Integrative Human Biochemistry

Andrea T. Da Poian

Miguel A. R. B. Castanho 

Integrative

Human

Biochemistry

A Textbook for Medical Biochemistry

Integrative Human Biochemistry

Andrea T. Da Poian • Miguel A. R. B. Castanho

Integrative Human

Biochemistry

A Textbook for Medical Biochemistry

ISBN 978-1-4939-3057-9 ISBN 978-1-4939-3058-6 (eBook)

DOI 10.1007/978-1-4939-3058-6

Library of Congress Control Number: 2015946870

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Andrea T. Da Poian

Instituto de Bioquímica Médica

Leopoldo de Meis

Federal University of Rio de Janeiro

Rio de Janeiro , Rio de Janeiro , Brazil

Miguel A. R. B. Castanho

Institute of Biochemistry and

Institute of Molecular Medicine

School of Medicine

University of Lisbon

Lisbon , Portugal

This book is a tribute to the legacy

of Leopoldo de Meis for his inspiration

to younger generations. Thanks, Leopoldo.

vii

Foreword: Leopoldo De Meis’ Legacy—

A Biochemistry Textbook with a Difference

This is a comprehensive and concise basic Biochemistry textbook for health science

students. This readership is often overwhelmed by conventional textbooks, which

cover many topics in great depth. Indeed, although this information is necessary for

those aiming to become biochemists, it is excessively detailed for the interests of

future nurses, physicians, and dentists. The authors—experienced teachers and

researchers aware of the needs of health science students—have devised a book

specifi cally for this community.

To this end, the book starts off with a description of the molecules of life and

rapidly moves on to cover metabolism and related fi elds, such as the control of body

weight. The book is therefore devoted to human metabolism. Given that its audi￾ence is health science students, only those topics considered of relevance for humans

are presented. One of the hallmarks of current developments in the life sciences is

the merge of classical disciplines. Consequently, the book encompasses pure bio￾chemical information in the framework of related fi elds such as Physiology,

Histology, and Pharmacology. The fi nal chapters on the regulation of metabolism

during physical activity and the control of body weight clearly refl ect this multidis￾ciplinary perspective.

The presentation of metabolism is organized around the concept of the genera￾tion and management of energy. Unlike most textbooks, here the synthesis of ATP

is described fi rst in a very detailed way, after which the metabolic pathways that

feed ATP synthesis are addressed. This logical approach to presenting material was

advocated by Leopoldo de Meis, one of the greatest Biochemistry teachers and

educators of our time. In this regard, this book is a tribute to Leopoldo.

The structural aspects of macromolecules are consistently shown in the fi gures,

and the fundamental notion that reactions are the result of molecular interactions is

reiterated throughout the book. Given that in most university degrees Molecular

Biology and Genetics are now taught in separate courses, the reader is provided

with a description of nucleic acids, faithfully referred to as “Polymers of saccharide

conjugates,” in the chapter dealing with the families of biological molecules.

However, the reader will not fi nd information on DNA and RNA typical of conven￾tional textbooks.

viii

Another interesting feature of the book is the use of “boxes,” which develop

singular concepts in a more informal manner. This presentation technique is highly

illustrative and reader-friendly. Furthermore, key experiments that have opened up

new concepts are explained, thus helping students to appreciate that scientifi c

knowledge derives from the work of researchers, some of which are depicted in

caricatures. Finally, each chapter includes a set of up-to-date and well-chosen refer￾ences, which will help those students wishing to delve further into specifi c fi elds.

In summary, this textbook provides a modern and integrative perspective of

human Biochemistry and will be a faithful companion to health science students

following curricula in which this discipline is addressed. Similarly, this textbook

will be a most useful tool for the teaching community.

Barcelona , Spain Joan Guinovart

Institute for Research in Biomedicine, Barcelona,

Spain, and International Union of Biochemistry

and Molecular Biology, IUBMB

Foreword: Leopoldo De Meis’ Legacy—A Biochemistry Textbook with a Difference

ix

Pref ace

Traditional lecture classes in biological sciences are being challenged by modern forms

of communication. Modern communication tends to be more visual and less interpreta￾tive in nature. In lectures, the didactics are changing vastly and rapidly; the deductive

power of mathematics is complemented by the intuitive clarity of movie simulations,

even if the fi rst is fully embedded in the scientifi c method and the latter are mere artistic

confi gurations of a faintly perceived reality. It is a general trend in modern societies

that the most effective communication is more condensed and focused, contextualizes

the information, and is disseminated across multiple media. Textbooks do not escape

this reality. A modern scientifi c textbook to be effective should be a means of commu￾nication that needs to address specifi c issues of interest, place these issues in a broader

interdisciplinary context, and make use of modern visualization tools that represent

reality within the state of the art available in scientifi c research.

We have shaped this book based on many years of Biochemistry teaching and

researching. We hope to stimulate other teachers to actively rethink biochemical

education in health sciences and “contaminate” students with the passion for bio￾chemical knowledge as an essential part of the indefi nable but fascinating trick of

nature we call life. “We’re trying for something that’s already found us,” Jim

Morrison would say.

Presentation of Book Structure

Our goal in this endeavor is not writing just another piece of literature in bio￾chemistry. We aim at a different textbook. Biochemistry is defi ned as the study of

the molecular processes occurring in living organisms, which means that it com￾prises the network of chemical and physical transformations that allow life to exist.

