METABOLISM

METABOLISM
Sum total of all chemical reactions in a living organism
Source of energy for the functioning of the human body
Also needed for many of the cellular processes such as
protein synthesis, DNA replication, RNA transcription,
and membrane transport

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SUBTYPES OF METABOLIC REACTIONS
Catabolism: All metabolic reactions in which large
biochemical molecules are broken down to smaller ones
 Usually energy is released in these reactions
 Example: Oxidation of glucose

Anabolism: All metabolic reactions in which small

biochemical molecules are joined to form larger ones
 Usually require energy
 Example: Synthesis of proteins

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METABOLISM
Metabolism
involves
Catabolic reactions
that break down
large, complex
molecules to
provide energy and
smaller molecules.
Anabolic reactions
that use ATP energy
to build larger
molecules.

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FIGURE 23.1 - THE PROCESSES OF CATABOLISM
AND ANABOLISM

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STAGES OF METABOLISM
Catabolic reactions are organized as
Stage 1: Digestion and hydrolysis break down
large molecules to smaller ones that
enter the bloodstream.
Stage 2: Degradation breaks down molecules to
two- and three-carbon compounds.
Stage 3: Oxidation of small molecules in the citric
acid cycle.
Stage 4 Oxidation of small molecules in the electron transport chain to provide
ATP energy
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 Energy needed to run the human body is obtained from
food via a multistep process involving several different
catabolic pathways
There are four general stages in the biochemical energy
production process:
 Stage 1: Digestion
 Stage 2: Acetyl group formation
 Stage 3: Citric acid cycle
 Stage 4: Electron transport chain and oxidative phosphorylation

Each stage also involves numerous reactions

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STAGES OF
CATABOLISM
DIGESTION
▪The biochemical process by which food molecules through
hydrolysis, are broken down into simpler chemical units that
can be used by cells for their metabolic needs.
▪The first stage of the processing of food products
CARBOHYDRATE DIGESTION PROCESS
Digestion: Breakdown of food molecules by hydrolysis into simpler
chemical units that can be used by cells in their metabolic processes
Carbohydrate digestion - Begins in the mouth
 Salivary -amylase catalyzes the hydrolysis of -glycosidic linkages in starch
and glycogen to produce smaller polysaccharides and disaccharide maltose
 A small amount of carbohydrate digestion occurs in the mouth because food is
swallowed quickly

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STAGE 1: DIGESTION
Begins in mouth (saliva contains starch-digesting
enzymes), continues in the stomach (gastric juices), and is
completed in small intestine
 Results in small molecules that can cross intestinal membrane into the blood
stream

End products which are absorbed and transported to

blood cells:
 Glucose and monosaccharides from carbohydrates
 Amino acids from proteins
 Fatty acids and glycerol from fats and oils

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CARBOHYDRATE DIGESTION PROCESS
Small amount of carbohydrate is digested in the stomach
 Salivary -amylase gets inactivated because of stomach acidity
 No carbohydrate-digesting enzymes are present

Small intestine - Primary site for carbohydrate digestion

 Pancreatic -amylase breaks down polysaccharide chains into disaccharide maltose

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CARBOHYDRATE DIGESTION PROCESS
Final step occurs on the outer membranes of intestinal mucosal cells
 Disaccharidase enzymes convert disaccharides to monosaccharides
 Maltase - Converts maltose to glucose
 Sucrase - Converts sucrose to glucose and fructose
 Lactase - Converts lactose to glucose and galactose
 Carbohydrate digestion products (glucose, galactose, and fructose) are absorbed into
the bloodstream through the intestinal wall

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CARBOHYDRATE DIGESTION PROCESS
 Intestinal villi are rich in blood capillaries into which the monosaccharides are actively
transported
 Protein carriers mediate the passage of the monosaccharides through cell membranes

Galactose and fructose are converted to products of glucose

metabolism in the liver

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STAGE 3: CITRIC ACID CYCLE
• Takes place inside the mitochondria
• Acetyl group is oxidized to produce CO2 and
energy
• Some energy produced in this stage is lost in the
form of heat
– Most energy is trapped in reduced coenzymes NADH
and FADH2
• The carbon dioxide we exhale comes primarily
from this stage

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 STAGE 1: DIGESTION OF CARBOHYDRATES
In Stage 1, the
digestion of
carbohydrates
Begins in the mouth where
salivary amylase
breaks down polysaccharides
to smaller
polysaccharides
(dextrins), maltose, and
some glucose.
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It continues in the
small intestine where
pancreatic
amylase hydrolyzes
dextrins to maltose
and glucose.
The final step in
carbohydrate digestion
occurs on the other
membrane of intestinal
mucosal cells where the
enzymes that convert
disaccharide to
monosaccharides are
located.
Hydrolysis of
maltose, lactose,
and sucrose to
monosaccharides,
mostly glucose,
which enter the
bloodstream
through intestinal
wall (villi) for
transport to the
cells.
Absorption is by
active transport.
After their absorption
into the bloodstream,
the monosaccharides
are transported to the
liver to be rapidly
converted by a
metabolic pathway
called

