Overview of Metabolism

2CAFES – CU METABOLISM, BIOCHEMISTRY AND NUTRITION

Ana Isabel Padrão - [email protected]

14 de outubro de 2024

Faculty of Sport, University of Porto

2nd Cycle in Physical Activity, Exercise and Health

2024/2025
 Overview of Metabolism

Learning objectives:

 Understand the concept of metabolic pathways

Define the major types of metabolism: catabolism, anabolism, and amphibolic pathways

You should be able to discuss whether a given metabolic pathway is catabolic, anabolic, or amphibolic

Describe the relationship of macronutrients and micronutrients to metabolism

Describe the relationship of organs to metabolism and their specific functions as conferred by

special biochemical capabilities, including the role of isozymes

 Identify ATP as the energy current of cells

 Metabolism in the context of Biochemistry

 Amino acids and proteins

 Enzymes – function, and regulation

 Metabolism

Bioenergetics

Glucose homeostasis

Energy production in the citric acid cycle and electron transport chain

Amino acid metabolism

Fatty acid metabolism

 Metabolism pathways
Metabolism

 Living cells depend on

a complex, intricately
regulated system of
energy-producing and
energy-utilizing
chemical reactions
called metabolism

 These chemical
reactions are typically
catalyzed by enzymes
https://www.genome.jp/pathway/map01100
Metabolism can be viewed as…

 A series of chemical reactions

 A set of variable patterns that change due to

the energy and biosynthetic needs of the cell and

organism

http://www.quickmeme.com/meme/7jco
 Metabolism

 The chemical basis of life

 Metabolism provides us with

Energy

 Generation of energy from carbohydrates, protein, and fats

All of the molecules from which our bodies are constructed (YES, you really are what you eat!)

 Never stops

 Adapts to individual needs and the environment

 Has several metabolic pathways

 Metabolism – Sources of energy for the human body
Carbohydrates
 Food - fuel for the body Fates
Cannot be utilized Proteins
directly

 Digestion and absorption - break down of the

substance in food into simple, absorbable molecules

 Metabolism- enter metabolic reactions in the cell

= utilization of substances from food
Production of energy of living cells process
 Digestion and Absorption

 Digestion is the first stage of metabolism in which large

molecules are broken done into small molecules that can
be absorbed into the blood in the small intestine.
Most of these reactions are hydrolysis reactions
 Proteins are hydrolyzed into amino acids
 Polysaccharides are hydrolyzed into
monosaccharides
 Triglycerides are hydrolyzed into fatty acids and
glycerol.
Human body metabolism
 Biomedical Importance of Metabolism

Inherited genetic disorders

 Phenylketonuria –Inability to metabolize phenylalanine

Dis-regulation of normal metabolism

 Insulin insensitivity leading to type 2 diabetes

Adaption and metabolism

 Modulation of normal cellular metabolism to meet energy during rest and exercise

Mechanisms of pharmaceutical agents

 Inhibition of cyclooxygenase by ibuprofen to prevent prostaglandin synthesis and reduce inflammation

Toxicology
 Xenobiotic metabolism -metabolism of toxic compounds

Nutrition
 Macronutrient requirements for normal metabolic function and obesity

Cancer
 Modulation of normal cellular metabolism to meet the energy and macromolecule requirements of a tumor cell, e.g. the Warburg Effect
 Metabolism - Definitions

 Metabolism: the sum of all the chemical transformations taking place in a cell
“describe the interconversion of chemical compounds in the body, the pathways taken by individual
molecules, their interrelationships, and the mechanisms that regulate the flow of metabolites through the
pathways”
Metabolic pathways
 Consecutive steps that bring about specific, small chemical changes

 Usually the removal, transfer, or addition of a particular atom or functional group

 Metabolites = intermediates

 Substrates and products

 Intermediary metabolism = the combined activities of all the metabolic pathways

 Metabolism

 A highly coordinated cellular activity

 Many multi-enzyme systems (metabolic pathways) cooperate to accomplish four

functions:
1. Obtain energy by degrading energy-rich nutrients from the environment or stored
macromolecules

2. Convert nutrient molecules into precursors of macromolecules

3. Polymerize precursors into macromolecules

4. Synthesize and degrade biomolecules

 Bioenergetics

•Bioenergetics is the field of biochemistry concerned with the transformation and use of energy by living

cells.

•ENERGY

• Chemistry

• Thermal

• Nuclear

• Electric

• Mechanics

• Electromagnetic
 Laws of Thermodynamics
Apply to Living Organisms
 Living organisms cannot create energy from anything.
 Living organisms cannot destroy energy into anything.
 Living organisms may transform energy from one form to another.

In order to maintain organization within themselves, living systems must be able to extract useable
energy from their surroundings and release useless energy (heat) back to their surroundings.

