Overview of Metabolism

Note worthy terms:

Pyruvate: The conjugate base, CH3COCOO-, is a key intermediate in several metabolic

pathways which will eventually form pyruvic acid with the reaction with Acetyl-CoA.

Acetyl-CoA: A molecule that participates in many biochemical reactions in protein, carbohydrate

and lipid metabolism.Its main function is to deliver the acetyl group to the citric acid cycle
(Krebs cycle) to be oxidized for energy production.
*CoA signifies Coenzyme A

Acetyl-CoA is generated either by oxidative decarboxylation of pyruvate from glycolysis

Pyruvic acid can be made from glucose through glycolysis, converted back
to carbohydrates (such as glucose) via gluconeogenesis, or to fatty acids through a reaction
with acetyl-CoA. It can also be used to construct the amino acid alanine and can be converted
into ethanol or lactic acid via fermentation.
Pyruvic acid supplies energy to cells through the citric acid cycle (also known as the Krebs
cycle) when oxygen is present (aerobic respiration), and alternatively ferments to
produce lactate when oxygen is lacking (fermentation)
Electron transport chain (ETC): It is a series of complexes that transfer
electrons from electron donors to electron acceptors via redox (both reduction and oxidation
occurring simultaneously) reactions, and couples this electron transfer with the transfer of
protons (H+ions) across a membrane.

Metabolism
It is a term that is used to describe all chemical reactions involved in maintaining the living state
of the cells and the organism.
Metabolism is organized by a series of metabolic pathways.
It is generally defined by two categories namely:
i)Catabolism
ii)Anabolism
Metabolic pathways are specific forms of metabolism, these allow the basic chemicals from
nutrition to be transformed through a series of steps into another chemical, by a sequence of
enzymes.
The processes of making and breaking down glucose molecules are both examples of metabolic
pathways. A metabolic pathway is a series of connected chemical reactions that feed one
another. The pathway takes in one or more starting molecules and, through a series of
intermediates, converts them into products.

Metabolic pathways can be broadly divided into two categories based on their effects.
Photosynthesis, which builds sugars out of smaller molecules, is a "building up," or anabolic
pathway. In contrast, cellular respiration breaks sugar down into smaller molecules and is a
"breaking down," or catabolic pathway.

Anabolic pathways build complex molecules from simpler ones and typically need an input of
energy. Building glucose from carbon dioxide is one example. Other examples include the
synthesis of proteins from amino acids, or of DNA strands from nucleic acid building blocks
(nucleotides). These biosynthetic processes are critical to the life of the cell, take place
constantly, and use energy carried by ATP and other short-term energy storage molecules.

Catabolic pathways involve the breakdown of complex molecules into simpler ones and
typically release energy. Energy stored in the bonds of complex molecules, such as glucose and
fats, is released in catabolic pathways. It's then harvested in forms that can power the work of the
cell (for instance, through the synthesis of ATP).

Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions
that require energy. These reactions also are coupled with those that release energy.
Enzymes acts as catalysts and regulators of metabolic pathways in response to any change in the
cell's environment.

Catabolism - the breakdown of molecules to obtain energy

Anabolism - the synthesis of all compounds needed by the cells

Metabolism is closely linked to nutrition and the availability of nutrients. Bioenergetics is a term
which describes the biochemical or metabolic pathways by which the cell ultimately obtains
energy. Energy formation is one of the vital components of metabolism.
Nutrition , metabolism and energy are closely related to one another.
Nutrition is a science that deals with the relation of food substance to living things. In the study
of nutrition, the following items must be considered:
a) bodily requirement for various substances.
b) function in body.
c) amount needed.
d) level below which poor health results.

Essential foods supply energy (calories) and supply the necessary chemicals which the body
itself cannot synthesize. Food provides a variety of substances that are essential for the building,
upkeep, and repair of body tissues, and for the efficient functioning of the body.
Nutrition is the key to metabolism. The pathways of metabolism rely upon nutrients that they
breakdown in order to produce energy. This energy in turn is required by the body to synthesize
new proteins, nucleic acids (DNA, RNA) etc.
The diet needs essential nutrients like carbon, hydrogen, oxygen, nitrogen, phosphorus, sulfur,
and around 20 other inorganic elements. The major elements are supplied in carbohydrates,
lipids, and protein. In addition, vitamins, minerals and water are necessary.

Metabolic Flux

Flux through all pathways is remarkably balanced and adaptable.

Metabolic flux is the passage of a metabolite through a reaction system over time.
Metabolite is a general term for the product of Metabolism.

