Glycolysis Krebs Cycle Benha 2024

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Faculty of Medicine,

Benha University.

Oxidative Decarboxylation
& Krebs cycle
Prof. Dr. Inas Abd Elmonem
Assistant prof. of Medical Biochemistry &
Molecular Biology
Learning outcomes
By the end of this lectures, the students will be able to:

– Clarify Oxidative decarboxylation of pyruvate.

– Define citric acid cycle(Krebs cycle), site and biomedical


importance.

– Calculate energy produced from complete oxidation of one


glucose molecule.
Glucose oxidation
Pathways for glucose oxidation are classified into:
I. Major pathways:
These pathways are grouped into three linked biochemical pathways (responsible for
ATP production).
A. Glycolysis: It is the first pathway which occur in the cytoplasm of
every cell in presence or absence of oxygen.
B. Pyruvate oxidation in the mitochondria.
C. Citric acid cycle in the mitochondria.
lI. Minor pathways: these pathways produce important compounds with no
energy production. They include:
A. Hexose monophosphate shunt (HMS) for production of pentoses and
NADPH+H.
B. Uronic acid pathway for production of uronic acid.
Glycolysis in red blood cells:
•Glycolysis in red blood cells occurs anaerobically (aerobic glycolysis
requires presence of mitochondria while RBCs lack of mitochondria).
•The end of glycolysis in RBCs is 2 molecules of lactate.
•It produces 2ATP only.

Products of glycolysis:
II- Oxidative decarboxylation of
pyruvate
•The 2 pyruvate molecules produced from glycolysis (under aerobic conditions) are
oxidized by pyruvate dehydrogenase enzyme complex (PDH) to form acetyl CoA.
•Pyruvate is transported at first to the inside of the mitochondria by special transporter.
•In the mitochondria, it is irreversibly converted to acetyl CoA by pyruvate
dehydrogenase complex (PDH).

• Oxidative decarboxylation of two pyruvate molecules produced from


glycolysis→2NADH

• Oxidation of one NADH → 2.5 ATP

• So, oxidation of 2NADH produces → 5 ATP


III- Citric acid cycle(Krebs cycle)
Definition: It is sequences of reactions by which
acetyl CoA is oxidized to CO2, water and energy.
The citric acid cycle is the final common pathway for
the oxidation of carbohydrate, lipid, and protein.
Site: All the steps of citric acid cycle occur in
mitochondria.
State: Under aerobic conditions (in the presence of
oxygen).
Steps: Citric acid cycle begins by condensation of acetyl CoA (2 carbons)
with oxaloacetate (4 carbons) to form citrate (6 carbons) which is reconverted
to oxaloacetate again by the end of the cycle.

Energy produced from oxidation of 2 molecules of acetyl CoA in citric acid cycle:

– Oxidation of one molecule acetyl CoA in citric acid cycle produces (10 ATP).

– So, two molecules of acetyl CoA which enter citric acid cycle produce (20 ATP).
Biomedical importance of citric acid cycle
TCA cycle is said to be amphibolic in nature i.e., has dual functions:
(I) Anabolic functions: The intermediates of the citric acid cycle are used
as precursors in the biosynthesis of many compounds:
– Synthesis of fatty acids from citrate.
– Synthesis of ketone bodies and cholesterol from acetyl CoA.
– Synthesis of glucose (gluconeogenesis).
– Synthesis of some non- essential amino acids:
• Pyruvate→ alanine
• Oxaloacetate→Aspartate
• α- ketoglutarate→Glutamate.
– Synthesis of heme from succinyl CoA and glycine amino acids.
Succinyl CoA +Glycine→→→ Heme.
(II) Catabolic functions:
Common pathway for oxidation of carbohydrates, fatty acids and proteins.
It is amphibol, which means that it is both
catabolic and anabolic
Energy produced from complete oxidation of one
glucose molecule:
1. Glycolysis: 5-7 ATP.
2. Oxidative decarboxylation of pyruvate (2 molecules of
pyruvate): 5 ATP
3. Oxidation of 2 acetyl CoA in the citric acid cycle: 20 ATP
So net energy produced from complete oxidation of glucose
= 30 to 32 ATP

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