Comprehensive Report on Human Genome, SNPs, and Energy Metabolism

This report delves into the complexities of the human genome, starting with an overview of the Human Genome Project, highlighting the proportion of coding and non-coding sequences, and the significance of gene location using the BRCA2 gene as an example. It further discusses the implications of genome sequencing for disease diagnosis, genetic predispositions, gene therapy, and pharmacogenetics, with a focus on single nucleotide polymorphisms (SNPs) and their impact on drug metabolism. The report also addresses ethical considerations related to genetic testing and antenatal screening. Moving on to energy metabolism, it defines key terms like anabolism, catabolism, and the role of ATP, while elucidating the process of glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation within mitochondria. Finally, the report touches upon lipid metabolism, essential and non-essential fatty acids, prostaglandins, complex lipids, and various carrier proteins involved in cellular transport, ending with the application of FDG-PET imaging in cancer detection.

Running head: BIOCHEMISTRY
BIOCHEMISTRY
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The Human Genome Project involves the sequencing of all the DNA in a human cell.
All of the human cells which have a nucleus isolated from a particular individual, contains all
the information that is required to build up that particular individual. There are about 31,000
genes present in a human. The human genome is build-up of 3.2x 109 bases. Among them
only 1.1% of the proteins are involved in protein encoding. 28% of the genome is transcribed
to mRNA so only 5% of this is exons. The rest of the component is the introns which are
basically the meaningless sequences like the lysozyme enzyme gene that is 60kb but only
500b code the amino acid sequence. It is perceived that 50-60% single copy DNA sequences
includes most gene among which 25-40% are moderately repeated DNA. It is also seen that
10-15% simple sequence DNA (5-10bp) repeated in long arrays. During meiosis crossover
occurs in these regions.
The gene location on the chromosomes is shown by the BRCA2 gene which is the
breast cancer 2 early onset. It plays a role in DNA repair where the mutation increases risk of
breast, ovarian and prostate cancer. The cytogenic location is 13q12.3 where q=long arm of
chromosome - 12.3 – banding pattern and the Molecular Location on chromosome 13: base
pairs 32,314,861 to 32,399,849.
The significance of the genome sequencing shows an improved method of diagnosis
of the disease. This method allows the early detection of the genetic predispositions.
Additionally plays a role in gene therapy where the faulty genes can be replaced. This also
has a role in pharmacogenetics where the drug metabolism occurs by enzymes which vary
genetically between individuals. The drug blood concentration is too low for ineffective
treatment and is too high for the side effects.
Pharmacokinetics also involve single nucleotide polymorphism which is the most
common source of genetic variation, where there is replacement of the single nucleotide like

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for example C or T. SNP generally occurs between the genes however it can also occur in the
promotor or the structural part of the gene. The SNPs in genes that are coding for drug
metabolising enzymes can affect metabolism of specific drugs. Additionally could produce
different amount of enzyme or less efficient enzyme.
The BMA was able to identify a wide range situations where a disorder needs to be
tested. For the analysis of a specific gene, the product or the function or other DNA or
chromosome analysis, to detect or exclude an alteration likely to be associated with a genetic
disorder. This is of two types, where there is a predictive type and a diagnostic type. In the
predictive type there are no symptoms however in the diagnostic type there is a symptom of a
disorder.
The predictive tests involves the pre-symptomatic and pre-disposal tests like for
example Huntington ’s disease and BRCA 1 &2 increase risk of breast cancer respectively.
There are certain drawbacks like potential life insurance issues, lack of understanding of
genetics by layperson along with the family issues. There is also antenatal screening which is
carried out on all women.
The metabolic rate refers to the total energy produced and used by the body per unit
time. This metabolic energy is used for Basal metabolism, thermal effect of food-energy cost
of gut motility and digestive processes and for the muscular activity. The basic terms
associated with energy metabolism includes metabolism- : total of all the chemical changes
that occur in the body, anabolism that is combining of molecules to produce larger ones, e.g.
proteins, using energy and catabolism which is the breakdown of molecules into smaller ones
producing energy to drive energetically unfavourable reactions e.g. anabolism, ion transport
across membranes, muscle fibre contraction. ATP is basic currency of energy which is