Síntese celular Contração Impulso

Exemplos: de moléculas muscular nervoso
 Energy transformation in living cells

 Cells are continually rearranging molecules into new forms

 They do this for two reasons:

 to extract chemical bond energy and molecular building blocks from precursor molecules
they have scavenged from the environment

 to use the molecules and energy obtained to build, maintain and replicate their own

structures
 What we do with the food we eat
There are two main types of metabolism

•Catabolism

•the breakdown of chemical compounds into simpler forms

•Anabolism

•construction of more complex chemical compounds from simpler ones

 Metabolism
Catabolism vs. Anabolism

 Catabolism: The degradation and conversion of ingested food and stored fuel into energy

Anabolism: The biosynthesis of large molecules –requires energy

METABOLISM= Catabolism + Anabolism

 Metabolism
Catabolism vs. Anabolism
 Interplay between catabolism and metabolism and the central role of ATP

Metabolism is the sum of all chemical reactions in the cell

Four major energy-conserving intermediates link catabolism

and anabolism:

Uses Makes • ATP

ATP ATP
• NADH

• NADPH

• FADH2
 Energy Currency: Adenosine Triphosphate (ATP)

 A high-energy molecule composed of adenine, ribose and three phosphate molecules

 Only source of energy used directly by the cell

Energy is stored in the bonds that connect the phosphate groups

The body must continually produce ATP to provide a constant supply of energy
21

ATP-ADP cycle

 The free energy liberated in the hydrolysis of ATP is used to drive the endergonic reactions
 ATP is formed from ADP and Pi when fuel molecules are oxidized

 This ATP-ADP cycle is the fundamental mode of energy exchange in biological systems
 ATP is the energy currency of the cells
Energy Currency: ATP

 The energy from ATP drives all bodily functions, such as

contracting muscles, maintaining the electrical potential of nerve
cells, and absorbing food in the gastrointestinal tract.
 The metabolic reactions that produce ATP come from various
sources.
 Metabolism
Reaction of Oxidation-Reduction
Oxidation and Reduction – The role of coenzymes

Oxidation: Loss of hydrogen - Loss of electrons

Reduction: Gain of hydrogen - Gain of electrons

NAD+ and NADH

“NAD= Nicotinamide Adenine Dinucleotide”

From NADH to NAD+ (oxidation) “loss of hydrogen”

From NAD+ to NADH (reduction) “gain of hydrogen”
FAD and FADH2
“FAD= Flavin Adenine Dinucleotide”

Reaction of NAD+ to form NADH Reaction of FAD to form FADH2

Oxidation and reduction are present in metabolism

Energy-
compounds Energy-rich
Explanation: The
reduced
carbohydrates, fatty acids, Oxidation coenzymes
and amino acids were
oxidized, while the
reduced
enzymes NAD and FAD
were reduced =
Both oxidation and
reduction happen together
in metabolism
ETC

ETC – Electron transport chain

 Catabolism and Energy Production
An Example: Glycolysis

An example of a metabolic pathway (Glycolysis)

Metabolic pathways:
● A multi-step sequence of chemical reactions.
● A product of the first reaction becomes a substrate for the second
reaction.
● The energy released in the pathway is used to produce two types of
energy-rich molecules:
 Two molecules of ADP are phosphorylated to ATP.
 Two molecules of NAD+ are reduced to NADH/H+.

● Integrated (not separated) pathways

Metabolic pathways are

bidirectional.
Anabolism
Example: Biosynthesis of Glycogen

When glucose is not needed to meet energy needs, it can be

stored as the polysaccharide glycogen and used for future
energy needs
But wait!...There is a third type of metabolism
• Catabolism

• from the Greek: cata (down) + bolein (to throw)

• the breakdown of chemical compounds into simpler forms

• Anabolism

• from the Greek: an (up) + bolein (to throw)

• construction of more complex chemical compounds from simpler ones

•Amphibolic pathways

• Amphi= Dual, amphibolic: dual pathways (both catabolic and anabolic)

• Involve both anabolism and catabolism

• Citric acid cycle

 The citric acid cycle is Amphibolic

 An amphibolic pathway is both

catabolic and anabolic

• The production of citrate (6C) from

acetyl-CoA (2C) and oxaloacetate (4C) is

anabolic

• Steps 3 and 4 are catabolic because a

carbon is lost at each step

Santa Cruz Biotechnology (SCBT)
 Different pathways can intersect, forming an integrated and purposeful network of chemical reactions
Metabolic map (Metabolic pathways)

The metabolic map shows how all

pathways come together; it helps
us understand the effect of each
path on the entire metabolism
 The pathways involved in
catabolism and anabolism are
complex and extensive
 We will not learn the details of all
these pathways
We will study a few key pathways
extensively
And the most important molecule in all of metabolism is…?

