Chem 1223

Lucas, Ramil S.
KREBS CYCLE / TCA

1. Indicate whether the pathway is anabolic or catabolic.
 Krebs cycle is both anabolic and catabolic pathway, which means it is amphibol.
2. Importance of the pathway.

 Tricarboxylic acid cycle/ the citric acid cycle, or Krebs cycle is important for aerobic respiration
and one of the main source of energy in the cells. Where the aerobic respiration is a reaction that
transfers energy into the cells. The Krebs cycle is what causes electron carriers to form, and lastly
Krebs cycle occurs inside the mitochondria which serves as the power house of the cell.
3. What is the starting molecule for the pathway?

 The starting molecule for Krebs cycle is Acetyl-CoA which is combined with Oxaloacetate, but
before entering the Krebs cycle the pyruvate entered the mitochondria where Krebs cycle happens
and then reacted with CoA to produce acetyl-CoA.
4. Enumerate the reaction steps in each pathway and give the ff:
a. General reaction for each step (example: Isomerization reaction)
 Step 1: Condensation reaction of Acetyl-CoA and Oxaloacetate to form Citrate
 Step 2: Isomerization reaction of Citrate to Isocitrate
 Step 3: Oxidation reaction of Isocitrate to α-ketoglutarate
 Step 4: Oxidation reaction of α-ketoglutarate to Succinyl CoA
 Step 5: Conversion of Succinyl CoA to Succinate
 Step 6: Oxidation reaction of Succinate to Fumarate
 Step 7: Conversion of Fumarate to Malate
 Step 8: Conversion of Malate to Oxaloacetate
b. Enzymes involved and the enzyme classification.

 Step 1: Citrate Synthase (EC 2.3.3.1) – an enzyme involved in catalyzing the combination of the
Acetyl-Coa and Oxaloacetate to Citrate and CoA are formed after the thioester bond is
hydrolyzed. The citrate synthase has a molecular weight of 52 kDa.
 Step 2: Aconitase (EC 4.2.1.3) – is an enzyme involved in catalyzing the reversible isomerization
of citrate to isocitrate, and has a molecular weight of 82.7 kDa.
 Step 3: Isocitrate Dehydrogenase (EC 1.1.1.42) – is an enzyme involved in catalyzing the
oxidative decarboxylation of isocitrate to α-ketoglutarate, and has a molecular weight of 42 kDa.
 Step 4: α-ketoglutarate Dehydrogenase (EC 1.2.4.2) – an enzyme involved in catalyzing the
conversion of α-ketoglutarate to Succinyl CoA, and has a molecular weight of 70 kDa.
 Step 5: Succinyl CoA Synthetase (EC 6.2.1.5) - in the absence of oxygen, an enzyme capable of
producing ATP through substrate-level phosphorylation, and converting succinyl CoA to
succinate. The succinyl CoA synthethase has a molecular weight of 140 kDa.
 Step 6: Succinate Dehydrogenase (EC 1.3.5.1) – an enzyme catalyzes the oxidation of succinate
into fumarate. Succinate dehydrogenase is a heterotetramer composed of flavoprotein with a
molecular weight of about 70 kDa, iron-sulfur protein with a molecular weight of about 30 kDa,
and two hydrophobic anchoring subunits with a molecular weight of 7-17 kDa.
 Step 7: Fumarase (EC 4.2.1.2) - an enzyme that catalyzes the reverse conversion of fumarase to
malate, and has a molecular weight of 49 kDa.
 Step 8: Malate Dehydrogenase (EC 1.1.1.37) – an enzyme that catalyzes the interconversion
between matae and oxaloacetate, and a key protein for central oxidative pathway. This enzyme
has a molecular weight of 35 kDa.
5. Which reaction step is the key regulatory step? or indicate key control and regulation for the
pathway.
 There are three control steps in Krebs cycle first is Step 1: citrate synthase reaction's substrates,
acetyl-CoA and oxaloacetate, are perhaps the most important regulators. The rate of reaction is
regulated by the levels of acetyl-CoA and oxaloacetate in the mitochondria, which are controlled
by substrate supply. Lastly, the citrate synthase was inhibited by succinyl CoA, citrate, ATP and
NADH. The second control step is Step 3 where isocitrate dehydrogenase is being used, where it
is allosterically stimulated by ADP that supplemented the enzymes affinity for substrates. The last
control step is Step 4 where α-ketoglutarate Dehydrogenase is involved, this enzyme is inhibited
by reactive oxygen species, and high energy charges.
6. What is the net reaction equation for the pathway?
7. What is the product molecule of the pathway? Indicate other pathways that the product/s can
enter into. This shows a link of the pathway to other metabolic pathways.
 There are a total of 2 carbon dioxides and hydrogen ions, 1 CoA/GTP/FADH2, and 3 NADH
products after the Krebs cycle. The products of Krebs cycle will enter the electron transport chain
and oxidative phosphorylation.
PENTOSE PHOSPHATE PATHWAY
1. Indicate whether the pathway is anabolic or catabolic
 The PPP is parallel to glycolysis but PPP’s role is more preferred as anabolic than catabolic.
2. Importance of the pathway.

 This pathway is very important because it provides Nicotinamide Adenosine Dinucleotide
Phosphate Hydrogen (NADPH) which is extremely important reducing agent for different
detoxification processes, and for different biosynthesis (ex. Nucleotide, fatty acid, cholesterol,
etc.). Also this pathway provides a way to break down pentose sugars we ingested. Lastly this
pathway is responsible for the synthesis of ribose for RNA, ATP, ADP, AMP, NADH, coenzyme
A, FAD and deoxyribose for DNA. This pathway takes place in the cytosol of the cell of the liver,
mammary glands, and gonads tissues
3. What is the starting molecule for the pathway?

