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Biochemistry

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THE COMPLETE NEET PATTERN BOOK FOR BIOCHEMISTRY

Dr. Soumya Kurup (MD)

Jr, Govt. Medical College, Calicut

Rank #55 in DNB-CET, November 2013 &
Rank #165 in AIPGMEE 2014

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Topic-wise presentation of all chapters!

BIOCHEMISTRY

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NUCLEOTIDES

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CHAPTER 5

NU CL EO T IDE S

CHAPTER

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Contents

Introduction
Purine bases
n
Biosynthesis & Catabolism of Purine Nucleotides
n
Disorders of Purine Metabolism
Pyrimidine Bases
n
Biosynthesis & Catabolism of Pyrimidines
n
Regulation of nucleotide synthesis:
n
Disorders of pyrimidine metabolism
dna
n
Structure
n
Different types of dna
n
Denaturation of dna
rna
n
Chemical Nature
n
Types of rna
dna Organisation
n
Microsatellite repeat sequences
n
Trinucleotide repeat disorders
dna Replication
n
dna repair mechanisms
n
drugs Affecting Nucleic Acids
Rna Synthesis, Processing & Modification
n
Transcription
n
Posttranscriptional Processing
Genetic Code
Translation: Protein Synthesis
n
Intracellular traffic & sorting of proteins
n
Protein degradation
n
Posttranslational processing
n
Inhitors of Protein Synthesis
Regulaiton of Gene Expression
n
Gene Amplification
n
Gene Rearrangement
n
Transposition of DNA
n
Transcriptional Switch
Mitochondrial DNA
n
Disorders due to mutations in mitochondrial DNA

BIOCHEMISTRY

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Bullet points and Images for quicker learning!

VITAMINS

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CHAPTER 9

(petechiae, ecchymoses, perifollicular hemorrhages)

Inflamed and bleeding gums
Manifestations of bleeding into joints, the peritoneal cavity, the pericardium,
and the adrenal glands.
In children, vitamin C deficiency may cause impaired bone growth.
n
n

Radiological findings
Wimbergers ring sign: Circular, opaque radiologic shadow surrounding epiphyseal centers of ossification, which may result from bleeding
Frankels line: Dense zone of provisional calcification
Trummerfeld zone: Lucent metaphyseal band underlying Frankels line
Pelken spur: Metaphyseal spurs which result in cupping of the metaphysis
n

n
n

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Laboratory diagnosis of vitamin C deficiency is made on the basis of low plasma
or leukocyte levels.
Treatment g Administration of vitamin C (200 mg/d) improves the symptoms
of scurvy within days
n

Benefits from higher intakes of vitamin

n

High-dose vitamin C supplementation (e.g. 12 g/d) may slightly decrease the

symptoms and duration of upper respiratory tract infections.

Vitamin C supplementation has also been reported to be useful in ChdiakHigashi syndrome and osteogenesis imperfecta
Diets high in vitamin C have been claimed to lower the incidence of certain
cancers, particularly esophageal and gastric cancers
n

Toxicity
n
n

Taking >2 g in a single dose may result in abdominal pain, diarrhea, and nausea
Vitamin C may be metabolized to oxalate. So patients with a past history of

kidney stones not to take large doses of vitamin C.

Chronic high doses could promote iron overload in patients taking supplemental iron.
n

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BIOCHEMISTRY

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Question based facts provided with the content!

NUCLEOTIDES

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CHAPTER 5

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30 nm

single octamer.
Core particles are separated by a 30 base pair region of DNA termed linker giving
a bead-on-string appearance.

Octameric histone core

H1 histone

10 nm
DNA
H1 histone

DNA

Histone
octamer

Nucleosome

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30 nm

Four core histones are subject to atleast six types of covalent modifications
or posttranslational modifications which play an important role in chromatin
structure & function.