Acetyl co-Enzyme A
Acetyl-CoA is the Common Product of Carbohydrate, Protein, and Fat Catabolism

Stored or
dietary sources
The Metabolic fate of Food
Your body´s metabolism
 Three Macronutrients

 Carbohydrate

 Fat

 Protein

 Micronutrients = everything else

 Vitamins

 Macrominerals

 Ca, P, Na, Cl, K, & Mg

 Microminerals
 Metabolism is regulated mostly by the control of metabolic enzymes and hormones

Isozymes

• Different proteins that catalyse the same chemical reaction, but may be differentially regulated, e.g. Hexokinase and
glucokinase
Phosphorylation (covalent modification)

Allosteric modification

• Fructose 2,6-bisphosphate

Hormonal regulation

Regulation can occur at different speeds

• Allosteric modification –Instantaneous

• Hormonal regulation via covalent modification of enzymes –Rapid

• Hormonal regulation via control of gene expression -Slow

 Isozymes Play an Important Role in the Regulation of Metabolism

Isozymes
are different molecular forms of the same enzyme (catalytic activity) that can have different kinetic and regulatory
properties

can be produced by different genes or alternative splicing

Because isozymes are different proteins, they can be differentially regulated by phosphorylation, allosteric mediators,

inhibitors, hormones, etc.

The expression of different isozymes provides differential regulation of metabolic pathways in various tissues and organs or

at different developmental stages

Isozymes you will encounter in this CU include:

Hexokinase (glucokinase)

Pyruvate kinase
Hormones Play an Important Role in the Regulation of Metabolism
 Metabolism

The 3D animation, “Metabolism in Motion”, is available

at https://vimeo.com/351043900 (accessed 2023-11-13).
 METABOLIC PATHWAYS MAY BE STUDIED AT DIFFERENT LEVELS OF
ORGANIZATION
Two Levels of organization:
1) Tissue and Organ level
2) Subcellular levels
Tissue and Organs Specialization
Organs Specialization – Metabolic Crosstalk

https://doi.org/10.1038/s41540-020-00159-1
Organs Specialization – Metabolic Crosstalk
Fifferent cells ≠ Energy forms

El Bacha, T., Luz, M. & Da Poian, A. (2010) Dynamic Adaptation of Nutrient Utilization in Humans. Nature
Education 3(9):8
 Metabolic pathways vary between cellular compartments, tissues, and
organs and work together for the benefit (or detriment) of the
organism as a whole

Transport and fate of major

carbohydrate and amino acid
substrates and metabolites. Note that
there is little free glucose in muscle,
since it is rapidly phosphorylated
following uptake.
 Metabolic pathways vary between cellular compartments, tissues, and organs and work together
for the benefit (or detriment) of the organism as a whole

Transport and fate of major lipid substrates and

metabolites. (LPL, lipoprotein lipase; MG,
monoacylglycerol; NEFA, nonesterified fatty
acids; TG, triacylglycerol; VLDL, very low density
lipoprotein.)
Metabolic Profile of several organs
 Liver

Is the most metabolically active organ in the body

First organ to metabolize, store, and distribute nutrients after
absorption
Proteins, carbohydrates, and fats are absorbed as:
Amino acids
Monosaccharides
Glycerol and fatty acids
 Proteins, carbohydrates, and fats are in the liver converted to
 Usable forms of energy
 Storage forms
• Glycogen
• Triglycerides
 Liver

Major Service for the other organ and tissues

Function
Major Does almost everything -gluconeogenesis; ß-oxidation; ketogenesis; synthesis of proteins (e.g., albumin,
lipoprotein, clotting factors, etc.), NH3 detoxification as urea, purine degradation to uric acid, cholesterol
Pathways

Major Free fatty acids, glucose (well fed),

lactate, glycerol, fructose, amino acids
substrates
Major Glucose, VLDL (triacylglycerol), HDL,
ketone bodies, urea, uric acid, bile acids,
Products proteins
Specialist Glucokinase, glucose-6-phosphatase,
glycerol kinase, PEP carboxykinase,
Enzymes fructokinase, arginase
 Adipose Tissue

Major Storage and breakdown of triacylglycerol

Function
Major Esterification of fatty acids and lipolysis;
lipogenesis
Pathways
Major Glucose, lipoprotein, triacylglycerol
substrates
Major Free fatty acids, glycerol
Lipoprotein lipase,
Products
Specialist Lipoprotein lipase,
hormone-sensitive lipase
Enzymes
 Muscle

Major Rapid movement. Sustained movement.

