotide degradation with Gout and Lesch-Nyhan syndrome.
Ref: Murray R.K. (2011). Chapter 31. Porphyrins & Bile Pigments. 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 The enzyme deficient in erythropoietic porphyria is:

 A

PBG deaminase

 B

Uroporphyrin II cosynthetase

 C

Coprophyrin

 D

Ferrochelatase

Q. 3

The enzyme deficient in erythropoietic porphyria is:

 A

PBG deaminase

 B

Uroporphyrin II cosynthetase

 C

Coprophyrin

 D

Ferrochelatase

Ans. D

Explanation:

 

–  Erythropoietic protoporphyria is due to deficiency of enzyme ferrochelataseQ.

–  All porphyrias are autosomal dominant (AD) except congenital erythropoietic porphyria (autosomal recessive, AR), ALA dehydratase (porphobilinogen) deficiency (AR) and X-linked protoporphyria (X-linked).

Quiz In Between


Q. 4 Which of the following porphyrias is not inherited as an Autosomal Dominant disorder-

 A

Acute Intermittent Porphyria

 B

Congenital Erythropoietic Porphyria

 C

Porphyria Cutanea Tarda

 D

Hereditary Coproporphyria

Q. 4

Which of the following porphyrias is not inherited as an Autosomal Dominant disorder-

 A

Acute Intermittent Porphyria

 B

Congenital Erythropoietic Porphyria

 C

Porphyria Cutanea Tarda

 D

Hereditary Coproporphyria

Ans. B

Explanation:

Ans. is ‘b’ i.e., Congenital erythropoietic porphyria

Inheritance of Porphyrias

Autosomal dominant                                       Autosomal Recessive                                   X-linked

o Acute intermittent porphyria (AIP)            o ALA dehydratase deficiency                   o X-linked protoporphyria

o Porphyria cutanea Tarda (PCT)                 o Congenital erythropoietic porphyria

o Hereditary coproporphyria (HCP)             o Erythropoietic protoporphyria o Variegate porphyria (VP)


Q. 5 In porphyrias, which of the following enzyme defects does not lead to photosensitivity

 A

Uroporphyrinogen synthase

 B

Uroporphyrinogen decarboxylase

 C

Protoporphyrinogen oxidase

 D

Coproporphyrinogen oxidase

Q. 5

In porphyrias, which of the following enzyme defects does not lead to photosensitivity

 A

Uroporphyrinogen synthase

 B

Uroporphyrinogen decarboxylase

 C

Protoporphyrinogen oxidase

 D

Coproporphyrinogen oxidase

Ans. A

Explanation:

Ans.a. Uroporphyrinogen synthase
(Ref Harper 29/e p3l2-314, 27/e p277)
In porphyrias, uroporphyrinogen synthase enqlme defects lead to Acute Intemittent Porphyria, which shows purely
ne urological manifestation witho ut photosensitivity.


Q. 6

Skin is not involved in ‑

 A

Erythropoietic porphyria

 B

Porphyria cutanea torda

 C

Acute intermittent porphyria

 D

Hereditary coproporphyria

Q. 6

Skin is not involved in ‑

 A

Erythropoietic porphyria

 B

Porphyria cutanea torda

 C

Acute intermittent porphyria

 D

Hereditary coproporphyria

Ans. C

Explanation:

Ans. is ‘c’ i.e., Acute intermittent porphyria

Type of Porphyria  Neuropsychiatric symptoms Skin symptoms/Phototoxicity 

Hepatic porphyrias

Acute intermittent porphyri a

5-ALA dehydratase deficiency

Hereditary coproporphyria

Variegate porphyria

Porphyria cutanea tarda

 
+
+
+
+
_
 
_
 _
+
+
+
 
 Erythropoietic porphyrias

Erythropoietic protoporphyria

Congenital erythropoietic porphyria

X-linked sideroblastic anemia

 
 _
_
_
 
+
+
_

Quiz In Between



Xenobiotics

xenobiotics


  • A xenobiotic is a compound that is foreign to the body
  • may be accidentally ingested or taken as drugs or compounds produced in the body by bacterial metabolism (Greek, xenos = strange).
  • They are  metabolized,  a process called  biotransformation(detoxification).
  • Metabolism  of  xenobiotics  in  two  phases (phase I and phase II).
  • The cytochrome P450 enzymes are involved in the biotransformation reactions, the most important  enzyme present on smooth endoplasmic reticullum.
  • They are heme containing enzymes, localized in the endoplasmic reticulum of liver.
  • so, Liver  is  the  major site  for  metabolism  of xenobiotics.
  • Cytochrome P450 contains phosphatidyl choline.
  • Phase one is the alteration of the foreign molecule, so as to add a functional group.
  • The products of metabolic transformations are either excreted directly or undergo further meta-bolism by phase two reactions.