Carbohydrate Metabolism
There are 3 forms of Carbohydrates that we intake:
i) Starch
ii) Cellulose
iii) Sugar

Starch and sugar are major and essential sources of energy for humans. Cellulose furnishes bulk
in the diet.

Body tissues depend on glucose for all activities. Carbohydrates and sugars yield glucose by
digestion or metabolism.
Many cells, including most of the cells in your body, get energy from glucose in a process
called cellular respiration. During this process, a glucose molecule is broken down gradually, in
many small steps.

The overall reaction for the combustion of glucose is written as:

C6H12O6 + 6O2 6CO2 + 6H2O + energy

Energy in the form of ATP ( Adenosine Triphosphate)
ATP is the energy currency of the cell.
Breaking down glucose releases energy, which is captured by the cell in the form of ATP
which is a small molecule that gives cells a convenient way to briefly store energy. This reaction
is the breakdown of glucose in cellular respiration.

Sugars like glucose are made by plants in a process called photosynthesis. In photosynthesis,
plants use the energy of sunlight to convert carbon dioxide gas into sugar molecules.
Photosynthesis takes place in many small steps, but its overall reaction is just the cellular
respiration reaction flipped backwards.

6CO2 + 6H2O + energy C6H12O6 + 6O2

Protein Metabolism

About 1/3 of all protein domain conserved across all kingdoms are devoted for metabolism. The
likes of transcription, translation and replication.

Proteins are the main tissue builders in the body. They are part of every cell in the body. Proteins
help in cell structure, functions, haemoglobin formation to carry oxygen, enzymes to carry out
vital reactions and a myriad of other functions in the body. Proteins are also vital in supplying
nitrogen for DNA and RNA genetic material and energy production.

Proteins are necessary for nutrition because they contain amino acids. Among the 20 or more
amino acids, the human body is unable to synthesize 8 and these are called essential amino acids.

The essential amino acids include:

Lysine tryptophan methionine

Leucine isoleucine phenylalanine

Valine threonine

Fat Metabolism

Fats are concentrated sources of energy. They produce twice as much energy as either
carbohydrates or protein on a weight basis.

The functions of fats include:

- helping to form the cellular structure.

- forming a protective cushion and insulation around vital organs.

- helping absorb fat soluble vitamins.

- providing a reserve storage for energy.

Vitamin and Mineral Metabolism

The minerals in foods do not contribute directly to energy needs but are important as body
regulators and play a role in metabolic pathways of the body as they are essential
constituents in many vital substances within the body. More than 50 elements are found in
the human body.

A MINERAL is rather loosely defined as any element not normally a part of the structures of
carbohydrates, proteins, and fats.

Important minerals include:

Calcium Phosphorus Iron

Sodium Potassium

Vitamins are essential organic compounds that the human body cannot synthesize by itself and
must therefore, be present in the diet.The term vitamin (vital amines) was coined by Casmir
Funk from the Latin vita meaning "life" (essential for life) and amine because he thought that all
of these compounds contained an amine functional group.

Vitamins particularly important in metabolism include:

Vitamin A : The yellow and green pigments found in vegetables are called carotenes which are
pro vitamins and are converted into Vitamin A. The role of vitamin A in vision.

Vitamin B2 (riboflavin) : It is widely distributed in many foods. Riboflavin is used to form a

coenzyme FAD (Flavin Adenine Dinucleotide) important in the utilization of oxygen in the cells.

Niacin or nicotinic acid : It is also in the B complex of vitamins. Nicotinic acid was first obtained
from the alkaloid nicotine in tobacco and was later found in many plant and animal tissues as
niacin. Niacin together with nicotinamide it makes up the group known as vitamin B3 complex.

Note: Nicotinamide is a part of the important coenzyme, Nicotinamide Adenine Dinucleotide

(NAD). This NAD+ coenzyme is important during biological oxidations

Pantothenic Acid (Vitamin B5) : It is used to synthesize coenzyme-A (CoA), as well as to

synthesize and metabolize proteins, carbohydrates, and fats.

Carbon Catabolism
What is Catabolism ?
- it is the breakdown of molecules into simpler ones. This process produces the energy needed
for physical activity from a cellular level all the way up to any movement of your body
Catabolism releases energy during the breakdown process of organic nutrients, and this energy is
stored inside molecules of adesonine triposphate, also called ATP, in the body
Catabolism also releases the energy needed for your body to maintain the correct temperature.