GLYCOLYSIS
STAGE 2: GLYCOLYSIS
▪Is a metabolic pathway
that uses glucose, a
digestion product.
▪Degrades six-carbon
glucose molecules to
three-carbon. pyruvate
molecules.
▪Is an anaerobic (no
oxygen) process.
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GLYCOLYSIS: ENERGY-INVESTMENT
In reactions 1-5 of
glycolysis,
Energy is required to
add phosphate
groups to glucose.
Glucose is converted
to two three-carbon
molecules.
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GLYCOLYSIS: ENERGY-INVESTMENT
Step 1: Phosphorylation using
ATP
Formation of Glucose-6-
Phosphate
Phosphate group came from ATP
Hexokinase- require Mg2+ to
catalyze the reaction.
The reactions requires energy
(from breakdown of ATP)
GLYCOLYSIS: ENERGY-INVESTMENT
Step 2: Isomerization:
Formation of Fructose-6-
Phosphate.
C1 is no longer part of the ring
structure.
 GLYCOLYSIS: ENERGY-INVESTMENT
Step 3: Phosphorylation Using
ATP

Formation of Fructose 1,6-

biphosphate.
Requires Expenditure of Energy
from ATP.
Here, it commits the original
glucose molecule to the glycolysis
pathway--
 GLYCOLYSIS: ENERGY-INVESTMENT

Step 4: Cleavage
Formation of 2 Triose
Phosphate.
Here begins the 3-Carbon
Stage of Glycolysis.
Fructose-1,6-biphosphate is
unsymmetrical if being split
yielding two not identical
trioses.
GLYCOLYSIS: ENERGY-INVESTMENT
Step 5: Isomerization
Formation of Glyceraldehyde
3-Phosphate (the only
produced)

Dihydroxyacetone phosphate
can be readily converted to
Glyceraldehyde 3-Phosphate
by isomerization process
catalyzed by
triosephosphateisomerase
GLYCOLYSIS: ENERGY-PRODUCTION
In reactions 6-10
of glycolysis,
energy is
generated as
Sugar phosphates
are cleaved to
triose phosphates.
Four ATP molecules
are produced.
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GLYCOLYSIS: REACTIONS 6-10
Step 6: Oxidation and
Phosphorylation using Pi
Formation of 1,3-biphosphoglycerate
A Phosphate group is added to
Glyceraldehyde 3-Phosphate thru a
rxn catalyzed by Glyceraldehyde-3-
phosphate-dehydrogenase
GLYCOLYSIS: REACTIONS 6-10
Step 6: Oxidation and
Phosphorylation using Pi
The newly added phosphate group in
1,3-biphosphoglycerate is a high-
energy phosphate group.
The source of added phosphate came
from Inorganic Phosphate not from
ATP
GLYCOLYSIS: REACTIONS 6-10
Step 7: Phosphorylation of
ADP
Formation of 3
Phosphoglycerate
The diphosphate specie is
converted back to
monophosphate specie.
ADP to form ATP
2 ATP molecules are
produced
 GLYCOLYSIS: REACTIONS 6-10
Step 8: Isomerization
Formation of 2-
Phosphoglycerate
Phosphate group of 3-
Phosphoglycerate is
moved form C3 to C2.
The reaction is catalyzed
by
phosphoglyceratemutase
GLYCOLYSIS: REACTIONS 6-10
Step 9: Dehydration
Formation of
Phosphoenolpyruvate
An alcohol dehydration
reaction which requires
enolase
The result is another
compound containing a high-
energy phosphate group.
GLYCOLYSIS: REACTIONS 6-10
Step 10: Phosphorylation
of ADP

Formation of Pyruvate
The phosphate group is
transferred to ADP to form
ATP and pyruvate.
GLYCOLYSIS: OVERALL REACTION
In glycolysis,
Two ATP add phosphate to glucose and fructose-6-phosphate.
Four ATP are formed in energy-generation by direct transfers of phosphate
groups to four ADP.
There is a net gain of 2 ATP and 2 NADH.