Phase |  (non-synthetic)  reactions

1. Oxidative Reactions:

  • metabolism of compounds by oxidation (including hydroxylation), reduction, hydrolysis, cyclization and decyclization.
  • The oxidation and detoxification of alcohol is also an important function of the liver.
  • the alcohol dehydrogenase is an NAD linked enzyme, which is located in the cytosol. Aldehyde dehydrogenase is an NAD+dependent mitochondrial enzyme.

2. Reduction Reactions: 

  • compounds which are reduced and detoxified by the liver are nitro compounds, These are reduced to their amines, while aldehydes or ketones are reduced to alcohols.

3. Hydrolysis:

  • addition of water splits the toxicant into two fragments or smaller molecules., 
  • Esters, amines,hydrazines, amides, glycosidic bonds and carba-mates are generally biotransformed by hydrolysis.

PHASE TWO REACTIONS; CONJUGATIONS:

  • a new metabolite from phase 1  contains a reactive chemical group, e.g. hydroxyl (-OH),amino (-NH2), and carboxyl (-COOH).
  • Glucuronide conjugation is the most common Phase two reactions. Bilirubin is a good example for a compound conjugated and excreted as its glucuronide.
  • Formation of bilirubin diglucuronide is a normal metabolic reaction for detoxification of bilirubin by phase 2 reactions.
  • The glucuronic acid is added to xenobiotics by UDP-glucuronyl transferases, present in the endo-plasmic reticulum.
  • sulfation decreases the toxicity of xenobiotics, for eg Phenolic and alcoholic compounds are conju-gated with sulfate.(steroids and indole compounds.)
  • cysteine is derived from glutathione, which is the active conjugating agent,
  • For example, catechol-O-methyl transferase converts epinephrine to metanephrine. Pyridine is excreted as N-methyl pyridine.
  • Mercapto ethanol is excreted as 5-methyl mercapto ethanol.

Exam Important

  • metabolism of compounds by oxidation (including hydroxylation), reduction, hydrolysis, cyclization and decyclization.
  • The oxidation and detoxification of alcohol is also an important function of the liver.
  • Bilirubin is a good example for a compound conjugated and excreted as its glucuronide.
  • Formation of bilirubin diglucuronide is a normal metabolic reaction for detoxification of bilirubin by phase 2 reactions.
  • The glucuronic acid is added to xenobiotics by UDP-glucuronyl transferases, present in the endo-plasmic reticulum.
  • catechol-O-methyl transferase converts epinephrine to metanephrine. Pyridine is excreted as N-methyl pyridine.
Don’t Forget to Solve all the previous Year Question asked on xenobiotics

Module Below Start Quiz

Xenobiotics

xenobiotics

Q. 1 In metabolism of xenobiotics all of the following reactions occur in phase one except?

 A

Oxidation

 B

Reduction

 C

Conjugation

 D

Hydrolysis

Q. 1

In metabolism of xenobiotics all of the following reactions occur in phase one except?

 A

Oxidation

 B

Reduction

 C

Conjugation

 D

Hydrolysis

Ans. C

Explanation:

Conjugation[Ref. K.D.T. 7″/e p. 24, 25, 26]

  • Drugs are not intrinsic cellular constituents. They are xenobiotics.
  • They are eliminated from the body mainly through kidney.
  • Drug metabolism means necessary changes in the drug molecule which are essential .for easy excretion from the body.
  • Drug metabolism usually converts lipophilic chemical compounds into more readily excreted polar / water soluble / ionizable compounds.
  • When the drug turns polar it becomes more soluble in the extracellular fluid and thus more filterable in the renal tubules. The drug also becomes highly ionizable so it is less reabsorbale and hence readily excretable from the kidney.
  • The metabolism occcurs more or less in every tissue but mainly in the liver.

Usually the drug metabolism occurs in two phases –

  • Phase I and
  • Phase II
  • Phase I and phase II reactions are biotransformations of chemicals that occur during drug metabolism.

Phase I reactions

  • Phase I reactions usually preceede phase II reactions though not necessarily. During these reactions, polar molecules are either added or unmasked, which results in more polar metabolites of the original chemicals. These metabolites are more water solube than the original compound.
  • Phase I reactions can lead to either activation or inactivation of the drug.