However, this intrinsic integrative nature of biochemistry may be lost if it is

taught as lists of molecules’ types and metabolic pathways. In this book, we intend

to introduce the biochemistry world in an actual integrative way. For this, our option

was to focus on human biochemistry, presenting the molecular mechanisms of

x

cellular processes in the context of human physiological situations, such as fasting,

feeding, and physical exercise. We believe that this will provide to the reader not

only information but knowledge (as very well represented in the cartoon from Hugh

MacLeod’s gapingvoid).

Reproduced with permission from Hugh MacLeod’s gapingvoid (gapingvoid.com)

The reader will fi nd innovative approaches and deviations relative to the usual

contents of classical textbooks. Part I deals with the importance of molecular-scale

knowledge to reason about life, health, and disease (Chap. 1); the basic chemistry

and physics of living systems (Chap. 2); and the systematization of biomolecules in

chemical families, privileging molecular structure and dynamics instead of dealing

with molecules as shapeless names (Chap. 3). Basic drug discovery concepts are

presented to reinforce the importance of integrative biochemical reasoning. Drug

discovery is a very important part of modern Medicinal Chemistry bridging bio￾chemistry to Pharmacology and Biotechnology. Part I prepares the student for Part

II, which is devoted to metabolisms. Part II starts with the fundamentals of regula￾tion of series of reactions in which kinetic considerations are endowed with math￾ematical accuracy (Chap. 4), and, by extension, the key concepts in the regulation

of metabolism (Chap. 5). To introduce energy metabolism, we fi rst explore the

mechanisms of ATP synthesis (Chap. 6) to create in the reader a need to know from

where cellular energy comes from. The catabolism of major biomolecules follows

naturally (Chap. 7). Metabolic responses to hyperglycemia (Chap. 8), hypoglyce￾mia (Chap. 9), and physical activity (Chap. 10) are used to introduce and contextu￾alize several metabolic pathways, and to illustrate the integrative interplay between

different processes in different tissues. Finally, control of body weight and the mod￾ern metabolic diseases are explored (Chap. 11), placing biochemistry in a human

health perspective, prone to be explored in later stages of health sciences students’

training, when pathologies and clinical problems are addressed.

The option for the integrative view implied that sometimes complex topics have

been reduced to their essence. This is the case of cholesterol synthesis, which is

addressed but not described in detail, and the pentose–phosphate pathway, which

Preface

xi

is presented in the context of fatty acid synthesis, although its other functions are

summarized in a box. For the synthesis of purines and pyrimidines, the reader is

referred to specialized literature. Vitamins are a heterogeneous group of molecules

not directly related to their structure or reactivity; vitamins seen as a family of mol￾ecules is an anachronism and were not the theme of any section of the book. Also,

the reader will not fi nd in this book matters that are typically taught in Molecular

Biology programs such as the replication, transcription, and translation of informa￾tive molecules.

It is also important to mention that biochemical nomenclature is a permanent

challenge for the teacher and the student. The rich history and multidisciplinary

nature of biochemistry have determined that nomenclature is not always clear or

coherent. Coexistence of common and systematic names is frequent and different

names have been consecrated by the use of different communities of biochemists.

The most prominent example is the case of saccharides/sugars/carbohydrates. While

all designations are common, carbohydrates is probably the one preferred by most

professionals in different disciplines. Yet, this name relates to a profound chemical

equivocation of “carbon hydrate”: Many molecules of this family have a

hydrogen:oxygen atom ratio of 2:1 as in water, which makes the empirical formula

C m (H 2 O) n . The illusion of an hydrate is obvious but has no chemical sense.

Respecting the chemical accuracy we preferred the name saccharide in Part I, in

which the chemical nature of biomolecules was presented and discussed, and

reserved the name “carbohydrate” to discuss metabolic processes and dietary impli￾cations, for instance. The use of different names for different contexts and different

implications is intrinsic to biochemistry.

Because biochemistry is made of biochemists and good ideas in addition to mol￾ecules, key historical experiments are used as case studies to ignite discussion and

facilitate learning. Key historical experiments are excellent for classroom use, steer￾ing dynamic discussions between teachers and students. This is the perfect environ￾ment to teaching, learning, and showing that Biochemistry it is not only useful in

shaping the future of humanity, it is also fascinating and appealing.

Urucureá, Brazil Andrea T. Da Poian

Miguel A. R. B. Castanho

Preface

xiii

Acknowledgments

The authors acknowledge the institutional support of CAPES (Brazil) through

Project Ciência Sem Fronteiras PVE171/2012, CNPq (Brazil), Post Graduate

Program on Biological Chemistry of UFRJ (Brazil), Medical Biochemistry and

Biophysics PhD Program (ULisboa, Portugal), Marie Skłodowska-Curie Research

and Innovation Staff Exchange Scheme (Project 644167, European Commission)

and School of Medicine of the University of Lisbon (Portugal). Ms. Emília Alves

(ULisboa, Portugal) is acknowledged for secretariat support. Cláudio Soares (ITQB￾UNL, Portugal) is acknowledged for his critical contributions to some of the

pictured molecular structures. The authors thank Ana Coutinho, Ana Salomé Veiga,

Antônio Galina, Cláudio Soares, and José Roberto Meyer-Fernandes for their criti￾cal reading of the manuscript and helpful suggestions.