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Lect 5 - Overview of Metabolism and Metabolic Regulation

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16 views21 pages

Lect 5 - Overview of Metabolism and Metabolic Regulation

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czdmvgbgfz
Copyright
© © All Rights Reserved
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BIOCHEMISTRY DEPARTMENT

Faculty of Medicine, UQU

Applied Biochemistry
2024 – 2025

Overview of metabolic
pathways, and mechanisms of
regulation

1 06/12/24
By the end of this lecture, students will be able to:

§ Discuss the medical significance of metabolism in the body


§ Describe the alternative terms of catabolism and anabolism
§ Illustrate the pathways and structures for metabolic reactions
§ Describe the biological significance of redox potential and
energy production in metabolic pathways.

2
Metabolism

Ø The sum of the chemical changes that convert


nutrients into energy and the chemically complex
products of cells
Ø Hundreds of enzyme reactions organized into
discrete pathways
Ø Substrates are transformed to products via many
specific intermediates Metabolic maps portray the
reactions

3 Dr. Hala Kamel 06/12/24


Metabolism

• The polymeric substances contained in the diet (proteins, carbohydrates,


and nucleic acids) cannot be used by the organism directly.
• Digestive processes first have to degrade them to monomers (amino acids,
sugars, nucleotides). These are then mostly broken down by catabolic
pathways into smaller fragments are then either used to obtain energy
through further catabolic conversion , or are built up again into more
complex molecules by anabolic pathways
• Catabolism: degradative pathways , usually energy-yielding!
( LYSIS )
• Anabolism: biosynthetic pathways, energy-requiring!
( GENESIS) 4

4 06/12/24
5 06/12/24
6 Dr. Hala Kamel 06/12/24
Catabolism & Anabolism

• Catabolic pathways converge to a


few end products
• Anabolic pathways diverge to
synthesize many biomolecules
• Some pathways serve both in
catabolism and anabolism
• Such pathways are amphibolic

7 Dr. Hala Kamel 06/12/24


Metabolism Proceeds in Discrete Steps

• Enzyme specificity
defines biosynthetic route
•Controls energy input
and output
•Allow for the
establishment of control
points.
•Allows for interaction
8
between pathways Dr. Hala Kamel 06/12/24
9

9 06/12/24
Central Themes of Metabolic Pathways

•Acetyl CoA is a common intermediate of all metabolic pathways.


It interconnects glucose, fatty acid and amino acid metabolism.
•Oxidation of dietary fuel leads to the capture of energy in the
form of ATP and NADH / FADH2.
•NADH / FADH2 transfer their electrons to O2 via the electron
transport chain. The energy released is used to synthesize ATP.
•ATP is the biochemical currency of energy . Several
thermodynamically unfavorable reactions are made possible by
the coupled hydrolysis of ATP.
• Biosynthesis involves the reduction of simple carbon compounds
to complex polymers. Most biosynthetic processes10make use of
NADPH as the electron donor.
• Biosynthetic and degradative pathways are distinct and
10 coordinately regulated 06/12/24
ATP
• ATP is the energy currency of cells
• catabolism produces ATP, which
drives activities of cells
• ATP cycle carries energy from
photosynthesis or catabolism to the
energy-requiring processes of cells

11

11 06/12/24
Mechanisms for ATP Formation

• Substrate Level Phosphorylation


• Oxidative Phosphorylation

NADH+H+ 3 ATP
FADH2 2 ATP

12

12 06/12/24
Redox in Metabolism

• NAD+ collects electrons released in catabolism


• Catabolism is oxidative - substrates lose reducing equivalents,
usually H- ions
• Anabolism is reductive - NADPH provides the reducing power
(electrons) for anabolic processes

13

13 06/12/24
Regulation of Metabolic Pathways

• Pathways are regulated to allow the organism to


respond to changing conditions.
• Most regulatory response occur in millisecond
time frames.
• Most metabolic pathways are irreversible under
physiological conditions.
• Regulation ensures unidirectional nature of
pathways.
• Flow of material thru a pathway is referred to as
flux.
• Flux is regulated by supply of substrates,
14

removal of products, and activity of enzymes

14 06/12/24
Regulation of metabolic
pathways

• Allosteric regulation: Enzymes that catalyze


irreversible steps are targets of feed-back inhibition or feed-
forward activation. Regulation is rapid but short-lived
• Covalent modification: Phosphorylation of enzymes
enables overall nutritional / metabolic status of the body to
regulate metabolic pathways at key regulatory steps. Low
concentration of triggering signals can have an amplified
effect. Regulation is transient by last long enough to affect ,the
next step in a regulatory cascade.
• Enzyme mass ( Induction) : Endocrine signals can
affect the transcription/translation of key regulatory
15 enzymes

15 06/12/24
• Energy charge/Reduction potential of the cell: Catabolism is
favored by a low energy charge and low NADH/NAD+ ratio.
• Compartmentation within the cell: catabolic substrates are kept
apart from enzymes by cellular compartments until a signal is
received
• Metabolic specialization of organs: In higher organisms,
specialized metabolic functions are performed by specific
tissues / organs. Eg: the liver monitors and maintains the blood
levels of key metabolites, the adipose tissue stores triglycerides.

16

16 06/12/24
Endocrine Regulation of Metabolism

• Metabolic processes are tightly regulated by the concerted actions of


hormones. Hormones regulate enzyme primarily by covalent
phosphorylation
• The three main endocrine signals that regulate metabolism are
epinephrine, glucagon and insulin.
• Epinephrine is responsible for the mobilization of glucose
(glycogenolysis) and an inhibition of enzyme activities of fuel storage
pathways.
• Glucagon also increases breakdown of glycogen, but in addition, it
promotes gluconeogenesis in the liver.
• Insulin opposes the functions of both glucagon and epinephrine. It
stimulates the uptake of glucose from the blood, stimulates glycogen and
FA biosynthesis and inhibits FA oxidation 17

17 06/12/24
Enzyme Regulation of Flux

Common mechanisms
• feedback inhibition – product of pathway down
regulates activity of early step in pathway

• Feed forward activation – metabolite produced early in


pathway activates down stream enzyme

18

18 06/12/24
Regulating Related Catabolic and Anabolic Pathways

• Anabolic & catabolic pathways involving the same


compounds are not the same
• Some steps may be common to both
• Others must be different - to ensure that each pathway
is spontaneous
• This also allows regulation mechanisms to turn one
pathway and the other off

19 Dr. Hala Kamel 06/12/24


References

• Text book of Biochemistry with Clinical Correlations Fifth Ed, Devlin TM Ed.
Wiley -Liss New York
• Lippincott's Reviews of Biochemistry, latest edition by Champe PC, Harvey RA,
Ferrier DR, Lippincott William & Wilkins London.
• Marks’ Basic Medical Biochemistry: A Clinical Approach, latest Edition By A.
D Marks, CM Smith and Lieberman M. Williams & Wilkins- London.
Thank you

21

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