carbohydrate metabolism- pyruvate decarboxylation

1. PYRUVATE
DECARBOXYLATION

2. • INTRODUCTION
• CELLULAR RESPIRATION
• LOCATION OF PYRUVATE DECARBOXYLATION
• ENZYMES INVOLVED
• PYRUVATE UTILIZATION PATHWAY
• REACTION MECHANISM
• DISORDERS
• CONCLUSION
CONTENTS

3. INTRODUCTION
• Pyruvate decarboxylation is a pivotal biochemical
process that occurs in the mitochondria of eukaryotic
cells as part of cellular respiration.
• This process bridges the glycolysis pathway, which
occurs in the cytoplasm, with the citric acid cycle
(Krebs cycle) that takes place within the
mitochondria.
• It is a fundamental process that links glycolysis to the
citric acid cycle, playing a crucial role in energy
production and cellular metabolism.

4. • Cellular respiration is the process by which cells
extract energy from nutrients, usually glucose, to
produce adenosine triphosphate (ATP), the
primary energy currency of cells.
• Cellular respiration consists of three main stages:
glycolysis, pyruvate decarboxylation, and the
citric acid cycle, followed by oxidative
phosphorylation.
CELLULAR RESPIRATION

5. FIG 1: CELLULAR RESPIRATION

6. ENZYMES INVOLVED
• Pyruvate decarboxylation is catalyzed by the enzyme pyruvate dehydrogenase
complex (PDC).
• PDC consists of three main enzymes: pyruvate dehydrogenase (E1),
dihydrolipoamide transacetylase (E2), and dihydrolipoamide dehydrogenase (E3).

7. PYRUVATE UTILIZATION PATHWAY
The TCA cycle-
• The Tricarboxylic Acid (TCA) Cycle, also known as the Citric Acid Cycle or Krebs Cycle, is a
central component of cellular respiration. It takes place in the mitochondria of eukaryotic
cells and plays a crucial role in the generation of energy through the oxidation of acetyl-CoA.

8. Here is an overview of the TCA cycle:
*Acetyl-CoA Entry:
•The TCA cycle begins with the entry of acetyl-CoA into the cycle.
•Acetyl-CoA is derived from the breakdown of glucose during glycolysis or from the oxidation of fatty acids.
*Formation of Citrate:
•Acetyl-CoA combines with oxaloacetate to form citrate, catalyzed by the enzyme citrate synthase.
•This step is a condensation reaction, releasing CoA.
*Isomerization and Decarboxylation:
•Citrate undergoes isomerization and a series of enzymatic reactions, resulting in the sequential removal of two
carboxyl groups as CO2.
•The decarboxylation steps occur in the form of isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate,
and malate.

9. *4. Energy Generation:
•The TCA cycle contributes to the production of high-energy molecules such as NADH and FADH2 through redox
reactions.
•For each turn of the cycle, three molecules of NADH, one molecule of FADH2, and one molecule of GTP (which
can be converted to ATP) are produced.
*5. Regulation:
•Enzymes within the TCA cycle are regulated to match the cell's energy demands.
•Key regulatory steps include the inhibition of isocitrate dehydrogenase and α-ketoglutarate dehydrogenase by
high levels of ATP and NADH.
*6. Connection to Electron Transport Chain (ETC):
•NADH and FADH2 generated in the TCA cycle carry high-energy electrons to the electron transport chain (ETC)
located in the inner mitochondrial membrane.
•The electrons flow through the ETC, leading to the pumping of protons across the inner mitochondrial membrane
and ultimately driving ATP synthesis.

10. *7. Oxaloacetate Regeneration:
•The TCA cycle ends with the regeneration of oxaloacetate, which can combine with a new molecule of
acetyl-CoA to initiate another cycle.
*8. Anaplerotic Reactions:
•Anaplerotic reactions replenish TCA cycle intermediates that are siphoned off for biosynthetic purposes.
•Examples include the conversion of pyruvate to oxaloacetate and the carboxylation of α-ketoglutarate to
form isocitrate.

11. The Glyoxylate Cycle:
The glyoxylate cycle is a modified version of the citric acid cycle that occurs in certain microorganisms, plants,
and bacteria. Unlike the standard citric acid cycle, the glyoxylate cycle allows for the net synthesis of
carbohydrates from acetyl-CoA, making it essential for organisms that use acetate or fatty acids as a carbon
source.
Here are the key features of the glyoxylate cycle:
1.Bypassing Decarboxylation Steps:
1. In the glyoxylate cycle, two decarboxylation steps present in the TCA cycle are bypassed.
2. Isocitrate lyase and malate synthase are the key enzymes that enable this bypass.
2.Formation of Succinate and Glyoxylate:
1. Glyoxylate is then combined with another acetyl-CoA molecule to form malate through the action of
malate synthase.
2. Isocitrate is cleaved into succinate and glyoxylate by the enzyme isocitrate lyase.

12. 3. Connection to Gluconeogenesis:
1. The glyoxylate cycle is closely linked to gluconeogenesis, the process of synthesizing glucose from non-
carbohydrate precursors.
2. The cycle produces intermediates (malate) that can be used in gluconeogenesis.
4. Examples of Organisms Utilizing the Glyoxylate Cycle:
1. Certain plants, bacteria (especially pathogenic bacteria like Mycobacterium tuberculosis), and fungi
employ the glyoxylate cycle.
5. In Mammals:
1. Mammals, including humans, do not possess a functional glyoxylate cycle. Instead, they rely on the TCA
cycle for energy production and anabolism.

13. REACTION MECHANISM
• Pyruvate, in the presence of PDC,
undergoes oxidative decarboxylation.
• A carbon atom is removed from pyruvate in
the form of carbon dioxide (CO2), resulting
in a two-carbon molecule—acetyl coenzyme
A (acetyl-CoA).
• Simultaneously, NAD+ is reduced to NADH.

14. DISORDERS
• Malfunctions in the pyruvate dehydrogenase complex can lead to disorders
such as pyruvate dehydrogenase deficiency,
• This affects energy metabolism and can manifest as neurological issues.

15. THANK YOU