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Welcome to Biochemistry 432/832. Instructors: Vadim Gladyshev Lori Allison Teaching Assistant: Yun Jeong Kim yjkim@unlserve.unl.edu Class web page : http://www-class.unl.edu/bioc432/bioc432.htm Tuesday/Thursday 11.00-12.15 pm Beadle Center Auditorium. Outline. Information Syllabus

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Welcome to Biochemistry 432/832

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Welcome to Biochemistry 432/832

Instructors: Vadim Gladyshev

Lori Allison

Teaching Assistant: Yun Jeong Kim

yjkim@unlserve.unl.edu

Class web page: http://www-class.unl.edu/bioc432/bioc432.htm

Tuesday/Thursday 11.00-12.15 pm

Beadle Center Auditorium


Outline

Information

Syllabus

Student profile

Introduction to the course

Introduction to metabolism

Overview of glycolysis


Useful web sites

THE LITERATURE OF BIOCHEMISTRY

http://www-class.unl.edu/bioc839/literature.html

THE FIELD OF BIOCHEMISTRY

Major Journals

Major Reviews

YOUR OWN FIELD OF RESEARCH

REVIEWS

KEY WORD SEARCH

WHERE TO SEARCH?

How to Read a Research Article

Composition of a full paper

Composition of a communication

What to read?

Skepticism


Useful web sites

National Center for Biotechnology Information (NCBI)http://www.ncbi.nlm.nih.gov

Access to the primary literature (Pubmed)http://www.ncbi.nlm.nih.gov/PubMed/

On-line journalsJ. of Biol. Chemistryhttp://www.jbc.org/

Proc. of the Nat. Acad of Sci. USAhttp://www.pnas.org/

Sequences (Entrez)http://www.ncbi.nlm.nih.gov/Entrez/

Structures (Structure)

http://www.ncbi.nlm.nih.gov/Structure/

Clusters of orthologous groups (COS)http://www.ncbi.nlm.nih.gov/COG/


Information

You are welcome to come without an appointment, but it is better to E-mail or call before you come

You are responsible for all material covered in the chapter that is discussed in the class. You will have the reading assignment for each class period except exams.

Some sections of certain chapters may be excluded from the reading assignments and exams, and if it happens, I will tell you beforehand.

No excuses for missing exams. Medical school interview is not an excuse.


Information

Recent scientific papers that describe discoveries or breakthroughs in areas being covered during the course, will be discussed and corresponding concept questions may be included in the exams and bonus questions.

Methods to study: read the chapter (reading assignment) before the respective class period. First, you could read quickly the chapter to get an idea what is it about. The second time you read, pay a particular attention to concepts, but knowledge of details may also be necessary. After the class, read the chapter again and also read the lecture notes. It should be enough for a good performance on exams.


Overview of Metabolism


Metabolism - Overview

Metabolism is a sum of chemical changes that convert nutrients into energy and finally to complex finished products of cells (The process through which organisms acquire and utilize energy for their function)

Do we know all metabolic pathways?


  • Metabolism consists of catabolism and anabolism

  • Catabolism: degradative pathways

    • Usually energy-yielding!

  • Anabolism: biosynthetic pathways

    • energy-requiring!

Metabolism - Overview


Metabolism - Overview


Degradation:

biomolecules –

building blocks – common intermediates -

final products


Principles:

Metabolic pathways are irreversible (because they

must be regulated)

Metabolic pathways have (first) committedstep

Metabolic pathways are regulated

Metabolic pathways are compartmentalized

Metabolism - Overview


Principles: anabolic and catabolic pathways must differ in at least one step in order to be regulated

Anabolic & catabolic pathways

involving the same product are

not the same

Some steps may be common

Others must be different- to ensure

that each pathway is spontaneous

This also allowsregulation

mechanisms to turn one pathway

and the other off


Principles:

Metabolic pathways are compartmentalized

Mitochondria (TCA cycle, OxPhos, fatty acid oxidation, amino acid breakdown)

Cytosol (glycolysis, fatty acid biosynthesis, pentose phosphate cycle)

Nucleus (DNA replication, transcription, RNA processing)

ER (Rough ER: synthesis of membrane and secretory proteins, smooth ER: lipid and steroid biosynthesis)

Golgi (posttranslational processing of proteins)


Pathways consist of sequential steps

- The enzymes may be separate

- Or may form a multienzyme complex

- Or may be a membrane-bound system

- New research

indicates that

multienzyme

complexes are more

common than once

thought


Understanding of pathways:

Sequence of reactions

Mechanisms of each reaction

Regulation of pathways

Metabolism - Overview

  • Hypotheses or exploration ???

Methods:

Inhibitors (accumulation of intermediates)

Genetic defects (also accumulation of intermediates)

Genetic manipulations: animals (transgenic, knockout), expression in certain tissues

Emerging methods: sequence methods (genome projects),

bioinformatics, high throughput gene expression methods

(microarray analyses - hybridizations on membranes, slides, chips)


Systems Analysis of Metabolism

Catabolic and anabolic pathways, occurring simultaneously, must act as a regulated, orderly, responsive whole

  • catabolism, anabolism and macromolecular synthesis

  • Just a few intermediates connect major systems - sugar-phosphates, a-keto acids, CoA derivatives, and PEP

  • ATP & NADPH couple catabolism & anabolism

  • Phototrophs also have photosynthesis and CO2 fixation systems


Intermediary metabolism


Metabolism - energy considerations

  • Cells need a constant supply of energy

  • NADH, NADPH and ATP

  • ATP - energy currency

  • NADPH - reducing power

  • Glucose --> NADH --> ATP

  • Glucose --> NADPH --> biosynthesis (reductive)


Redox in Metabolism

  • NAD+ collects electrons released in catabolism

  • Catabolism is oxidative - substrates lose reducing equivalents

  • Anabolism is reductive - NADPH provides the reducing power (electrons) for anabolic processes

NAD+/NADH ratio: 725Concentration: 0.5 mM

NADP+/NADPH ratio: 0.015Concentration: 0.2 mM


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