 The starting molecule of the pentose phosphate pathway is glucose 6-phosphate
4. Enumerate the reaction steps in each pathway and give the ff:
a. General reaction for each step (example: Isomerization reaction)
Oxidative Phase
 Step 1: Dehydrogenation of Glucose 6-phosphate to 6-phosphoglucono-δ-lactone

 Step 2: Hydrolysis reaction of 6-phosphoglucono-δ-lactone to 6-phosphogluconate
 Step 3: Decarboxylation reaction of 6-phosphogluconate to ribulose 5-phosphate
 Step 4: Isomerization reaction of ribulose 5-phosphate to D-ribose 5-phosphate
Non-oxidative Phase
 Step 5 / First reaction: (a) Isomerization reaction of D-ribose 5-phosphate to ribulose 5-phosphate,
and (b) Epimerization reaction of ribulose 5-phosphate to xylulose 5-phosphate
 Step 6 / Second reaction: Conversion reaction of xylulose 5-phosphate with another D-ribose 5-
phosphate to form seduheptulose 7-phosphate and glyceraldehyde 3-phosphate (GA3P)
 Step 7 / Third reaction: Conversion reaction of seduheptulose 7-phosphate with GA3P to form
erythrose 4-phosphate and fructose 6-phosphate
 Step 8 / Fourth Reaction: Conversion reaction of erythrose 4-phosphate with xylulose 5-
phosphate to form fructose 6-phosphate and GA3P
b. Enzymes involved and the enzyme classification.

 Step 1: Glucose 6-phosphate dehydrogenase (EC 1.1.1.49) – an enzyme that catalyzes the transfer
of hydride ion from glucose 6-phosphate into the NADP+ that resulted NADPH and 6-
phosphoglucono-δ-lactone. This enzyme has a molecular weight of 194 kDa.
 Step 2: Lactonase (EC 3.1.1.25) – an enzyme that catalyzes the transformation of 6-
phosphoglucono-δ-lactone onto 6-phosphogluconate. This enzyme has a molecular weight of 43
kDa.
 Step 3: 6-phosphogluconate dehydrogenase (EC 1.1.1.44) – an enzyme that catalyzes the
oxidative decarboxylation of 6-phosphogluconate to form ribulose 5-phosphate and a carbon
dioxide molecule, also this enzyme catalyzes the oxidation of 6-phosphogluconate and the
electron was picked up by the NADP+ to form another NADPH. This enzyme has a molecular
weight of 51 kDa.
 Step 4 & 5a: Phosphopentose isomerase (EC 5.3.1.6) – an enzyme that catalyzes the reversible
isomerization of ribulose 5-phosphate a ketose into D-ribose 5-phosphate which is an aldose This
enzyme has a molecular weight of 244 kDa.
 Step 5b: Phosphopentose epimerase (EC 5.1.3.1) – an enzyme that catalyzes the epimerization or
changing the stereochemistry of of ribulose 5-phosphate to xylulose 5-phosphate. This enzyme
has a molecular weight of 74 kDa.
 Step 6, 7 & 8: Transketolase (EC 2.2.1.1) – In step 6 this enzyme needs the help of a cofactor
called thiamine pyrophosphate then catalyzes the reaction of xylulose 5-phosphate and D-ribose
5-phosphate where the 2-hydroxyacetaldehyde from xylulose 5-phosphate is transferred onto D-
ribose 5-phosphate, to form seduheptulose 7-phosphate and glyceraldehyde 3-phosphate (GA3P).
In step 7 it catalyzes the transfer of 1,3-dihydroxypropan-2-one from seduheptulose 7-phosphate
onto GA3P to form erythrose 4-phosphate and fructose 6-phosphate (where fructose 6-phosphate
is an glycolytic intermediate, as well as GA3P). Lastly in step 8 this enzyme catalyzes the transfer
of 2-hydroxyacetaldehyde from xylulose 5-phosphate leftovers onto erythrose 4-phosphate to
form fructose 6-phosphate and GA3P. This enzyme has a molecular weight of 68 kDa.
5. Which reaction step is the key regulatory step? or indicate key control and regulation for the
pathway.
 The step 1 is a key regulatory step were it uses Glucose 6-phosphate dehydrogenase as an enzyme
also called rate-controlling enzyme of the PPP. Where it was inhibited by NADPH and the
NADP+ allosterically stimulated the enzyme.to increase the flux of glucose 6-phosphate.
6. What is the net reaction equation for the pathway?

 Oxidative Phase
 Non-oxidative Phase
7. What is the product molecule of the pathway? Indicate other pathways that the product/s can
enter into. This shows a link of the pathway to other metabolic pathways.
 The main product of the pentose phosphate pathways are the following (1) D-ribose 5-phosphate
where it can be used to synthesized ribose for RNA, ATP, ADP, AMP, NADH, coenzyme A,
FAD and deoxyribose for DNA. This product can enter the non-oxidative phase of the PPP where
it can be converted into molecules like fructose 6-phosphate, GA3P, and glucose 6-phosphate that
can enter glycolysis. (2) The GA3P and Fructose 6-phosphate from non-oxidative phase will enter
the glycolysis and then produces pyruvate that can used for gluconeogenesis.

Chem 1223

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Lucas, Ramil S.

KREBS CYCLE / TCA

2. Importance of the pathway.

3. What is the starting molecule for the pathway?

b. Enzymes involved and the enzyme classification.

6. What is the net reaction equation for the pathway?

2. Importance of the pathway.

3. What is the starting molecule for the pathway?

 Step 1: Dehydrogenation of Glucose 6-phosphate to 6-phosphoglucono-δ-lactone

b. Enzymes involved and the enzyme classification.

6. What is the net reaction equation for the pathway?

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