Possible roles of modified histones

Tumour suppressor gene

is deactivated by:
Histone deacetylation
Histone methylation (also
called hypomethylation)

Epigenetic anticancer
drugs act by inhibiting
covalent modification of
histones of tumour
suppressor gene:
Histone deacetylase
inhibitors g Vorinostat,
Romidepsin
Histone hypomethylation
inhibitors g Azacytidine

Decitabine

Zebularine
n

Acetylation of histones H3 & H4 is associated with activation or inactivation

ofgene transcription
Acetylation of core histones is associated with chromosomal assembly during
DNA replication
Phosphorylation of histone H1 is associated with the condensation of
chromosomes during replication
ADP-ribosylation of histones is associated with DNA repair
Methylation of histones is correlated with activation & repression of gene
transcription
Monoubiquitylation is associated with gene activation, repression &
heterochromatic gene silencing.
Sumoylation of histones (SUMO; small ubiquitin-related modifier) is
associated with transcription repression
Order of organisation of DNA into chromosomes
n

n
n

Naked
double
helical
DNA

beads on
string
10nm
chromatin
fibril

30nm
chromatin
fibril (with
nucleosomes
supercoiled)

Non condensed
loops or
domains
anchored in
scaffolding (the
nuclear matrix)

Loops
further
condensed
to form
chromosome

Concepts explained with examples.

BIOCHEMISTRY

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NUCLEOTIDES

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n Rate limiting process in

translation initiation is the
recognition of mRNA cap
structure by eIF-4E

CHAPTER 5

32

Complete 80S ribosome has three sites:

A site (aminoacyl site)

Carries the new incoming tRNA with the amino acid to be added
next to the polypeptide chain

P site (peptidyl site)

Carries the peptidyl tRNA with the growing peptide chain

E site (exit site)

Deacylated exit site tRNA at P site after transferring the growing

peptide chain to the newcomer amino acyl tRNA at A site exits
through this site

Elongation
Elongation is a cyclical process on the ribosome in which one amino acid at a
time is added to the nascent peptide chain.
Elongation involves several steps catalysed by proteins called Elongation factors
(EF)
n

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Steps
n

Binding of amino acyl tRNA to the A site:

Correct aminoacyl tRNA according tothe mRNA codon enters the A site
It requires Elongation factor 1A and hydrolysis of GTP.
Peptide bond formation:
-amino group of new aminoacyl tRNA in the A site reacts with carboxyl group
of the peptidyl tRNA at the Psite to form the peptide bond
Catalysed by Peptidyl transferase (a component of 28S RNA of 60s ribosomal
subunit; an example of ribozyme)
No further energy is required for peptide bond formation as the amino acid is
already activated at the time of aminoacyl-tRNA formation.
Peptide bond formation results in attachment of growing peptide chain from P
site tRNA to the tRNA at A site
Translocation:
Elongation factor 2 binds to and displaces the peptidyl tRNA from the A site to
the P site
Deacylated tRNA from the P site is in turn translocated to the E site, from
which it leaves the ribosome.
A site is now open for reception of next aminoacyl tRNA for another cycle of
elongation.
Translocation requires hydrolysis of one molecule of GTP.
It is easier to understand the process of translation, if you consider the ribosomal
assembly as a home. The new comer tRNA with amino acid, at A site is the bride. tRNA
at the peptidyl site carrying the growing peptide chain is the home-maker mother and
empty tRNA at E site is the grand mother. The new bride comes to the family with some
virtues (amino acid) that is added to the tradition of the family (growing peptide chain
by peptide bond formation). Now the mother eventually transfers the responsibility of the
family (growing peptide chain) to the daughter in law. Now the daughter-in-law moves
to the position of the home maker (P site) and the mother moves to the position of grand
mother. This process continues.
n

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Biochemistry cycles simplified!

BIOCHEMISTRY

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tca cycle

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CHAPTER 2

TCA CYCLE, ETC, STARVE-FEED

CYCLE, METABOLISM OF ALCOHOL

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DEFINITION

TCA CYCLE

(Also known as Krebs cycle/ Citric acid cycle is the final common pathway)
ATP

Acetyl CoA

Malate
dehydrogenase

Oxaloacetate

NADH

Malate

NAD

Citrate synthase

Fluroacetate

Citrate

Aconitase

Cis-Aconitate
Aconitase
Fumarase
nadh
Total 1QATP
D-Isocitrate
adP
per cycle
NAD
Isocitrate
dehydrogenase
NADH
Fumarate
Oxalosuccinate
FADH2
Isocitrate
CO2
Succinate
FAD
dehydrogenase
dehydrogenase
ATP
a-Ketoglutarate
Succinate
NADH NAD
ADP
Malonate
Succinyl
Isocitrate
CoA
Succinyl
a-ketoglutarator
thiokinase
dehydrogenase
CO2
Green g Enzymes
Violet g Coenzymes
Red g ATP
Black g Inhibitors

Arsenite

The sequence of reactions in mitochondria that g oxidises the acetyl moiety

of acetyl CoA and g reduces coenzymes that are reoxidised through the electron
transport chain, linked to the formation of ATP.
n TCA cycle is the final common pathway for the oxidation of carbohydrate, lipid,
and protein because g glucose, fatty acids and most amino acids are metabolised to
acetyl CoA or intermediates of the cycle

BIOCHEMISTRY

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Recent advances in biochemistry covered!