Phase I reactions are usually of the following types :

  • Oxidation
  • Reduction
  • Hydrolysis
  • Cyclization
  • Decyclization
  • If the metabolites of phase I reactions are sufficiently polar they may be readily excreted at this point.
  • However many phase I products are not eliminated rapidly and undergo a subsequent reaction in which an endogenous substrate combines with the newly incorporated functional group to form a highly polar conjugate (Phase H reaction).

Phase II reactions

  • Phase H reactions are usually known as “conjugation reactions”.
  • This involves conjugation with glucuronic acid, sulfonates and glutathione.

The phase II reactions are ?

– Methylation          

– Acetylation

– Glucuronidation

  • The products of conjugation have increased molecular weight and are usually inactive unlike phase I reactions which often produce active metabolites.

Q. 2 All of the following enzymes and their reactions are involved in the metabolism of Xenobiotics, EXCEPT:

 A

Cytochrome oxidase

 B

Cytochrome p 450

 C

Methylation

 D

Hydroxylation

Q. 2

All of the following enzymes and their reactions are involved in the metabolism of Xenobiotics, EXCEPT:

 A

Cytochrome oxidase

 B

Cytochrome p 450

 C

Methylation

 D

Hydroxylation

Ans. A

Explanation:

Cytochrome oxidase is not mentioned as an enzyme in the metabolism of xenobiotics but Cytochrome P450 and Hydroxylation reactions are involved in Phase-1 metabolic reactions and Methylation forms a part of phase II reactions.

 
Ref: Harpers Biochemistry, 27th Edition, Page 633; Lippincott’s Illustrated Reviews: Pharmacology, 4th Edition, Page 14; Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th Edition, Page 44

Q. 3 In metabolism of xenobiotics all of the following reactions occur in phase one, EXCEPT:

 A

Oxidation

 B

Reduction

 C

Conjugation

 D

Hydrolysis

Q. 3

In metabolism of xenobiotics all of the following reactions occur in phase one, EXCEPT:

 A

Oxidation

 B

Reduction

 C

Conjugation

 D

Hydrolysis

Ans. C

Explanation:

Xenobiotic is a compound that is foreign to the body.
The principal classes of xenobiotics of medical relevance are drugs, chemical carcinogens, and various compounds that have found their way into our environment by one route or another, such as polychlorinated biphenyls (PCBs) and certain insecticides.

In phase 1, the major reaction involved is hydroxylation, catalyzed mainly by members of a class of enzymes referred to as monooxygenases or cytochrome P450s. Hydroxylation may terminate the action of a drug, though this is not always the case. In addition to hydroxylation, these enzymes catalyze a wide range of reactions, including those involving deamination, dehalogenation, desulfurization, epoxidation, pre oxygenation, and reduction. Reactions involving hydrolysis (eg, catalyzed by esterases) and certain other non-P450-catalyzed reactions also occur in phase 1.
 
In phase 2, the hydroxylated or other compounds produced in phase 1 are converted by specific enzymes to various polar metabolites by conjugation with glucuronic acid, sulfate, acetate, glutathione, or certain amino acids, or by methylation.
 
Conjugation reaction occurs in phase 2 and not in phase 1.
Ref: Murray R.K. (2011). Chapter 53. Metabolism of Xenobiotics. 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. 4 What is metabolised like xenobiotics

 A

Myoglobin

 B

Bilirubin

 C

Biliverdin

 D

Haemoglobin

Q. 4

What is metabolised like xenobiotics

 A

Myoglobin

 B

Bilirubin

 C

Biliverdin

 D

Haemoglobin

Ans. B

Explanation:

B i.e. Bilirubin


Q. 5

Bile salts undergo xenobiotics:

 A

After conjugation with taurine and glycine

 B

After conjugation with lysine

 C

After conjugation with betaglucuronic acid

 D

After conjugation with derived proteins

Q. 5

Bile salts undergo xenobiotics:

 A

After conjugation with taurine and glycine

 B

After conjugation with lysine

 C

After conjugation with betaglucuronic acid

 D

After conjugation with derived proteins

Ans. C

Explanation:

C i.e. Conjugation with betaglucuronic acid

– Phase I biotransformation reactions include Hydrolysis, Hydroxylation, Reduction, Oxidation, Oxidative Deamination, Dealkaylation and Epioxidation. Mn “High RODE”. Whereas phase II reactions include Glucronidation, Sulfation, Conjugation (with glucronic acid, glutathione, sulfate or aminoacids), Acetylation and Methylation. Mn “5G-SCAM”.

