Scribd
Upload
6 views

Lecture_Int and Reg of Metabolism_24

The document discusses the integration and regulation of metabolism, focusing on various metabolic pathways and the fate of different compounds like G-6-P, pyruvate, acetyl-CoA, tyrosine, and glycine. It outlines mechanisms of enzyme regulation, including changes in enzyme activity and the number of enzyme molecules, as well as specific regulatory mechanisms in glycolysis and gluconeogenesis. Additionally, it highlights the importance of feedback regulation and the role of isozymes in metabolic pathways.

Uploaded by

césar mpassi
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
6 views

Lecture_Int and Reg of Metabolism_24

The document discusses the integration and regulation of metabolism, focusing on various metabolic pathways and the fate of different compounds like G-6-P, pyruvate, acetyl-CoA, tyrosine, and glycine. It outlines mechanisms of enzyme regulation, including changes in enzyme activity and the number of enzyme molecules, as well as specific regulatory mechanisms in glycolysis and gluconeogenesis. Additionally, it highlights the importance of feedback regulation and the role of isozymes in metabolic pathways.

Uploaded by

césar mpassi
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 14

Заголовок

Цифровая 3D-медицина
Integration and Regulation of Metabolism
Результаты в области компьютерной графики и геометрического моделирования
Подзаголовок презентации
Dr. Svetlana V. Trofimova
2022
Common metabolic fate of different compounds
Examples of interactions among metabolic pathways
Metabolic alternatives
G-6-P can follow the following pathways: (1) glycolysis, (2) hydrolysis to become free
glucose, (3) incorporation into glycogen, and (4) to enter the pentose phosphate pathway.
Pyruvate can undergo: (1) decarboxylation to acetyl-CoA and all the metabolic possibilities
for this compound, (2) glucose or glycogen formation in the gluconeogenic pathway, (3)
transamination to give alanine, and (4) reduction to become lactate.
Acetyl-CoA follows: (1) oxidation in the citric acid cycle to produce energy, (2) fatty acid
synthesis, (3) cholesterol synthesis, (4) formation of ketone bodies, and (5) incorporation into
complex molecules (acetylation).
Tyrosine is used for the synthesis of: (1) proteins, (2) thyroid hormone, (3) catecholamines (dopamine, norepinephrine, epinephrine), (4) melanin, (5) phenols,
(6) oxidated to CO2 and H2O, with energy production, (7) used for glucose formation (gluconeogenesis), and (8) transformed to ketone bodies (ketogenesis).
Glycine can be used as substrate for the synthesis of: (1) proteins, (2) creatine, (3) glutathione, (4) heme, (5) purines; or can undergo (6) conjugation with bile
acids (glycocholic acid), (7) biotransformation reactions, such as the formation of hippuric acid from benzoic acid, (8) production of one-carbon moieties
(formyl) involved in numerous processes of synthesis, (9) conversion into serine, (10) formation of pyruvate, followed by all the pathways related to this
compound, and (11) transamination.
The activity of enzymes can be regulated by two mechanisms:

1. Modification of the activity of preexisting enzymes


a. One of the simplest mechanisms to modify an enzyme’s activity is the change in the amount of substrate in
the medium. When the substrate level is near or below the Km value of the enzyme, the reaction rate is directly
proportional to the substrate concentration.
b. Another mechanism consists of the regulation by metabolites, allosteric modifiers, modulators, or effectors.
These molecules bind to the enzyme and produce changes in substrate affinity. Positive regulators are those that
increase the enzyme’s affinity for its substrate and activity, while negative effectors reduce enzyme’s catalytic
function.
c. The activity of some enzymes can be covalently modified by the action of other enzymes, for example, the
addition of a phosphate group by kinases.
2. Increase or decrease in the number of enzyme molecules. The activity of an enzyme is directly
proportional to the amount of enzymes present. The number of enzyme molecules in the cell at a given time
depends on the balance between its synthesis and degradation.
a. Synthesis of protein. Regulation of enzyme synthesis is exerted mainly at the transcriptional level, by
regulating the production of messenger RNA coding for that enzyme from DNA. Another regulatory
mechanism takes place at the translational level, to control the conversion of the message contained in
mRNA into protein. Regulation of protein synthesis is slower than the mechanism that directly modifies
enzyme’s activity.
b. Protein degradation. The concentration of a given protein in the cell depends not only on the magnitude
of its synthesis, but also on its degradation. Enzymes are subjected to continual renewal, according to their
half-lives (time by which 50% of the enzyme is degraded), which ranges from minutes to days, and the
specific needs of the cell.
Regulatory mechanisms

 There are particular reactions in metabolic pathways which are considered limiting, since they
regulate the rate at which metabolites flow along the entire pathway.

 It is common that the first reaction and those at branching points in a metabolic pathway, as well as
the reactions that are markedly shifted from equilibrium, play a decisive regulatory role in the
pathway.

 The end product often exerts feedback actions on one or more “key” enzyme of the pathway to
control the magnitude of its own production.

 Isozymes with different catalytic properties, or subcellular localization, catalyze the same reaction
in different metabolic pathways, allowing independent regulation.
Regulation of Glycolysis and Gluconeogenesis

Glycolysis: glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 pyruvate


+ 2 NADH + 2 H+ + 2 ATP

Gluconeogenesis: 2 Pyruvate + 4 ATP + 2 GTP + 2 NADH +


2 H+ + 2 H2O → Glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+

Regulation is in two ways:


1. Kinetic properties of its hexokinase isoenzymes;
Hexokinase I, II, and III are blocked by glucose-6-phosphate.
Hexokinase IV (glucokinase) is not inhibited by glucose-6-
phosphate. This allows the conversion of excess glucose into
glucose 6 phosphate by the liver.
2. Allosteric regulation of the enzymes that catalyze the three
irreversible reactions:
hexokinase/glucose-6-phosphatase;
phosphofructokinase-1/fructose-1,6-biphosphatase;
pyruvate kinase/pyruvate carboxylase.
Regulation of Hexokinase and G6Pase in Glycolysis and Gluconeogenesis
Regulation of PFK-1 and F1,6BPase in Glycolysis and Gluconeogenesis
Hormonal Regulation of F2,6BP Production in Glycolysis and Gluconeogenesis
Regulation of Pyruvate Kinase & Pyruvate Carboxylase in Glycolysis and
Gluconeogenesis

You might also like