MOLECULAR GENETICS, RECOMBINANT DNA & GENOMIC TECHNOLOGY

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CHAPTER 8

- New light has been thrown on human evolution

- Procedures for tracking disease genes have been greatly refined
- It has given major contributions for the understanding of human health and
disease
- It has led pavement for researches on shortest and most efficient path to
curing diseases
- As an outgrowth of Human Genome Project, many so called-omics fields
have sprung up, involving comprehensive studies of the structures and functions of
the molecules with which each is concerned

Some Terminologies
Genomics

Study of entire genome of an organism. Genome is the set of all

genes expressed by the organism

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Proteomics

Quantitative and qualitative study of entire proteome. Proteome

is the set of all proteins expressed by a cell at a particular time.
It includes their relative abundance, distribution, posttranslational
modifications, functions and interactions with other macromolecules

Glycomics

Glycomics is the comprehensive study of glycomes (the entire

complement of sugars, whether free or present in more complex
molecules, of an organism), including genetic, physiologic,
pathologic, and other aspects

Pharmacogenomics

The study of genetically determined variations in responses to drugs

in human or in laboratory organisms

Transcriptomics

The study of transcriptome, which is the set of all RNA molecules,

including mRNA, rRNA, tRNA, and other non-coding RNA produced
in one or a population of cells.

Metabolomics

The study of the metabolome,which represents the collection of all

metabolites in a biological cell, tissue, organ or organism, which
are the end products of cellular processes. Thus, while mRNA gene
expression data and proteomic analyses do not tell the whole story
of what might be happening in a cell, metabolic profiling can give
an instantaneous snapshot of the physiology of that cell.

Chromosome
walking

Chromosome walking is amethod of sequencing DNA and involves

repeated cloning of overlapping DNA segments Primer walking is
a sequencing method of choice for sequencing DNA fragments
between 1.3 and 7 kilobases. The term primer walking is used
where the main aim is to sequence the genome. The term
chromosome walking is used instead when we know the
sequence but dont have a clone of a gene

Chromosome
jumping

Another method of DNA sequencing

In this DNA is cut into relatively larger fragments and circularised.
So one can move more quickly and cover greater lengths of DNA
than with chromosome walking [remember: jumping genes are
transposons, DNA sequence that can change its position within the
genome]

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BIOCHEMISTRY

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Related points from Pharmacology covered!

NUCLEOTIDES

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CHAPTER 5

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Drugs affecting nucleic acids

Mechanism

Drugs

Antibiotics
DNA gyrase inhibitors

Quinolones (nalidixic acid and

fluoroquinolones)
Novobiocin

RNA polymerase inhibitors (inhibits

transcription)

Rifampicin

Drugs destroying DNA

Metronidazole (generates reactive

nitro radicals in anaerobic conditions)
Nitrofurantoin

Nucleotide/nucleoside analogues

Idoxuridine
Acyclovir
NRTI (eg. zidovudine,lamivudine etc)

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Guanine content equal to cytosine;
adenine content equal to thymine

Anticancer drugs

Alkylation of nucleophilic groups on DNA

bases leading to cross-linking of bases,
abnormal base pairing, and DNA strand
breakage.
N7 of guanine is most susceptible for
alkylation
(Drug which is included in alkylating agents
group but primarily affectsRNA and protein
synthesis g Dacarbazine)

Purine analogues
Activated by HGPRTase Resulting nucleotide
inhibits enzymes in purine biosynthesis

6-mercaptopurine, 6-thioguanine
Fludarabine, Cladribine (adenine
analogues)

Pyrimidine analogues

Cytarabine, 5-flurouracil, capecitabine

(prodrug of 5-FU), gemcitabine,
5-azacytidine, decitabine

Topoisomerase I inhibitors

Camptothecins (topotecan, irinotecan)