C6H12O6 + 2ADP + 2Pi + 2NAD+

Glucose
2C3H3O3- + 2ATP + 2NADH + 2H2O
Pyruvate
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There is a net gain of TWO ATP molecules for
every glucose molecule converted into two
pyruvates.
 PATHWAYS FOR PYRUVATE

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THE FATE OF PYRUVATE

Figure 8.7
The TCA Cycle

Figure 8.11
THE CITRIC ACID CYCLE
The citric acid cycle is a
series of reactions that
connects the intermediate
acetyl CoA from the
catabolic pathways in
stage 2 with electron
transport and the synthesis
of ATP in stage 3.
THE CITRIC ACID CYCLE
The citric acid cycle (stage 3)
• operates under aerobic conditions.
• oxidizes the two-carbon acetyl group in acetyl CoA to CO2.
• produces reduced coenzymes NADH and FADH2.
• is named for the six-carbon citrate ion from citric acid
(C6H8O7), a tricarboxylic acid, formed in the first reaction.
• is also known as the tricarboxylic acid (TCA) cycle or the
Krebs cycle.
CITRIC ACID CYCLE OVERVIEW
In the citric acid cycle,
• six carbons move through the citric acid cycle,
producing oxaloacetate and 2CO2.
• each turn contains four oxidation reactions producing
the reduced coenzymes NADH and FADH2.
• one GTP (converted to ATP in the cell) is produced
during the citric acid cycle.
CITRIC ACID CYCLE OVERVIEW
• In the citric acid cycle, eight
reactions oxidize acetyl CoA
from pyruvate or fatty acids,
producing CO2 and the high-
energy compounds FADH2,
NADH, and GTP.
• Reactions involved in the citric
acid cycle include condensation,
dehydration, hydration,
oxidation, reduction, and
hydrolysis.
REACTIONS OF THE CITRIC ACID CYCLE
Step 1: Formation of citrate
Step 2: Formation of isocitrate
Step 3: Oxidation of isocitrate and formation of CO2
 Involves oxidation–reduction as well as decarboxylation

Step 4: Oxidation of α-ketoglutarate and formation of

CO2

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REACTIONS OF THE CITRIC ACID CYCLE
Step 5: Thioester bond cleavage in succinyl CoA and
phosphorylation of GDP
Step 6: Oxidation of succinate
Step 7: Hydration of fumarate
Step 8: Oxidation of L-Malate to regenerate
oxaloacetate

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REACTION 1: FORMATION OF CITRATE
In the first reaction of the citric acid cycle,
• citrate synthase catalyzes the condensation of an acetyl group (2C) from acetyl CoA
with oxaloacetate (4C) to yield citrate (6C) and coenzyme A.
• the energy to form citrate is provided by the hydrolysis of the high-energy thioester
bond in acetyl CoA.
REACTION 2: ISOMERIZATION
In reaction 2 of the citric acid cycle,
• citrate rearranges to isocitrate, a secondary alcohol.
• aconitase catalyzes the dehydration of citrate (tertiary alcohol) to yield cis-
aconitate, followed by a hydration that forms isocitrate (secondary alcohol).
REACTION 3: OXIDATION, DECARBOXYLATION [FORMATION OF CO 2
In reaction 3, isocitrate undergoes decarboxylation by isocitrate dehydrogenase.
• One carbon is removed by converting a carboxylate group (COO−) to CO2.
• The dehydrogenase removes hydrogen ions and electrons, used to reduce NAD+ to
NADH and H+.
REACTION 4: DECARBOXYLATION, OXIDATION OF
Α-KETOGLUTARATE & FORMATION OF CO2
In reaction 4, catalyzed by α-ketoglutarate dehydrogenase,
• α-ketoglutarate (5C) undergoes decarboxylation to yield (4C) succinyl CoA.
• oxidation of the thiol group (— SH) in HS — CoA provides hydrogen that is
transferred to NAD+ to form a second molecule of NADH and H+.
REACTION 5: HYDROLYSIS
In reaction 5, catalyzed by succinyl CoA synthetase,
• hydrolysis of the thioester bond in succinyl CoA yields succinate and HS — CoA.
• energy from hydrolysis is transferred to the condensation of phosphate and GDP
forming GTP, a high-energy compound similar to ATP.
REACTION 6: HYDROLYSIS
In reaction 6, catalyzed by succinate dehydrogenase,
• succinate is oxidized to fumarate, a compound with a
C = C bond.
• 2H lost from succinate are used to reduce the coenzyme FAD to FADH2.
REACTION 7: HYDRATION
In reaction 7, catalyzed by fumarase, water is added to the
double bond of fumarate to yield malate, a secondary alcohol.
REACTION 8: OXIDATION
In reaction 8, catalyzed by malate dehydrogenase,
• the hydroxyl group in malate is oxidized to a carbonyl group, yielding
oxaloacetate.
• oxidation provides hydrogen ions and electrons for the reduction of NAD+ to
NADH and H+.
SUMMARY, CITRIC ACID CYCLE
In the citric acid cycle,
• an acetyl group bonds with oxaloacetate to form citrate.
• two decarboxylations remove two carbons as two CO2.
• four oxidations provide hydrogen for three NADH and one FADH2.
• a direct phosphorylation forms GTP (ATP).
FIGURE 23.11 - THE CITRIC ACID CYCLE

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 Metabolic pathway by which glucose is converted to two molecules of
pyruvate (a C3 molecule)
Produces ATP and NADH-reduced coenzymes
Occurs in two stages - Six-carbon and three-carbon stages

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