Basic Sources of Energy of the body

- Protein
- Carbohydrates
- Fat
The body can either immediately break them down for energy, or it can store them for later use:
protein in the form of muscle, fat in the form of body fat, and carbohydrates in the form of
glycogen, which is a starch-like structure.
3 stages of Catabolism
Stage 1: carbohydrates, fats, and proteins are broken down into their individual monomer units:
carbohydrates into simple sugars, fats into fatty acids and glycerol, and proteins into amino
acids. One part of stage I of catabolism is the breakdown of food molecules by hydrolysis
reactions into the individual monomer units—which occurs in the mouth, stomach, and small
intestine—and is referred to as digestion
Stage 2: the monomer units (or building blocks) are further broken down through different
reaction pathways, one of which produces ATP, to form a common end product that can then be
used in stage III this stage is referred to as glycolysis
Stage 3: the end product in previous step is oxidized to produce even more ATP for energy
production -this stage is referred to as beta oxidation.

Stage 1: Digestion
Digestion is a form of catabolism that is often divided into two processes based on how food is
broken down: mechanical and chemical digestion.

The term mechanical digestion refers to the physical breakdown of large pieces of food into
smaller pieces which can subsequently be accessed by digestive enzymes.

In chemical digestion, enzymes break down food into the small molecules the body can use.
During digestion, carbohydrates are broken down into monosaccharides, proteins are broken
down into amino acids, and triglycerides are broken down into glycerol and fatty acids. Most of
the digestion reactions occur in the small intestine.
Stage 2 : Glycolysis
Glycolysis literally means “Splitting Sugars“.
In glycolysis, glucose (a six carbon sugar) is split into two molecules of a three-carbon sugar.
Glycolysis yields two molecules of ATP (free energy containing molecule), two molecules of
Pyruvic acid and two “high energy” electron carrying molecules of NADH.
Glycolysis is divided into two phases: Preparative phase (Step 1 to 5) and Pay off Phase (Step 6
to 10).
Preparative Phase:
This is the first phase of Glycolysis. In this Glucose is converted into Glyceraldehyde-3-
Phosphate and DHAP (Dihydroxy Acetone Phosphate). This phase contains 5 Steps.

Step 1: Phosphorylation :
The enzyme Hexokinase phosphorylates (adds a phosphate group to) glucose in the cell’s
cytoplasm. In the process, a phosphate group from ATP is transferred to glucose producing
glucose 6-phosphate.
Glucose (C6H12O6) + hexokinase + ATP → ADP + Glucose 6-phosphate (C6H11O6P1)

Step 2: Isomerization :
The enzyme phosphoglucoisomerase converts glucose 6-phosphate into its isomer fructose 6-
phosphate. Isomers have the same molecular formula, but the atoms of each molecule are
arranged differently.
Glucose 6-phosphate (C6H11O6P1) + Phosphoglucoisomerase→ Fructose 6-phosphate
(C6H11O6P1)

Step 3: Phosphorylation:
The enzyme phosphofructokinase uses another ATP molecule to transfer a phosphate group to
Fructose-6-phosphate to form fructose-1,6-bisphosphate.
Fructose 6-phosphate (C6H11O6P1) + Phosphofructokinase + ATP →
ADP + Fructose 1, 6-bisphosphate (C6H10O6P2)
Step 4: Condensation:
The enzyme aldolase splits Fructose-1,6-bisphosphate into two sugars that are isomers of each
other. These two sugars are Dihydroxyacetone phosphate (DHAP) and Glyceraldehyde-3-
phosphate.
Fructose 1, 6-bisphosphate (C6H10O6P2) + aldolase →
Dihydroxyacetone phosphate (C3H5O3P1) + Glyceraldehyde phosphate (C3H5O3P1)

Step 5:Isomerization:
The enzyme triose phosphate isomerase rapidly inter-converts the molecules dihydroxyacetone
phosphate (DHAP) into glyceraldehyde-3-phosphate. Glyceraldehyde phosphate is removed as
soon as it is formed to be used in the next step of glycolysis.
Dihydroxyacetone phosphate (C3H5O3P1) → Glyceraldehyde phosphate (C3H5O3P1)
Net result for steps 4 and 5:
Fructose 1, 6-bisphosphate (C6H10O6P2) ↔ 2 molecules of Glyceraldehyde phosphate
(C3H5O3P1)

Pay-off Phase:
This is the second phase of Glycolysis. In this phase Glyceraldehyde-3-Phosphate is
converted into Pyruvate molecules. This phase have 5 steps.

