BCCB2000 Lecture 15: Concepts of Metabolism

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Concepts of Metabolism
Dr Steven Bottomley
Why Study Metabolism?
-Allows us to see how life works
-Defects in metabolism lead to disease and pathology
-Metabolism determines what is happening in a cell at a particular time under
particular conditions
-Metabolites from metabolism can be used for diagnosis
-Metabolism can be used to study the effects of drug treatments
-Metabolism may eventually allow us to propose a ‘theory of life’
Metabolism and Disease:
-Need to know about normal metabolism to understand abnormalities due to
disease
-Normal metabolism adapts of changes in environment including
oExercise
oStarvation
oPregnancy
-Abnormal metabolism is due to such things as
oAbsence of essential nutrients
oDeficient or damaged enzymes
oAbnormal hormone levels
oAction of drugs
oAction of toxins
Overview of Metabolism:
-Metabolism is a network of thousands of enzyme catalysed chemical reactions
occurring in the living cell
-A large number of the reactions can be classified to be either anabolic or
catabolic with respect to the synthetic and breakdown processes respectively
that take place in the cell
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-Chemical reactions in the cell occur as ‘pathways’ i.e. a particular sequence of
chemical reactions
-Metabolism is the result of natural selection selecting for the optimal pathway
-The reactants and products of metabolism are also known as the metabolome
-Metabolism describes the flow of matter and energy within an organism
Metabolism Reductionist and Systems Biology:
-Biochemistry and the analysis of life
oInvestigates individual ‘pieces’ of a massively complex ‘jigsaw’
describing life
oA reductionist approach
oVery successful
-Systems biology
oAttempts of bring the ‘jigsaw’ pieces together to explain life as complete
interacting systems
oInvolves knowing more about metabolic pathways
Their composition and their regulation
The genome, proteome, and metabolome
Metabolism  Proteins and Small Molecules:
-Metabolism involves both proteins and small molecules (metabolites)
-Proteins (in particular enzymes) determine the flow of matter and energy
through the (small molecule) metabolic network
-The total complement of proteins in an organism or cell is called the proteome
-The total complement of metabolites in an organism or cell is called the
metabolome
-There are differences between the genome and proteome
Genome vs. Proteome:
Genome Proteome
One dimensional and finite  the
same in each cell of the organism
Multidimensional  different for each
type of cell in the organism
Constant  ensure fidelity of the
organism
Constantly changing  varies according
to developmental, physiological,
environmental, and pathological
conditions and signals
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Sequence based framework for protein
expression
Operational details of protein expression
 including protein-protein interactions
No indication of transcription,
translation, or post-translation effects on
protein abundance
Consequence of differential effects of
transcription, translation, post-
translation, and degradation on protein
abundance
Relatively simple  40 000 + genes Complex  40 000 + proteins and their
multiple interactions
Proteome:
-Different cells express (synthesise) different proteins, or the same proteins in
different amounts, at different times
oEven the same ‘type’ of cell can be different from a similar cell in a
tissue depending on types and amounts of proteins expressed at a
particular time
-This ‘differential expression’ of a protein by a cell is what makes one cell
different from another, one tissue different from another, and one organism
different from another
oThis is the process of ‘differentiation’
Other Types of ‘Omics’:
-‘Partial’ proteome categories include:
oSecretome (proteins secreted by the cell)
oPeptidome (small molecular weight peptides)
oPhosphoproteome (collection of phosphoproteins)
oGlycoproteome (collection of glycosylated proteins)
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Document Summary

Allows us to see how life works. Defects in metabolism lead to disease and pathology. Metabolism determines what is happening in a cell at a particular time under particular conditions. Metabolites from metabolism can be used for diagnosis. Metabolism can be used to study the effects of drug treatments. Metabolism may eventually allow us to propose a theory of life". Need to know about normal metabolism to understand abnormalities due to disease. Normal metabolism adapts of changes in environment including: exercise, starvation, pregnancy. Abnormal metabolism is due to such things as: absence of essential nutrients, deficient or damaged enzymes, abnormal hormone levels, action of drugs, action of toxins. Metabolism is a network of thousands of enzyme catalysed chemical reactions occurring in the living cell. A large number of the reactions can be classified to be either anabolic or catabolic with respect to the synthetic and breakdown processes respectively that take place in the cell.

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