CYL456: Chemistry of Life – An Introduction
Biomolecules
Common metabolic pathways
Instructor: Yashveer Singh, PhD
General, Organic, and Biological Chemistry, HS Stoker,
Brooks/Cole
Timberlake’s Chemistry: An Introduction to General, Organic, and
Biological Chemistry, KC Timberlake, Prentice Hall
6 November 2014
Metabolism
Metabolism refers to all biochemical reactions taking place in
living organisms. An average human adult whose weight remains the
same for 40 years processes about 6 tons of solid food and 10,000
gallons of water
The simplest living cells also carry out energy intensive processes
like protein synthesis, DNA replication, RNA transcription, and
membrane transport
Catabolism refers to reaction in which large biochemical
molecules are broken down to smaller ones, usually with the release
of energy (e.g., glucose oxidation)
Anabolism refers to reaction in which small biochemical molecules
are joined together to form larger ones, usually with energy input
(e.g., protein synthesis from amino acids)
Metabolism = catabolism + anabolism
Metabolic reactions in cell usually use series of consecutive
biochemical reactions to convert a starting material into the product,
and hence the term metabolic pathways
Metabolic pathways could be linear or cyclic
Since major metabolic pathways of all life forms are similar, the
term “common metabolic pathways” is used to describe them
Common metabolic pathways
Metabolism and cell structure Most of the energy is
produced in cristae of
mitochondria, hence
the term power house of
cell for mitochondria
Intermediates in metabolic pathways – adenosine
triphosphate (ATP)
ATP is a nucleotide triphosphate and used to store and release
energy
Intermediates in metabolic pathways – adenosine
triphosphate (ATP)
ATP is hydrolyzed to ADP, releasing phosphate group and energy.
ADP can be further hydrolyzed to AMP, releasing another phosphate
group and energy
Phosphate-containing compounds
in metabolic pathways are high-
energy compounds
These compounds have greater
free energy of hydrolysis than other
compounds
Have one or more highly reactive
strained bonds. Energy required to
break strained bonds is
comparatively lower
Difference between the energy
needed to break bonds and that
released during the bond formation
is much higher
Intermediates in metabolic pathways – adenosine
triphosphate (ATP)
Intermediates in metabolic pathways – flavin adenine
dinucleotide (FAD)
FAD is a coenzyme required in metabolic redox reactions
Intermediates in metabolic pathways – flavin adenine
dinucleotide (FAD)
FAD is converted to
FADH2 by accepting
two hydrogen and
two electrons
(reduced). The
process is reversible
and used to generate
double bonds
Intermediates in metabolic pathways – nicotinamide
adenine dinucleotide (NAD+)
NAD+ is a coenzyme required in metabolic redox reactions. It
accepts one hydrogen and converted to NADH. An additional
hydrogen remains in the system and the process is reversible
Intermediates in metabolic pathways – nicotinamide
adenine dinucleotide (NAD+)
NAD+ is
employed to
oxidize
secondary
alcohol to
ketone
Coenzyme A transfers acetyl group in metabolic pathways
Intermediates in metabolic pathways – coenzyme A
(CoA-SH)
Coenzyme A has a free thiol group (-SH), which can be acetylated
(attachment of CH3CO- group) to form acetyl CoA. The acetyl CoA
can be hydrolyzed to release the acetyl group (CH3CO- ) and free
CoA with thiol group
Intermediates in metabolic pathways – coenzyme A
(CoA-SH)
Triacylglycerols (TAGs) are insoluble in water and water-based
salivary enzymes in the mouth have no effect on them
It undergoes a major physical change. The churning action of the
stomach breaks up triacylglycerol into small globules, or droplets,
which float as a layer above the other components of swallowed
food. This is called chyme
Along with chyme formation, about 10% of TAGs undergo
hydrolysis in the stomach due to the presence of enzyme gastric
lipase
Digestion and absorption of lipids
Arrival of chyme into small intestine triggers the release of bile
(emulsifier) stored in gall bladder through the action of the hormone
cholecystokinin
Bile emulsification action solubilizes the TAG globules and
digestion resumes with the help of enzymes pancreatic lipases,
which hydrolyze ester linkages between the glycerol and fatty acid
units of the TAGs. Complete hydrolysis does not usually occur; only
two of the three fatty acid units are liberated
Bile combines the free fatty acids and monoacylglycerols into
micelles