Cytochrome p450 monoxygenase is the main enzyme responsible for activation of xenobiotics (phase I hydroxylation reaction)Q.

Bilirubin is metabolized like xenobiotics; it is conjugated with beta glucronic acid in hepatocytes to convert a nonpolar hydrophobic bilirubin to a polar hydrophilic one which is readily excreted in bileQ.


Q. 6

In metabolism of xenobiotics all of the following reactions occur in phase one except?

 A

Oxidation

 B

Reduction

 C

Conjugation

 D

Hydrolysis

Q. 6

In metabolism of xenobiotics all of the following reactions occur in phase one except?

 A

Oxidation

 B

Reduction

 C

Conjugation

 D

Hydrolysis

Ans. C

Explanation:

Ans. is ‘c’ i.e., Conjugation


Q. 7

Xenobiotics are metabolized to ‑

 A

Increase water solubility

 B

Increase lipid solubility

 C

Make them nonpolar

 D

None of the above

Q. 7

Xenobiotics are metabolized to ‑

 A

Increase water solubility

 B

Increase lipid solubility

 C

Make them nonpolar

 D

None of the above

Ans. A

Explanation:

Ans. is ‘a’ i.e., Increase water solubility

BIOTRANSFORMATION (METABOLISM)

  • Most of the drugs are treated by the body as foreign substances (xenobiotics).
  • Like other foreign substances (xenobiotics), body tries to eliminate drugs by various mechanisms for ridding itself of chemical intruders.
  • Biotransformation means chemical alteration of the drug in the body.

Why drug transformation is necessary ?

  • Kidney plays a pivotal role in terminating the activity of drugs.
  • For renal excretion the drug tends to be polar (lipid insoluble/water soluble) so that it can not diffuse back from tubular lumen and can be excreted.
  • But pharmacologically active organic molecules (drugs) tend to be lipophlic (nonpolar) and remains unionized or only partially ionized at physiological pH.
  • Biotransformation is needed to render nonpolar (lipid soluble) compounds polar (water soluble) so that they are not reabsorbed in the renal tubules and are excreted.

Sites and processes of biotransformation

  • Primary site of drug metabolism is liver, others are – kidney, intestine, lung and plasma.

Biotransformation of drugs may lead to :-

LInactivation

  • Most drugs and their active metabolites are rendered inactive.

Active metabolite from an active drug

  • Many drugs are partially converted to one or more active metabolites.
  • The effects observed are the sumtotal of that due to the parent drug and its active metabolite.

Activation of inactive drugs

  • Few drugs are inactive as such and need conversion in the body to one or more active metabolites.
  • Such a drug is called prodrug.


RNA editing

RNA editing


RNA editing

  • RNA editing is a process through which the nucleotide sequence specified in the genomic template is modified to produce a different nucleotide sequence in the transcript.
  • Even after mRNA has been fully processed, it may undergo additional posttranscriptional modification in which a  base in the mRNA is altered. This is known as RNA editing.
  • There are two generic classes of RNA editing in nuclei, involving enzymatic deamination of either C-to-U or A-to-T nucleotides.
  • Current estimate suggest that 0.01% of mRNA is edited in this fashion
  • The best characterized example of C-to-U RNA editing is that of apolipoprotein B (apoB), which is mediated by a holoenzyme that contains a minimal core composed of an RNA-specific cytidine deaminase apobec-1, and its cofactor apobec-1 complementation factor (ACF).
  • (apo) B—an essential protein component of chylomi-crons and very low density lipoproteins (VLDL).
  • the C residue in the codon (CAA) for glutamine is deaminated to U, changing the sense codon to a nonsense or stop codon (UAA).
  • This results in a shorter protein (apo B-48, representing 48% of the message) being made in the intestine (and incorporated into chylomicrons) than is made in the liver (apo B-100, full-length, incorporated into VLDL)
  • the linear relationship between the coding sequence in DNA, the mRNA sequence, and the protein sequence is altered.
  • It is an exception to Central Dogma of molecular genetics.
  • The single apoB gene is transcribed into an mRNA that directs the synthesis of a 512kDa proteiry apo 8100 with 4536 amino acid residues.
  • A cytidine deaminase converts a CAA codon in the mRNA to UAA at a single specific site
  • Other examples of RNA editing o Glutamate Receptor (Glutamine changed toArginine) Trypanosome mitochondrial DNA.