Step 6: Dehydrogenation:
The enzyme triose phosphate dehydrogenase serves two functions in this step. First the enzyme
transfers a hydrogen (H-) from Glyceraldehyde-3-phosphate to the oxidizing agent Nicotinamide
Adenine Dinucleotide (NAD+) to form NADH. Next Triose phosphate dehydrogenase adds a
phosphate (P) from the cytosol to the oxidized glyceraldehyde-3-phosphate to form 1, 3-
bisphosphoglycerate. This occurs for both molecules of glyceraldehyde-3-phosphate produced in
step 5.

A. Triose phosphate dehydrogenase + 2 H- + 2 NAD+ → 2 NADH + 2 H+

B. Triose phosphate dehydrogenase + 2 P + 2 glyceraldehyde phosphate (C3H5O3P1)→ 2
molecules of 1,3-bisphosphoglycerate (C3H4O4P2)

Step 7: Substrate level Phosphorylation:

The enzyme phosphoglycerokinase transfers a P from 1,3-bisphosphoglycerate to a molecule of
ADP to form ATP. This happens for each molecule of 1,3-bisphosphoglycerate. The process
yields two 3-phosphoglycerate molecules and two ATP molecules.
2 molecules of 1,3-bisphoshoglycerate (C3H4O4P2) + phosphoglycerokinase + 2 ADP → 2
molecules of 3-phosphoglycerate (C3H5O4P1) + 2 ATP

Step 8: Dehydration (Intramolecular rearrangement):

The enzyme phosphoglyceromutase relocates the Phosphate from 3-phosphoglycerate from the
third carbon to the second carbon to form 2-phosphoglycerate.
2 molecules of 3-Phosphoglycerate (C3H5O4P1) + phosphoglyceromutase → 2 molecules of 2-
Phosphoglycerate (C3H5O4P1)

Step 9 : Enolyzation :
The enzyme Enolase removes a molecule of water from 2-phosphoglycerate to form Phospho
Enol Pyruvic acid (PEP). This happens for each molecule of 2-phosphoglycerate.
2 molecules of 2-Phosphoglycerate (C3H5O4P1) + enolase → 2 molecules of
phosphoenolpyruvic acid (PEP) (C3H3O3P1)

Step 10: Substrate level Phosphorylation:

The enzyme Pyruvate kinase (PK) transfers a Phosphate from PEP to ADP to form Pyruvic acid
and ATP. This happens for each molecule of PEP. This reaction yields 2 molecules of Pyruvic
acid and 2 ATP molecules. Pyruvate Kinase is a Potassium Containing Enzyme
2 molecules of PEP (C3H3O3P1) + pyruvate kinase + 2 ADP → 2 molecules of pyruvic acid
(C3H4O3) + 2 ATP

Stage 3 : Beta Oxidation

Beta-oxidation is the process by which fatty acids, specifically saturated fatty acids, are broken
down for use in energy production.

Often takes place inside the mitochondrial matrix, although it can also occur in organelles called
peroxisomes.

The main components of beta oxidation process are saturated fatty acids, a molecule called
coenzyme A, also called CoA and also enzymes. The other components are the molecules of
water, ATP, FAD+, and NAD+.

Enzymes are proteins that speed up chemical reactions.

Steps of Beta-Oxidation
The main process of beta-oxidation is that the fatty acids are looking to change themselves, or be
broken down. Before that, the enzyme, acyl-CoA ligase, uses adenosine triphosphate, or ATP, to
join a fatty acid with CoA. They form a new happy molecule called acyl-CoA. It is as acyl-CoA
that the fatty acids are able to broken down in the mitochondrial matrix.

There are four main steps,or acts, in beta-oxidation:

- Loss of hydrogens
- Addition of water
- Loss of another hydrogen
- Addition of another CoA

Cellular Respiration
Basically, ATP (adenosine triphosphate) serves as the main energy currency of the cell.
Living organisms, including plants, animals, and microorganisms, generate their own energy in a
process called cellular respiration. Interestingly depending on the type of precursor for ATP
production, organisms can be classified into two:

 Organisms that utilize oxygen in the process are called as “aerobic”.

 And those who do not are described as “anaerobic”.

Cellular respiration (regardless whether it is aerobic or anaerobic) provides the required

amount of ATP for living organisms. The energy present in the form of ATP can then be utilized
to drive various intra-cellular physiological processes like the transport of molecules across cell
membranes and the synthesis of bio-molecules.