Digestion and absorption of lipids
Repackaging occurs within the
intestinal cells. The free fatty acids and
monoacyl glycerols are reassembled into
triacylglycerols and combined with
membrane lipids (phospholipids and
cholesterol) and water-soluble proteins to
produce a lipoprotein called a
chylomicron
A chylomicron transports
triacylglycerols- it enters the lymphatic
system through small lymphatic vessels
lining the intestine. It enters the
bloodstream through the thoracic duct (a
large lymphatic vessel just below the
collarbone), where the fluid of the
lymphatic system flows into a vein
Digestion and absorption of lipids
Digestion and absorption of lipids
In blood, TAGs are hydrolyzed to produce glycerol and free fatty
acids by lipoprotein lipases. The fatty acid and glycerol are absorbed
by the cells of the body and are either broken down to acetyl CoA for
energy or stored as lipids
TAG are stored in adipocyte, a TAG-storing cell
Adipose tissues are primarily located beneath the skin, particularly
in the abdominal region, and in areas around vital organs
Adipose cells are among the largest cells in the body and differ
from other cells in that most of the cytoplasm has been replaced
with a large TAG droplet
The hydrolysis and release of fatty acid and glycerol from TAG
in adipocytes is triggered by hormones, like epinephrine and
glucagon. Hormone interacts with membrane receptors and
stimulates production of cAMP using ATP present in adipose cells.
The cAMP activates hormone-sensitive lipase (HSL) through
phosphorylation. HSL hydrolyzes the TAG into fatty acid and
glycerol
The process of tapping the body’s TAG reserves, in adipose tissue,
for energy is called triacylglycerol mobilization
Digestion and absorption of lipids
Digestion and absorption of lipids
Proteins supply only 10% body’s energy need, and rest comes from
carbohydrates and fats
Protein metabolism
Proteins are denatured in the stomach by the hydrochloric acid
present in gastric juice (pH 1.5-2.0). The enzyme pepsin hydrolyzes
about 10% of peptide bonds in proteins, producing a variety of
polypeptides
Enzyme trypsin, chymotrypsin, and carboxypeptidase in
pancreatic juice further hydrolyzes peptide bonds in small intestine
(pH 7.0-8.0). Aminopeptidase, secreted by intestinal mucosal cells,
also hydrolyzes the bonds
Pepsin, trypsin, chymotrypsin carboxypeptidase, and
aminopeptidase are all examples of proteolytic enzymes, which are
produced in inactive forms (zymogens)
Finally, all amino acids constituting a protein are released and
absorbed through the intestinal wall using active transport process.
Ultimately, the free amino acids enter the bloodstream and distributed
throughout the body
Protein digestion and absorption
The amino acid pool is the total supply of free amino acids
available for use in the human body. The three sources of this pool
are (i) dietary proteins; (ii) protein turnover; (iii) and
biosynthesis of amino acids in the liver
Protein turnover is the repetitive process of degrading and re-
synthesizing proteins in the human body
In a healthy individual, the amount of nitrogen taken into the body
(dietary proteins) is similar to the amount of nitrogen excreted from
the body per day. Such a person is said to be in a state of nitrogen
balance
Two types of nitrogen imbalance are known:
Negative nitrogen balance. Protein degradation exceeds protein
synthesis and the amount of nitrogen in the urine exceeds the amount
of nitrogen ingested
Positive nitrogen balance. Rate of protein synthesis exceeds that
of protein degradation
Amino acid utilization
The amino acid are used in following four ways:
Protein synthesis. About 75% of the free amino acids in a healthy
individual is used for protein synthesis, as proteins are always
needed to replace old tissues (protein turnover) and/or to build new
tissue (growth)
Synthesis of non-protein nitrogen-containing compounds.
Amino acids are used for the synthesis of nitrogen-containing
nonprotein compounds (e.g., purines and pyrimidines of nucleic
acids, the heme of hemoglobin, neurotransmitters such as
acetylcholine and serotonin, the choline and ethanolamine of
phosphoglycerides, and hormones such as epinephrine)
Amino acid utilization
Synthesis of nonessential amino acids. The amino acid are used
to produce nonessential amino acids that are in short supply
Production of energy. Excess amino acids cannot be stored and
therefore degraded in the body. The degradation process is different
for each of the 20 amino acids
Amino acid utilization