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‘stored’ in the high energy bonds between the two terminal phosphate groups. This is
released/transferred when the terminal 1 or 2 phosphates binds to another molecule.
The cell energetics demonstrates the potential energy. This is the energy that is stored
in the high energy bonds that is the ATP. During oxidative phosphorylation or glycolysis
ADP condenses with a phosphate to produce ATP. ATP is the most important molecule for
capturing energy. Hydrolysis of the bond between the two end phosphates releases
7.3kcal/mol of energy.
The carbohydrates mainly comprises of the C, H and O. • C:H:O ratio 1:2:1 same as
C+H2O therefore hydrated Cs, where the O content is highly polar. There are different types
which consists of monosaccharides having smallest unit of a carbohydrate including aldoses
and ketoses. Glucose and fructose are the monosaccharides. The next are the disaccharides
where the monosaccharides are joined by a glycosidic linkage. Sucrose (‘sugar’) consists of
an α-D- glucose linked at C1 to C2 of β-Dfructose. Can be abbreviated to D-Glc-(α1→2)-D-
Fru. The next are the polysaccharides like glycogen and starch.
The following shows the process of glycolysis that helps in the breakdown of glucose.

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The Tricarboxylic acid cycle

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The mitochondria occupies 25% of cell cytoplasm. Outer membrane porous to small
molecules due to porons. Inner membrane 76% protein (e.g. transporters for ADP and ATP,
electron transport chain. In mitochondria, acetyl CoA generated from sugars, fatty acids or
from some amino acids enter the TCA cycle. Also electrons, obtained by glycolysis
(associated with H ions carried on NADH molecules) enter the mitochondria to be transferred
ultimately to O2 producing ATP.
Oxidative phosphorylation is the production of ATP from ADP and phosphate via
transfer of electrons. The electric transport chain are a series of carriers present on the interior
of the mitochondrial membrane.
The process of ATP production can be summarized as follows:

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 Glucose: 1 Glucose molecule produced: By glycolysis 2ATP molecules directly and 2
NADH+H+ (to be used to produce 6 units of ATP) By Pyruvate conversion to acetyl
CoA 2 NADH+H+ (to be used to produce 6 units of ATP) By conversion of acetyl
CoA to CO2 (TCA cycle) 6 NADH+H+ (to be used to produce 18 units of ATP),
2FADH2 (to be used to produce 4 units of ATP) and 2 GTPs. Total of 38 ATPs but 2
used to prepare glucose for ATP production so net 36 ATPs.
 Fats: Triglycerides in adipose broken down to glycerol and fatty acids (FA) in
response to hormones such as epinephrine. FAs transported to cell and in the
mitochondria the acyl chains (chains of C-H) are degraded 2C units at a time and
converted to acetyl CoA to enter TCA.
Lipids are a heterogeneous group of compounds including the fats, phospholipids,
steroids & prostaglandins. Some of the functions of lipids include storage of energy,
protection and insulation and others. The fatty acids are formed by the sequential addition
of 2C (acetate) units. There are certain essential and non-essential fatty acids. For the
breakdown of fatty acids, the most common method is β-oxidation.
The prostaglandins are a large family of molecules that are derived from fatty acids.
The regulatory effects include muscle contractor, Vasoconstrictor and dilator and others.
There are several classes of complex lipids which are as follows:
I.Lipids containing glycerol • Neutral fats • Phosphoglycerides • II. Lipids not containing
glycerol • Sphingolipids • Aliphatic alcohols and waxes • Steroids • III Lipids combined
with other compound classes • e.g. Lipoproteins.
Types of carrier proteins involve ATP-powered pump and the channel proteins and
the transporters. The ion gradient is able to cross the cell membrane and drive the

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biological processes. The secondary active transport is an active transport process having
antiporters.
The FDG-PET imaging of cancer helps to show that cancer slows the enhanced uptake
abd metabolism of glucose. Due to this cancers accumulate FDG at a greater rate than do
normal tissues.