Cellular Metabolism

Glycolysis

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The various pathways of
carbohydrate, fat, and protein
catabolism are finally run into the
common catabolic pathway, which
is made up of the citric acid cycle
and oxidative phosphorylation

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Carbohydrate Metabolism

• all carbohydrates are transformed into

glucose.
• Glucose is catabolized in three pathways
– Glycolysis
– Krebs cycle
– The electron transport chain and oxidative
phosphorylation

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Carbohydrate Metabolism

Glucose
Glycolysis

Oxygen No Oxygen
Pyruvic Acid
Aerobic Anaerobic

Krebs Cycle Fermentation

ETS

Before glucose can enter Krebs cycle it has to be “prepared” through

an anaerobic process in the process of glycolysis in cystosol.
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Carbohydrate Metabolism

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 Glycolysis
Phosphorylation

Isomerase

Phosphorylation

Cleaving
Dihydroxyacetonephoshphate
Oxidation & Phosphorylation

P-transfer The final products are:

– Two pyruvic acid molecules
Isomerase – Two NADH + H+ molecules
(reduced NAD+)
Dehydration
– A net gain of two ATP
molecules
P -Transfer
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 2,3-BPG is present in human red blood cells (RBC; erythrocyte) It interacts with deoxygenated
hemoglobin beta subunits by decreasing their affinity for oxygen, so it allosterically promotes the
release of the remaining oxygen molecules bound to the hemoglobin, thus enhancing the ability of
RBCs to release oxygen near tissues that need it most. 2,3-BPG is thus an allosteric effector.

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PEP has the highest-energy phosphate bond found (-61.9 kJ/mol) in living organisms,
and is involved in glycolysis and gluconeogenesis.
In plants, it is also involved in the biosynthesis of various aromatic compounds, and
in carbon fixation;
In bacteria, it is also used as the source of energy for the phosphotransferase system.

*) this particular reaction produce produce 1 ATP but also generates an excess energy as
heat that define a living cell.

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Control Points in Glycolysis

• Enzymes that control glycolysis

– Hexokinase
– Phosphofructokinase
– Pyruvate kinase

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PYRUVATE FATE

Alcohol
dehydrogenase

Lactate
dehydrogenase

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Anaerobic pathway
- This step regenerate NAD+ through
reaction catalyze by a dehydrogenase
(an enzyme linked to NADH) in the
Alcohol
absence of oxygen dehydrogenase

Pyruvate
Decarboxylase

Lactate
dehydrogenase

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Gluconeogenesis

• the pathway that is involved in

the synthesis of glucose.
• It operates mostly in the liver
and kidney.
• It uses 7 of the same enzymes as
glycolysis by running the
reactions in the opposite
direction from glycolysis
• It don’t have PFK, Hexokinase
and pyruvate kinase instead it
has 4 new enzyme;

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Gluconeogenesis

Pyruvate carboxylase catalyzes the

addition of a carboxyl group to pyruvate
to make oxaloacetate. The reaction
requires ATP

PEPCK catalyzes the conversion of

oxaloacetate to PEP and the reaction
requires GTP.

fructose-1,6bisphosphatase (F1,6BPase)
acts to remove a phosphate from F1,6BP,
yielding F6P.

glucose-6-phosphatase (G6Pase) which

acts to remove a phosphate from G6P to
yield free glucose

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Gluconeogenesis

Regulation of glycolysis and

gluconeogenesis is accomplished mainly
by the molecule fructose-2,6-
bisphosphate (F2,6BP).

It acts to stimulate glycolysis by turning

on PFK while at the same time acting to
inhibit gluconeogenesis by turning off
the corresponding enzyme, F1,6BPase.

Thus, when F2,6BP is present, glycolysis

is running and gluconeogenesis is
inhibited.
When F2,6BP is absent, gluconeogenesis
is running and glycolysis is inhibited.

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Cori Cycle
Glycolysis AND Pentose
Large glucose flux Phosphate
Pathway

Pentose
Phosphate
Pathway
Glycolysis

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Pentose Phosphate Pathway

• The pathway can begins anywhere depend on cell needs have

numerous starting and ending path.
• yields reducing agent (NADPH) that will be used in anabolic
reactions requiring electrons.
• Yield various C- chain sugar (mixing and matching it) resulting in;
• Ribose 5 phosphate (nucleotide) DNA, RNA
• Starting glycolysis pathway
• Various cofactors (CoA, FAD, NAD+/NADP+)
• Etc.

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Pentose Phosphate Pathway

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Pentose Phosphate Pathway

6C

6C

5C 5C
6C

5C 7C 3C

4C

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3C 6C 6C
 Oxidative stage of PPP

7C
5C 4C 5C

Non Oxidative stage

of PPP

5C

6C 3C
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NADPH FUNCTION

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TCA CYCLE – KREBS CYCLE – CITRIC ACID
CYCLE

• Is an AMPHIBOLIC reaction consist of both

anabolic/catabolic reaction.
• Is an Anaplerotic reactions which is a chemical
reactions that form intermediates of many other
metabolic pathways
• Occurs in the mitochondrial matrix

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KREBS CYCLE –
Anabolism

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KREBS CYCLE

• Pyruvic acid is converted to acetyl CoA in three main steps:

