L19: Anabolism, And Regulation Of Metabolism

Question 1

Energy requirements for biosynthesis

Answer 1

Extremely high requirements for energy (ATP) input (most of biosynthetic pathways are endergonic)

Non-growing cells degrade and replace (resynthesise) cellular constituents, requiring ATP input

Question 2

Principles governing biosynthesis

Answer 2

1. Macromolecules are synthesised from limited no. of simple structure units (monomers)
2. Many enzymes are used for both catabolic and anabolic processes
3. Some enzymes function in only one direction in amphibolic pathways
4. Anabolism consumes energy
5. Anabolic and catabolic reactions can be physically separated
6. Catabolic and anabolic pathways use different cofactors

Question 3

1. Macromolecules are synthesised from limited no. of simple structure units (monomers) (principle governing biosynthesis)

Answer 3

Saves genetic storage capacity, biosynthetic raw material and energy

Example: diversity of proteins derived from 20 AA joined by peptide bonds in different sequences. If additional AA were involved, each would require additional genes, enzymes and energy. Similar problems for synthesis of macromolecules-> cellular biosynthesis has evolved efficiency and integration

Question 4

2. Many enzymes are used for both catabolic and anabolic processes (principle governing biosynthesis)

Answer 4

For example:

Most enzymes involved in glycolysis pathway leading to ATP formation from glucose degradation are also involved in biosynthesis of glucose in cell

i.e. many of reaction steps in glycolysis are reversible to achieve gluconeogenesis (glucose biosynthesis)

Question 5

3. Some enzymes function in only one direction in amphibolic pathways

Answer 5

Although many enzymes are shared in amphibolic pathways, some reactions require different enzymes: one for catabolic and one for anabolic

Enables independent regulation of catabolism and anabolism

Example: glycolysis/gluconeogenesis amphibolic pathway. 4 reactions in pathway involve enzymes that differ between glycolytic direction and glucogenic direction

Question 6

4. Anabolism consumes energy

Answer 6

Many reactions in anabolism are endergonic

Energy required to force them in direction of biosynthesis

Energy in ATP used to drive

Question 7

5. Anabolic and catabolic reactions can be physically separated

Answer 7

Biosynthesis and catabolic functions are located in separate organelles in eukaryotes (mitochondria, EF, lysozomes)

Some compartmentation in prokaryotes (ETC localised in plasma membrane, carboxysomes)

Allows some pathways to operate simultaneously but independently

Question 8

6. Catabolic and anabolic pathways use different cofactors

Answer 8

Catabolism produces NADH (NAD acts as an e acceptor)

Anabolism uses NADPH (nicotinamide adenine dinucleotide phosphate) as e donor

Question 9

Precursor metabolites

Answer 9

Generation of precursor metabolites: critical step in anabolism

Are carbon skeletons used as starting substrates for synthesis of macromolecules (proteins, nucleic acids, lipids, polysaccharides)

Are intermediates of glycolytic pathway and TCA cycle -> glycolysis and TCA cycle function to provide energy and provide raw materials for biosynthesis

Question 10

Metabolism regulated in 3 ways

Answer 10

1. Metabolic channeling
2. Regulation of gene expression
3. Posttranslational regulation of enzyme activity

Question 11

Regulation of metabolism

Answer 11

Important for:

Efficiency (conservation of energy and materials). Example: no synthesis of enzymes for which no substrate is available or to produce end products already in abundance

Maintenance of metabolic balance in response to external changes

Question 12

Metabolic channeling

Answer 12

Metabolic pathways are differentially located in different parts of cell.

Example: in eukaryotes lipids are catabolised in mitochondria but synthesised in cytoplasm

Gram -ve bacteria in periplasm (region bounded by cell and outer members) contains many degradative (catabolic) enzymes

This compartmentation (different distribution of enzymes and metabolites among separate cell structures or organelles): common channel mechanism. Facilitates separate operation and regulation of similar pathways; enables enhanced pathway control by regulation of delivery of key metabolites to compartments

Question 13

Regulation of gene expression

Answer 13

Controls synthesis of particular enzyme

Relatively slow, but conserved energy and use of cellular materials

Can occur at transcription and/or translation

E.g DNA binding protein can bind to DNA, preventing or enhancing transcription

Binding of regulatory molecules to mRNA can prevent binding of mRNA to ribosomes, preventing translation

Question 14

Posttranslational regulation of enzyme activity

Answer 14

Involves direct stimulation or inhibition of activity of critical enzymes

Occurs following enzyme synthesis

3 important mechanisms: allosteric regulation, covalent modification of enzymes, feedback inhibition

Question 15

Allosteric regulation

Answer 15

Mechanism of posttranslational regulation of enzyme activity

Most regulatory enzymes are allosteric

Activity altered by small molecule termed allosteric effector: binds non-covalently at regulatory site, changes shape of enzyme and alters activity of catalytic site (+ve effector increases enzyme activity, -ve effector inhibits enzyme)

Question 16

Covalent modification of enzymes

Answer 16

Mechanism in posttranslational regulation of enzyme activity

Covalent bonding of chemical group (phosphate, methyl, adenyl) to enzyme affects its activity

Advantages of method: more sophisticated control, regulation of enzymes that catalyse covalent modification adds second level of control

Question 17

Feedback (end-product) inhibition

Answer 17

End-products inhibit one or more critical enzymes in a pathway: regulates entire pathway, typically involves ‘pacemaker ‘ enzyme (catalyses slowest or rate-limiting reaction in pathway)

Each end product regulates its own branch of branching pathway. Other end products then regulate initial pacemaker enzyme