Aerobic Cellular Respiration

Aerobic respiration is the type of cellular respiration that requires the presence of oxygen.
Among all the types of cellular respiration it is the most efficient. Plants and animals carry out this
kind of respiration; plants obtain the precursor molecules from photosynthesis while animals
obtain them from the food they eat (i.e. plants/animals).

Overall chemical reaction of cellular respiration equation is simplified as:

C6H12O6+ 2NAD+ + 2ADP + 2P → 2pyruvic acid, (CH3(C=O)COOH + 2ATP + 2NADH + 2H+

Stages of Cellular Respiration

1. Glycolysis
 The first metabolic pathway during cellular respiration is glycolysis. Coming from the
Greek word “glyk” which means “sweet” and “lysis” which means “dissolution “,
glycolysis is the breakdown of one molecule of glucose (six-carbon sugar) into two
molecules of pyruvate, a three-carbon molecule, and NAD+ is converted to NADH

 As shown in the above diagram, glycolysis takes place in the cytosol

 While the above equation shows that glycolysis produces two ATP molecules, four
molecules are actually produced during the entire process. However, two molecules are
consumed during the preparatory phase, hence, resulting to a net of just two ATP
molecules.

2. Pyruvate Oxidation

After glycolysis, there is a so-called “link reaction” that occurs. Such reaction is
the oxidative decarboxylation of pyruvate by the Pyruvate dehydrogenase complex (PDC).
In simpler terms, the pyruvate from glycolysis is oxidized to two-carbon molecule bound
to Coenzyme A (acetyl CoA), one molecule of NADH (nicotinamide adenine
dinucleotide), and one molecule of carbon dioxide.

3. Krebs Cycle

Also called as the Tricarboxylic Acid (TCA) cycle, or simply the Citric Acid cycle, the
Krebs cycle (identified by Hans Adolf Krebs) is an 8-step process that involves 18 different
enzymes.

 The Krebs cycle, which occurs in the matrix of the mitochondrion, includes a series of
oxidation-reduction reactions that result in the oxidation of the acetyl group to two
carbon dioxide molecules.
 During one cycle, there is a net of 3 NADH, 1 FADH2(flavin adenine dinucleotide),
GTP (guanosine triphosphate, may be alternatively used to produce ATP), and carbon
dioxide.
 Hence, from one glucose molecule (that formed 2 pyruvate), a total of 6 NADH, 2
FADH2and 2 ATP molecules are produced.
 Note that the goal of the Krebs cycle is to generate high energy electrons from carbon
sources. Also notice that the process itself does not generate huge amounts of ATP and
does not use oxygen as a precursor molecule.
 Instead it uses the electrons from acetyl CoA to form NADH and FADH2.

4. Electron Transport Chain and Oxidative Phosphorylation

 The final pathway in the cellular respiration is comprised of the electron transport chain
and oxidative phosphorylation which both occur in the inner membrane of the
mitochondrion.

 The NADH and FADH2 made in other steps deposit their electrons in the electron
transport chain, turning back into their "empty" forms (NAD+ and FAD+ ). As
electrons move down the chain, energy is released and used to pump protons out of
the matrix, forming a gradient. Protons flow back into the matrix through an
enzyme called ATP synthase, making ATP. At the end of the electron transport
chain, oxygen accepts electrons and takes up protons to form water.

 Overall ETC produces water, NAD+ and FAD+ (which are both recycled back to
glycolysis and Krebs cycle), and up to 34 ATP per one molecule of glucose!

In total the resulting product of aerobic cellular respiration from a single glucose molecule
can be up to 38 ATP. However some organisms can only produce 34 to 36 because they have a
different precursor molecule.

Role of Oxygen in the Process

Oxygen is an essential molecule in cellular respiration. Basically, oxygen can be found at

the end of the ETC (during aerobic respiration) where it accepts electrons while picking up protons
in order to produce water molecules.

 Because of this, oxygen is also called as the “final electron acceptor”. When oxygen
levels are depleted, electrons will be simply dispersed and the electron transport chain
will discontinue.
 Of course no ATP will be produced, causing the cease of some physiological functions
in the cell.
Anaerobic Cellular Respiration

This process occurs just like the typical cellular reaction (same glycolytic and Krebs cycle
pathway) but only differs because it is used by organisms like bacteria and archaea where oxygen
is not the final electron acceptor. Rather, these organisms use sulfates or nitrates instead.

 It is important to note uses other molecules to complete the cycle as the organism will
die in the presence of oxygen.
 Unlike aerobic respiration that occurs in the mitochondria, aerobic respiration happens
in the cytosol.
 The process of anaerobic respiration generates only 2 ATP per glucose molecule.