Intermediary Metabolism
M.F.Ullah, Ph.D
COURSE TITLE: BIOCHEMISTRY 2
COURSE CODE: BCHT 202
PLACEMENT/YEAR/LEVEL: 2nd Year/Level 4, 2nd Semester
Definition….
Metabolism comprises the entire set of chemical reactions that occur
in a living organism that allow it to grow, reproduce, maintain its
structure and respond to the environment. These chemical reactions
form an intricate network of pathways and cycles which are regulated
depending upon the needs of the cells.
Significance/ Purpose
Metabolism is a highly coordinated cellular activity in which many
multi-enzyme systems (metabolic pathways) cooperate to:
(1) obtain chemical energy by degrading energy-rich nutrients
from the environment;
(2) convert nutrient molecules into the cell’s own characteristic molecules,
including precursors of macromolecules;
(3) polymerize monomeric precursors into macromolecules: proteins, nucleic
acids, and polysaccharides; and
(4) synthesize and degrade biomolecules required for specialized cellular
functions, such as membrane lipids, intracellular messengers
Intermediary metabolism
The term intermediary metabolism is often applied to the combined activities of
all the metabolic pathways occurring in a living organism that in a step wise
manner convert :
a). Precursors into metabolites, products and energy and
b). inter-converts metabolites, products and energy into precursors,
thereby maintaining the structural and functional integrity of a cell.
Example: A diet containing carbohydrate, protein and fat undergoes following metabolic
pathways collectively called intermediary metabolism
Starch
Dietary proteins
Dietary fats
Glucose
Intermediates
Amino acids
Intermediates
Fatty acids
Intermediates
Glucose
Amino acids
Fatty acids
Glycogen
Cellular Proteins
Membrane lipids
Metabolic Pathway
The sum of all the chemical
transformations taking place in a cell, occurs
a series of enzyme-catalyzed reactions that constitute
through
metabolic pathways. Each of the consecutive steps in a metabolic pathway from
starting compound (precursor) to the final end product produce
intermediate called metabolites.
Example: Glycolysis is a metabolic
pathway and Fructose-1,6-bisP is one of it
metabolite
Metabolic pathways can be linear
Such as glycolysis or cyclic such as
TCA
In general metabolism is classified
into two types of processes:
1. Catabolic processes
2. Anabolic processes
metabolic
Catabolism is the degradative phase of metabolism
in which organic nutrient molecules (carbohydrates,
fats, and proteins) are converted into smaller, simpler
end products (such as lactic acid, CO2, NH3).
Catabolic pathways release energy, some of which is
conserved in the formation of ATP and reduced
electron carriers (NADH, NADPH, and FADH2); the
rest is lost as heat.
Example:
Carbohydrate catabolism
Energy
Glycogen
Glucose
Pyruvate
Acetyl CoA
Co2+ H2O
Anabolism is the biosynthetic phase of metabolism in which small,
simple precursors are built up into larger and more complex
molecules, including lipids, polysaccharides, proteins, and nucleic
acids.
Anabolic reactions require an input of energy, generally in the form
of the phosphoryl group transfer potential of ATP and the reducing
power of NADH, NADPH, and FADH2
Example:
Carbohydrate Anabolism
Pyruvate
Energy
Oxaloacetate
Glucose
Glycogen
Relationships between catabolic and anabolic
Pathways:
Catabolic pathways deliver chemical energy
in the form of ATP, NADH, NADPH, and FADH2.
These energy carriers are used in anabolic
pathways to convert small precursor
molecules into cell macromolecules.
In general, catabolic pathways are convergent and
anabolic pathways are divergent
Carbohydrate catabolism
Glycogenolysis: glycogen → glucose 1-phosphate → blood glucose
Glycolysis: glucose → pyruvate
Carbohydrate anabolism
Gluconeogenesis: citric acid cycle intermediates → glucose
Glycogen synthesis: glucose 6-phosphate → glucose 1-phosphate → glycogen
Integration of Metabolism:
The metabolic pathways for carbohydrate, protein and fat are
integrated and the point of integration is served by certain common
metabolites (intermediates). It is through these points of integration
feeder pathways often act to replenish the exhausting metabolites
of one pathway by utilizing the common metabolic intermediate
produced by the other pathway.
Metabolic Integration
Carbohydrate
metabolism
Fat
metabolism
Protein
metabolism
Fat
metabolism
Protein
metabolism
Protein
metabolism
Protein
metabolism
Protein
metabolism
Protein
metabolism
Lipid Metabolic Reactions
Biomolecules & Energy relationship
DIETARY FUELS
The major fuels we obtain from our diet are carbohydrates,
proteins, and fats. When these fuels are oxidized to CO2 and
H2O in our cells, energy is released by the transfer of electrons
to O2. The energy from this oxidation process generates heat
and adenosine triphosphate (ATP) . Carbon dioxide travels in the
blood to the lungs, where it is expired, and water is excreted in
urine, sweat, and other secretions. Although the heat that is
generated by fuel oxidation is used to maintain body
temperature, the main purpose of fuel oxidation is to generate
ATP. ATP provides the energy that drives most of the energyconsuming processes in the cell, including biosynthetic
reactions, muscle contraction, and active transport across
membranes. As these processes use energy, ATP is converted
back to adenosine diphosphate (ADP) and inorganic phosphate
(Pi).