Exam Important

  • Even after mRNA has been fully processed, it may undergo additional posttranscriptional modification in which a  base in the mRNA is altered. This is known as RNA editing.
  • There are two generic classes of RNA editing in nuclei, involving enzymatic deamination of either C-to-U or A-to-T nucleotides.
  • Current estimate suggest that 0.01% of mRNA is edited in this fashion
  • The best characterized example of C-to-U RNA editing is that of apolipoprotein B (apoB), which is mediated by a holoenzyme that contains a minimal core composed of an RNA-specific cytidine deaminase apobec-1, and its cofactor apobec-1 complementation factor (ACF)
  • It is an exception to Central Dogma of molecular genetics.
  • The single apoB gene is transcribed into an mRNA that directs the synthesis of a 512kDa proteiry apo 8100 with 4536 amino acid residues.
  • A cytidine deaminase converts a CAA codon in the mRNA to UAA at a single specific site
  • Other examples of RNA editing o Glutamate Receptor (Glutamine changed toArginine) Trypanosome mitochondrial DNA.
Don’t Forget to Solve all the previous Year Question asked on RNA editing

Module Below Start Quiz

RNA editing

RNA editing

Q. 1 Apoprotein A is found in :

 A

Chylomicrons

 B

VLDL

 C

HDL

 D

LDL

Q. 1

Apoprotein A is found in :

 A

Chylomicrons

 B

VLDL

 C

HDL

 D

LDL

Ans. C

Explanation:

C i.e. HDL


Q. 2

Apo B48 and apo 13,00 are expressed as two different apoproteins because of difference in :

 A

RNA editing

 B

RNA splicing

 C

Chromosomal loci

 D

Apo-B gene

Q. 2

Apo B48 and apo 13,00 are expressed as two different apoproteins because of difference in :

 A

RNA editing

 B

RNA splicing

 C

Chromosomal loci

 D

Apo-B gene

Ans. A

Explanation:

A i.e. RNA editing


Q. 3

APO B48 & APO B100 is synthesized from the same rnRNA; the difference between them is due to:

 A

RNA splicing

 B

Allelic exclusion

 C

 Deamination of cytidine to uridine

 D

Upstream repression

Q. 3

APO B48 & APO B100 is synthesized from the same rnRNA; the difference between them is due to:

 A

RNA splicing

 B

Allelic exclusion

 C

 Deamination of cytidine to uridine

 D

Upstream repression

Ans. C

Explanation:

C i.e. Deamination of cytidine to uridine IRef: Vasudevan

  • Least post translational modification occurs in prokaryotic mRNA, which is generally identical to its primary transcript. Post translational modification of t-RNA includes removal of introns from anticodon loop, trimming of 5′ & 3′ ends, methylation / reduction / deamination / alkylation / rearranging glycolsidic bond to produced modified bases like methylated bases, dihydrouracil (D) & pseudo uracil (W) bases in nucleus, whereas cleavage and attachment of CCA tailing occur in cytoplasmQ.
  • In RNA, gene during processing undergoes nucleoside modifications, nucleoside cleavage and terminal addition but not chemical hydrolysisQ.
  • Post translational modification of mRNA involves 5′ capping , 3′ polyadenylation (addition of poly ‘A’ tail at 3′ end), splicing (removal of non coding intervening or intron sequences and ligation / joining of coding exons) by Sn RNA/ Sn RNPs / Snurps or self splicing d/t ribozyme activity of self splicing introns with formation of lariat intermediates, RNA editing and secondary methylationQ.
  • Apo B-48 and Apo B-100 are synthesized from same Apo B gene and same ApoB- m-RNA. Apo B 100 is a 100 kDa protein synthesized in liver by full length translation of corresponding mRNA of Apo B gene. Apo – B-100 forms part of LDL, IDL and VLDL. Apo B-48 is a 48 KDa protein (48% shorter form of Apo B-100) synthesized in intestine by partial translation of same mRNA of Apo B gene. Apo B 48 forms part of chylomicron & chylomicron remnant. This difference between the sizes of Apo B100 and Apo B48 occurs because post transcriptional processing (editing) of Apo B mRNA , deaminates the cytidine (C) to uracil (U) in intestine at 2153 position. After cyti dine deamination the CAA codon (which codes glutamine in liver) becomes UAA (nonsense or stop codon) in intestine. This results in shorter apo B-48 protein being made in intestine (and incorporated into chylomicron) than is made in the liver full length Apo B-100, incorporated in to VLDL.

Quiz In Between



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