– Decarboxylation
• Carbon is removed from pyruvic acid
• Carbon dioxide is released
– Oxidation
• Hydrogen atoms are removed from pyruvic acid
• NAD+ is reduced to NADH + H+
– Formation of acetyl CoA
the resulting acetic acid is combined with coenzyme A, to form
acetyl CoA

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Pyruvate
Dehydrogenase

Figure2824.7
KREBS CYCLE

Malate Oxidation Isomerase

Dehydrogenase
Citrate Isocitrate
synthase dehydrogenase

hydration Oxidation
Fumarase
aconitase

Oxidation
Succinate
dehydrogenase Oxidation
a-ketoglutarate
CoA hydrolysis dehydrogenase
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Succinyl CoA synthetase
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Acetyl CoA is giving the energy to drive the reaction (an activated
intermediate substance). Thus this reaction is very favorable.

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The attachment of CoA is a high energy bond, thus the release of it produce GTP

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The double bond in fumarate is easily susceptible with water.

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The reaction of L malate – oxaloacetate in unfavorable, however the next rx. binding
of oxaloacetate with acetyl coA is highly favorable (coA has high energy) thus the
oxaloacetate amount will diminished faster, forcing the reaction to move forward.

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KREBS CYCLE

• An eight-step cycle in which each acetic acid is decarboxylated

and oxidized, generating:
– Three molecules of NADH + H+
– One molecule of FADH2
– Two molecules of CO2
– One molecule of ATP/GTP
• For each molecule of glucose entering glycolysis, two molecules
of acetyl CoA enter the Krebs cycle
• The Energy (ATP) will be produced when all the electrons
produced in citric acid cycle is dumped into the Electron
Transport System.

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KREBS CYCLE –
Control Point

The citric acid cycle is

regulated largely at the
level of availability of NAD+
and FAD.
When these are low in
abundance, the pathway
slows or stops at the places
where NAD+ or FAD are
needed.
High ATP condition also stop
the citric acid cycle. 38
KREBS CYCLE – Control Point

• There are 3 points of control within the cycle:

– Citrate synthase: inhibited by ATP, NADH, and succinyl
CoA; also product inhibition by citrate
– Isocitrate dehydrogenase: activated by ADP and NAD+,
inhibited by ATP and NADH
– -ketoglutarate dehydrogenase complex: inhibited by
ATP, NADH, and succinyl CoA; activated by ADP and NAD+

• There is one control point outside the cycle

– Pyruvate dehydrogenase: inhibited by ATP and NADH;
also product inhibition by acetyl-CoA
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KREBS CYCLE – GLYOXYLATE CYCLE

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KREBS CYCLE – GLYOXYLATE CYCLE

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Lipid Metabolism

• Started by breaking down of lipid in adipose cell, and

transporting fatty acid into blood stream by serum albumin
• Catabolism of fats involves two separate pathways
– Glycerol pathway
– Fatty acids pathway

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Lipid Metabolism

• Catabolism of fats
involves two
separate pathways
– Glycerol pathway
– Fatty acids pathway
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Lipid Metabolism

• Glycerol is converted to glyceraldehyde phosphate

– Glyceraldehyde is ultimately converted into acetyl CoA
– Acetyl CoA enters the Krebs cycle
• Fatty acids undergo beta oxidation which produces:
– Two-carbon acetic acid fragments, which enter the Krebs
cycle

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Mitochondria

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Lipid Metabolism - Oxidation

• -Oxidation: a series of reactions that cleaves carbon atoms

two at a time from the carboxyl end of a fatty acid (C2-C3)
• Fatty Acid with odd numbers of carbon atoms, produce
Propionyl-CoA, while fatty Acid with even numbers of carbon
atoms, produce Acetyl-CoA
• The complete cycle of one -oxidation requires four enzymes
– Reaction 1: Oxidation of the , carbon-carbon single
bond to a carbon-carbon double bond
– Reaction 2: Hydration of the carbon-carbon double bond
– Reaction 3: Oxidation of the -hydroxyl group to a
carbonyl group
– Reaction 4: Cleavage of the carbon chain
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Fatty Acid Metabolism - Efficiency

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Lipogenesis and Lipolysis

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Lipogenesis and Lipolysis

• Lipolysis, the breakdown of stored fat, is essentially

lipogenesis in reverse
• Glucose is easily converted into fat since acetyl CoA is:
– An intermediate in glucose catabolism
– The starting molecule for the synthesis of fatty acids
• Excess dietary glycerol and fatty acids undergo lipogenesis to
form triglycerides

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Ketone bodies

• Ketone bodies are produced from 2 acetyl CoA during

glycogen/glucose depleted condition (iex.
Fasting/diabetic/diet).
• It can not be converted into glucose but it will be delivered
throughout the cell to be used by other organ for energy via
citric acid cycle or for synthesis (iex. Heart, muscle and in
brain it will be the main sources of brain fatty acid).
• Some of the intermediate are unstable molecules  produce
acetone  ketosis.

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Protein Metabolism

if the carbon skeleton of an

amino acid is catabolized to
pyruvate,the body has two
possible choices:
(1) To use the pyruvate as
an energy supply via the
common catabolic pathway
(2) To use it as a building
block to synthesize glucose
(glucogenic) or yielding
ketone bodies (ketogenic).

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