This document summarizes key aspects of metabolic pathways involving glucose-6-phosphate, pyruvate, acetyl CoA, and the tricarboxylic acid (TCA) cycle. It discusses the fates and oxidation of glucose-6-phosphate, pyruvate, and acetyl CoA through glycolysis, gluconeogenesis, glycogenolysis, the HMP shunt, the Cori cycle, and the TCA cycle. It also describes the enzymes, regulation, energetics, anabolic and amphibolic roles of the TCA cycle. The complete oxidation of one glucose molecule through these pathways produces a total of 32 ATP molecules.
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This presentation discusses basic details about Krebs cycle( Tricarboxylic acid cycle or Citric acid cycle), It also discusses the overall energy production in the process also including its connection to glycolysis and other biochemical processes. As Krebs cycle acts as the central biochemical cycle that connects all other metabolic reactions.
Gluconeogenesis: Defined as biosynthesis of glucose from non-carbohydrate precursors
-Gluconeogenesis: an intro
-Thermodynamic Barriers (Each barrier detail explanation)
- Energetics of gluconeogenesis
-Substrates of gluconeogenesis (each substrate and pathway explained)
-Regulation of Gluconeogenesis, hormonal and transcriptional regulation
These are major source of energy for living organisms.
Supplying a huge array of metabolic intermediates for biosynthetic reactions.
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Gluconeogenesis: Defined as biosynthesis of glucose from non-carbohydrate precursors
-Gluconeogenesis: an intro
-Thermodynamic Barriers (Each barrier detail explanation)
- Energetics of gluconeogenesis
-Substrates of gluconeogenesis (each substrate and pathway explained)
-Regulation of Gluconeogenesis, hormonal and transcriptional regulation
These are major source of energy for living organisms.
Supplying a huge array of metabolic intermediates for biosynthetic reactions.
The structural elements in cell coat or connective tissues.
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2. TCA cycle and fate of pyruvate & acetyl CoA.pptx
1. Metabolic fate of
Glu-6-P, Pyruvate & Acetyl CoA.
TCA cycle/ Krebs cycle / Citric acid cycle
Dr. Santhosh Kumar N
Associate Professor of Biochemistry
“Believe yourself ”
Have a great day to all
7. • The citric acid cycle is the central metabolic hub of the cell.
• It is the gateway to the aerobic metabolism of any molecule that can be
transformed into an acetyl group or dicarboxylic acid.
• The aerobic processing of glucose starts with the complete oxidation to CO2.
• This oxidation takes place in the citric acid cycle, a series of reactions known as
the “tricarboxylic acid (TCA) cycle” or the “Krebs cycle”.
8. TCA cycle is the final common pathway for the oxidation
of fuel molecules – amino acids, carbohydrates & fatty
acids that enter the cycle as acetyl CoA
The enzymes of citric acid cycle are located in the
mitochondrial matrix.
10. Energetics of TCA cycle
Isocitrate dehydrogenase (NADH+H+ =2.5ATPs) +2.5 ATP
α-Ketoglutarate Dehydrogenase (NADH+H+) + 2.5ATP
Succinyl Thiokinase [1GTP = 1ATP)] + 1 ATPs
Succinate Dehydrogenase [FADH2 = 1.5 ATP)] + 1.5 ATPs
Malate Dehydrogenase (NADH+H+) +2.5 ATP
one molecule of acetyl CoA produced no. of ATPs in TCA cycle 10 ATPs
11. Regulation of TCA cycle
• α-ketoglutarate dehydrogenase is inhibited by NADH, Succinyl-CoA and
Arsenate.
• Aconitase enzyme is inhibited by fluoro acetate
• The key enzymes of the TCA cycle are also regulated allosterically by Ca2+, ATP
and ADP.
12. Significance of the TCA Cycle
• Final common oxidative pathway and integration of major metabolic
pathways
• It is the source of reduced coenzymes that provide the substrate for the
respiratory chain
• Provides the precursors for the building blocks of many molecules such as
amino acids, Nucleotide bases (Purines & Pyrimidines) and Porphyrin
• It act as a link b/w catabolic & anabolic pathways (amphibolic role)
13. Anabolic role of TCA cycle
It provides the intermediates for the synthesis of many compounds
14. Anaplerotic reaction of TCA cycle
• filling up reactions which supply intermediates of TCA cycle .
1
2
3
4
5
6
17. Pathways Total ATPs
A. Glycolysis 7 ATPs
B. Oxidative decarboxylation of 2 pyruvate to 2 Acetyl CoA [2 x NADH] 5 ATPs
C. TCA cycle (2 moles of acetyl CoA involved 2x10) 20ATPs
one molecule of glucose produced total ATPs 32 ATPs
Energetics on complete oxidation of glucose:
18. Acetyl CoA
Synthesis of
Cholesterol
Acetylation reactions
(Detoxification)
Synthesis of Melatonin
Formation of Acetylcholine
Formation of
Ketone Bodies
Oxidation of TCA cycle
Denovo synthesis of FA
HMG -CoA
PYRUVATE
Acetylation of amino- sugars ,
glycoprotein
Ketogenic
a.a’s
β-Oxidation
of FA
Cytoplasmic
Synthase &
Reductase
Mitochondrial
Synthase &
lyase
Fate of Acetyl CoA
The PDH complex is comprises of multiple copies of 3 separate enzymes & coenzymes.
Pyruvate dehydrogenase (PDH)
Dihydrolipoamide S-acetyltransferase (DLAT)
Dihydrolipoamide dehydrogenase (DLD).
The complex also requires 5 different coenzymes: CoA, NAD+, FAD+, thiamine pyrophosphate (TPP) and lipoic acid
Reactions of the TCA Cycle
Condensation of Acetyl-CoA with oxaloacetate to form citrate by citrate synthase.
Citrate is isomerized to isocitrate by the enzyme aconitase. The reaction occurs in two steps, dehydration to cis-aconitate & rehydration to isocitrate.
Isocitrate is dehydration to oxalosuccinate initially, then decarboxylation to give α-ketoglutarate by isocitrate dehydrogenase
Alpha-ketoglutarate (α-KG) is oxidative decarboxylated to Succinyl -CoA by the α-ketoglutarate dehydrogenase& it generates NADH [equal to 2.5ATPs].
The Succinyl-CoA is converted to succinate by Succinyl-CoA thiokinase. This reaction produces GTP [equal to 1ATP].
Succinate dehydrogenase catalyzes the oxidation of succinate to form fumarate and it generates FADH2 [equal to 1.5 ATPs].
The fumarase catalyzed by the addition of water to fumarate to gives malate.
The final enzyme, forwards the reaction of the TCA cycle, the oxidation of malate to oxaloacetate (OAA) by malate dehydrogenase, and this reaction produces NADH [equal to 2.5ATPs].
Finally oxaloacetate is regenerated, thus two carbon atoms form acetyl-coA enter the cycle.
The reactions concerned to replenish or fill up the intermediates of citric acid cycle are called anapleurotic reactions
Pyruvate carboxylase catalyses conversion of pyruvate to oxaloacetate
Pyruvate is converted to malate by NADP+ dependent Malate dehydrogenase (Malic enzyme)
Alpha ketoglutarate is also synthesized from glutamate by glutamate dehydrogenase
Amphibolic nature of the TCA cycle is both catabolic and anabolic in nature
Oxaloacetate is precursor for aspartate
Alpha ketoglutarate can be transaminated to glutamate
Succinyl CoA is used for synthesis of heme
Citrate (mitochondrial) is transported to cytoplasm and provides substrate for fatty acid synthesis