Function
Major Glycolysis
Aerobic pathways,
Pathways e.g., ß-oxidation and citric acid cycle
Major Glucose
Ketone bodies, triacylglycerol in VLDL
substrates and chylomicrons, free fatty acids
Major Lactate and amino acids
Products
Specialist Lipoprotein lipase
Respiratory chain well developed
Enzymes
 Erythrocytes

Major Transport of O2
Function
Major Glycolysis, pentose phosphate pathway.
No mitochondria and therefore no ß-
Pathways oxidation or citric acid cycle.
Major Glucose
substrates
Major Lactate
Products
Specialist (Hemoglobin)
Enzymes
Metabolic Integration

• Fígado: processamento e distribuição e de nutrientes

• Tecido adiposo: armazenamento e o fornecimento de ácidos

gordos e glicerol

• Músculos: a utilização de ATP pelos músculos para o

desenvolvimento de atividade mecânica

• Cérebro: utilização de energia pelo cérebro para a

transmissão de impulsos elétrico

• Sangue/eritrócitos: transporte de oxigênio, metabólitos e

hormônios pela corrente sanguínea.

• Pâncreas: Regulação Hormonal

 Metabolism in the Cell

Chemical reactions involved in energy production

Different cells perform different functions

Each cell’s structure in similar

Metabolism Takes Place within Cells
 Cell Structure

Cell construction is similar for all cells

Outside of cell
Plasma membrane
Holds in the cell contents

Inside of cell
Includes several special internal structures: organelles
 Internal Cell Structure

Organelles
Mitochondrion
“Powerhouse of the cell”
Aerobic metabolism
Ribosomes
Help manufacture proteins
Smooth endoplasmic reticulum
Produces lipids
Cytosol
Fluid portion of the cell
Anaerobic metabolism
 Metabolic pathways occur at specific sites in cells
Protein synthesis

Triacylglycerol
synthesis

Intracellular location and

The central
overview of major metabolic
pathways in a liver parenchymal
role of
cell. (AA →, metabolism of one or mitochondria
more essential amino acids; AA
, metabolism of one or more
nonessential amino acids.)
 Quick Review

Metabolism is the sum of all metabolic processes that occur in the cells

• Metabolic processes follow specific pathways

• Anabolic which uses energy to build new substances

• Catabolic which produces energy by breaking down molecules

 The products of digestion provide the tissues with the building blocks for the biosynthesis of complex molecules and also with the fuel
for metabolic processes.
 Nearly all products of digestion of carbohydrates, fat, and protein are metabolized to a common metabolite, acetyl-CoA, before
oxidation to CO2 in the citric acid cycle.
 Pathways are compartmentalized within the cell. Glycolysis, glycogenesis, glycogenolysis, the pentose phosphate pathway, and
lipogenesis occur in the cytosol. The mitochondria contain the enzymes of the citric acid cycle and for β-oxidation of fatty acids, as well
as the respiratory chain and ATP synthase. The membranes of the endoplasmic reticulum contain the enzymes for a number of other
processes, including triacylglycerol synthesis and drug metabolism.
Mitochondria is the site of most of the metabolic reactions

Metabolic pathways are regulated by rapid mechanisms affecting the activity of existing enzymes, that is, allosteric and covalent
modification (often in response to hormone action) and slow mechanisms that affect the synthesis of enzymes.
 Active Learning

1. Qual o papel do catabolismo na perda de peso?

1. Qual o papel do anabolismo no bodybuilding?

 Question 1

Which term most precisely describes the cellular process of breaking down large molecules into
smaller ones?

1) Catabolism (catabolic pathways)

2) Metabolism

3) Anabolism (anabolic pathways)

4) Phosphorylation

5) Dehydration
 Question 1

Which term most precisely describes the cellular process of breaking down large molecules into
smaller ones?

1) Catabolism (catabolic pathways)

2) Metabolism

3) Anabolism (anabolic pathways)

4) Phosphorylation

5) Dehydration
 Question 2

Which of the following is (are) true for anabolic pathways?

1) They do not depend on enzymes

2) They are usually spontaneous chemical reactions

3) They consume energy to build up protein from amino acids

4) They release energy as they degrade protein to amino acids

5) They release energy and breakdown of glucose

 Question 2

1. Which of the following is (are) true for anabolic pathways?

1) They do not depend on enzymes

2) They are usually spontaneous chemical reactions

3) They consume energy to build up protein from amino acids

4) They release energy as they degrade protein to amino acids

5) They release energy and breakdown of glucose

 To Think…  Ratos Wistar foram submetidos a dietas compostas

exclusivamente de carboidratos (Grupo 1), ou lípidos (Grupo 2)

Diet ou proteínas (Grupo 3). Estes três tipos de macronutrientes são

essenciais para a sobrevivência. Não havendo outras restrições na

Group 1. Carbohydrates
dieta, prever que grupo de animais sobreviveria:
Group 2. Lipids
1. Grupo 1

Wistar Group 3. Proteins 2. Grupo 2

Rats
3. Grupo 3

4. Nenhum Grupo

5. Todos os grupos