The oxidation of fuels to generate ATP is called respiration . Before
oxidation, carbohydrates are converted principally to glucose, fat to fatty
acids, and protein to amino acids.
The pathways for oxidizing glucose, fatty acids, and amino acids have
many features in common. They first oxidize the fuels to acetyl CoA, a
precursor of the tricarboxylic acid (TCA) cycle. The TCA cycle is a series of
reactions that completes the oxidation of fuels to CO2 .
Electrons lost from the fuels during oxidative reactions are transferred to
O2 by a series of proteins in the electron transport chain. The energy of
electron transfer is used to convert ADP and Pi to ATP by a process
known as oxidative phosphorylation.
In discussions of metabolism and nutrition, energy is often expressed in
units of kilocalorie (kcal). Energy is also expressed in kilojoules. One
kilocalorie equals 4.18 kilojoules (kJ).
Carbohydrates
The major carbohydrates in the human diet are starch, sucrose, lactose, fructose, and
glucose. The polysaccharide starch is the storage form of carbohydrates in plants. Sucrose
(table sugar) and lactose (milk sugar) are disaccharides, and fructose and glucose are
monosaccharides. Digestion converts the larger carbohydrates to monosaccharides, which
can be absorbed into the bloodstream. Glucose, a monosaccharide, is the predominant
sugar in human blood.
Oxidation of carbohydrates to CO2 and H2O in the body produces approximately 4 kcal/g .
In other words, every gram of carbohydrate we eat yields approximately 4 kcal of energy.
Note that carbohydrate molecules contain a significant amount of oxygen and are already
partially oxidized before they enter our bodies.
Proteins
Proteins are composed of amino acids that are joined to form linear chains. In
addition to carbon, hydrogen, and oxygen, proteins contain approximately 16%
nitrogen by weight. The digestive process breaks down proteins to their
constituent amino acids, which enter the blood. The complete oxidation of
proteins to CO2, H2O, and NH4 in the body yields approximately 4 kcal/g.
Our major fuel store is adipose triacylglycerol (triglyceride), a lipid more
commonly known as fat.
Fats
Fats are lipids composed of triacylglycerols (also called triglycerides). A triacylglycerol
molecule contains 3 fatty acids esterified to one glycerol moiety. Fats contain much
less oxygen than is contained in carbohydrates or proteins. Therefore, fats are more
reduced and yield more energy when oxidized. The complete oxidation of
triacylglycerols to CO2 and H2O in the body releases approximately 9 kcal/g, more
than twice the energy yield from an equivalent amount of carbohydrate or protein.
A case study
Mr. Steve recently discovered that he has put on much weight during the last 2 months.
He was concerned about his health and so he went to Dr. Smith, a dietician for an advice.
Dr. Smith advised him to restrict his fat, carbohydrate and protein intake to 50% of the
current intake.
An analysis of Mr. Steve’s current diet showed that he ate 300 g carbohydrate, 60 g
protein and 80 g fat each day. Calculate the caloric restriction imposed on Mr. Smith by
his dietician.
Caloric restriction is the number of calories permitted to be consumed
STEP 1:Considering the current diet to be 100% , reduction by 50% will give dietary
restriction of: 100% - 50% = 50%
STEP 2: Now calculate 50% of each of the content of the current diet to get the
recommended diet
Carbohydrate : Current content = 300g
Recommended - 50/100 x 300 = 150g
Protein : Current content 60 g
Recommended – 50/100x60= 30 g
Fat: Current content= 80 g
Recommended- 50/100x80= 40g
STEP 3: Now calculate the calories from each of the recommended content and add up:
Carbohydrate: 300x4= 1200 Kcal
(4Kcal/g)
Protein : 30x 4= 120 Kcal
(4 Kcal/g)
Fat: 40x9= 360 Kcal
(9 Kcal/g)
Total calories= …….. Kcal (permitted to be consumed or caloric restriction)
In Kjoules : ……..x 4.18=2570 KJ
(1 Kcal=4.18 KJ)
Suggested readings
Harper's Illustrated Biochemistry, 28e
Robert K. Murray, David A Bender, Kathleen M. Botham, Peter J. Kennelly, Victor W. Rodwell, P. Anthony Weil
Copyright © 2009 by The McGraw-Hill Companies, Inc
Available in the University Library
Marks’ Basic Medical Biochemistry: A Clinical Approach
Lippincott Wiliams & Wilkins