Topoisomerase II inhibitors

Epipodophyllotoxins (etoposide,
teniposide)
Anthracycline antibiotics (doxorubicin,
daunorubicin)

Inhibiting DNA dependant RNA synthesis

Actinomycin-D (Dactinomycin)

Acts in G2 phase of cell cycle causing DNA

strand breakage and free radical formation

Bleomycin

Inhibits adenosine deaminase enzyme

Pentostatin

Inhibits ribonucleotide reductase (an

enzyme that catalyzes the formation of
deoxyribonucleotides from ribonucleotides in
DNA synthesis)
Induces the synthesis of fetal hemoglobin

Hydroxyurea

BIOCHEMISTRY

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Related points from Medicine (Harrison) covered!

MINERALS

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CHAPTER 10

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Diagnosis
Tests for Wilsons Disease
Test
Serum
ceruloplasmin
KF rings

24-h urine Cu

Usefulness
+
++

+++

Normal Value

Wilsons disease

180 - 350 mg/L

(18 - 35 mg/dL)

Low in 90%

Absent

Present in 99% + if neurologic or

psychiatric symptoms present.
Present in 30 - 50% in hepatic presentation and presymptomatic state

0.3 - 0.8 mmol

(20 - 50 mg)

>1.6 mmol (>100 mg) in symptomatic patients0.9 to >1.6 micromol

(60 to >100 microgram) in presymptomatic patients

Liver Cu

++++

>3.1 mmol (>200 mg) (obstructive

0.3 - 0.8
liver disease can cause false-positive
mmol/g
(20 - 50 mg per results)
g tissue)

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Haplotype
analysis

++++
(Siblings only)

0 Matches

2 Matches

Treatment

Recommended Anticopper Drugs for Wilsons Disease

Disease Status

First Choice

Second Choice

Initial hepatic
Hepatitis or cirrhosis without
decompensation

Zinc

Trientine

Hepatic decompensation
Mild
Moderate
Severe
Initial
Maintenance
Presymptomatic
Pediatric
Pregnant

Trientine and zinc

Trientine and zinc
Hepatic transplantation
Tetrathiomolybdate and zinc
Zinc
Zinc
Zinc
Zinc

Penicillamine and zinc

Hepatic transplantation
Trientine and zinc
Zinc
Trientine
Trientine
Trientine
Trientine

Some interesting points about Wilson disease:

The younger the patient, the more likely hepatic involvement will be the
predominant manifestation.
Girls are 3 times more likely than boys to present with acute hepatic failure.
After 20 years of age neurologic symptoms predominate
Kayser Fleischer ring may be absent in young patients with liver disease but are
always present in patients with neurologic symptoms
KF ring is not unique to Wilson disease but in Wilson, a complete KF ring is
seen
n

n
n
n

Nazer prognostic index is

used to establish disease
severity in Wilsons disease
presenting with hepatic
decompensation. The
laboratory parameters for
calculation are:
n
n

Serum bilirubin
Serum aspartate

transferase (AST)

Prolongation of
prothrombin time
n

NEET Pattern questions covered!

BIOCHEMISTRY

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proteins

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CHAPTER 11

neet pattern (nbe based) questions

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Cytosolic (free) ribosomes

n
n
n
n
n

Cytosolic proteins like Hb

Cytoskeletal proteins
Mitochondrial proteins
Nuclear proteins
Peroxisomal proteins

Bound (rough ER) ribosomes

n

n
n

All membrane proteins (mitochondrial,

ER, golgi, plasma membrane)
Secretory proteins
Lysosomal enzymes

Tyrosinemia typ I

Fumaryl acetoacetate hydroxylase

Tyrosinemia typ II

Tyrosine transaminase

Neonatal tyrosinemia

Hydroxyl phenyl pyruvate hydroxylase

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Preview

Biochemistry is an important subject for NEET pattern.

But we often tend to skip important topics or concepts

due to lack of time. Biochemistry Wave offers a solution to
this problem by breaking down the theory to points and
presenting in a manner that can be understood better, read
faster and more importantly can be revised towards the end.

It will be useful to all PG aspirants. Good luck!

Dr. Nimitha P
JR in Dermatology, AIIMS, New Delhi
Rank 33, AIPGMEE 2015
Rank 55, AIIMS November 2014

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