This document summarizes key concepts relating to the tricarboxylic acid cycle, gluconeogenesis, and the metabolic fate of pyruvate. It discusses how pyruvate can be transformed into oxaloacetic acid or acetyl-CoA, and the role of these compounds in the TCA cycle and energy production. It also outlines the process of gluconeogenesis, including the major sites and key enzymes involved. Finally, it lists important substrates like lactate, glucogenic amino acids, and glycerol that can be used to synthesize glucose through gluconeogenesis.

1. Nursing - 6
Tricarboxylic acid cycle and
Gluconeogenesis

2. Metabolic fate of
pyruvate

4. * Pyruvate is transported to the mitochondria via
a special pyruvate transporter where it can be
transformed into: 1.oxaloacetic acid.(CO2
fixation):

5. * It provides extra 6 molecules of ATP formed by
oxidation of NADH by the ETC.

6. In animals:
The formation of acetyl CoA from pyruvate is a
key irreversible step in metabolism because
they are unable to convert acetyl CoA into
glucose.

7. Pyruvate as a junction point
 Pyruvate occupies an important junction between
various metabolic pathways. It may be
decarboxylated to acetyl-CoA which enters the
TCA cycle, or may be utilized for fatty acid
synthesis.
 Pyruvate may be carboxylated to oxaloacetate
which is used for gluconeogenesis.
 Pyruvate dehydrogenase step is the committed
step towards oxidation of glucose.

8. Citric acid cycle (CAC)
or Tricarboxylic Acid Cycle (TCA)
or Krebs Cycle
Definition:
It is a series of reactions in mitochondria, that
brings about the catabolism of acetyl residues,
liberating hydrogen equivalents which upon
oxidation, leads to the release of energy.

9. Functions of the Citric Acid Cycle
1. It is the final common oxidation pathway that
oxidizes acetyl CoA to CO2.
2. It is the source of reduced coenzymes that provide
the substrate for the respiratory chain.
3. It acts as a link between catabolic and anabolic
pathway (amphibolic role).
4. It provides precursors for synthesis of amino acids
and nucleotides.
5. Components of the cycle have direct or indirect
controlling effects on key enzymes of other
pathways.

11. Total ATP produced from complete oxidation of
one molecule of glucose during glycolysis,
oxidative decarboxylation and CAC :
Glycolysis G 2PA 8 ATP
Oxidative decarboxylation 2PA 2 acetyl CoA 6 ATP
(2 NADH + H+ ×3)
Oxidation of 2 acetyl CoA in CAC (12 ATP ×2) 24 ATP
38 ATP

12. Inhibitors of CAC:
1- Fluorocitrate inhibits aconitase.
2- Mercury and arsenite inhibit pyruvate and α–
ketoglutarate dehydrogenase complex.
3- Malonic acid inhibits succinic acid
dehydrogenase.

13. fluorocitrate
Inhibitors of CAC
Malonic acid
Arsenite and mercury

15. Definition:
Synthesis of glucose (and/or glycogen) from non-carbohydrate
precursors such as, lactate, glucogenic amino acids, glycerol and
propionate.
Some tissues such as the brain, RBCs, kidney medulla, lens and
cornea of the eyes, testis, and exercising muscle require a continuous
supply of glucose as a metabolic fuel. Liver glycogen can meet these
needs for only 10-18 hours in the absence of dietary intake of CHO.
During prolonged fasting, hepatic glycogen stores are depleted and
glucose is formed from, non- carbohydrate precursors.

16. Site:
The major site of gluconeogenesis is the liver (90%); it can also occur
in the cortex of the kidney (10%).
It occurs mainly in the cytoplasm and partly in the mitochondria.
Steps:
It is nearly the reversal of glycolysis except for the three irreversible
kinases as follows:-
Glycolytic key enzymes Gluconeogenic key enzymes
1- Glucokinase, hexokinase Glucose-6-phosphatase
2- Phosphofructo kinase-1 Fructose-1,6-bisphosphatase
3- Pyruvate Kinase Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase

17. Succinyl CoA

18. The gluconeogenic substrates give directly or indirectly
pyruvate, oxaloacetate or any intermediates of glycolysis
or C.A.C.
They include the following:
1. Lactate:
It diffuses out of active skeletal muscle or red cells, into the
blood and is carried to the liver, where it is converted to glucose
by gluconeogenic pathway .
* 6 high energy phosphate bonds are spent during synthesis of
glucose from 2 molecules of pyruvate:
2 ATP are utilized by pyruvate carboxylase.
2 GTP are utilized by PEP carboxykinase [2GTP= 2ATP]
2 ATP are utilized for reversal of phosphoglycerate kinase.

19. 2. Glucogenic amino acids:
They give pyruvate or oxaloacetate directly or
indirectly by giving intermediates of C.A.C as -
ketoglutarate, succinyl CoA, and fumarate. All a.a. can
give glucose except leucine (pure ketogenic).
After 18 hours fasting, proteins are considered as one
of the main sources of glucose.
3. Glycerol:
It is mobilized from adipose tissues. Two molecules
of glycerol are utilized for production of one molecule of
glucose in liver and kidney in fasting or low CHO diet.
Glycerol can not be utilized in adipose tissue which lacks
glycerol kinase.

21. Thanks