Cell Metabolism - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 492

a mannose cap. Complex glycoforms have sugar residues (N-acetylglucosamine, galactose,
and/or sialic acid) added to all branches of the oligosaccharide structure. Hybrid glycoforms
have at least one branch modified with one of these sugar residues and one or more with
mannose as the terminal residue.

10.5. METABOLIC REGULATION

Metabolic regulation is the heart of any living cell. Regulation takes place principally at the
genetic level and at the cellular level (principally, control of enzyme activity and through cell
surface receptors). Let us first consider genetic-level changes, as these fit most closely with
our discussion of transcription and translation.

10.5.1. Genetic-Level Control: Which Proteins are Synthesized?
It is known that the formation of a protein requires transcription of a gene. Transcriptional
control of protein synthesis is the most common control strategy used in bacteria. Control of
protein synthesis in eukaryotes can be more complex, but the same basic concepts hold. In
the simplest terms, the cell senses that it has too much or too little of a particular protein and
responds by increasing or decreasing the rate of transcription of that gene. One form of regu-
lation is feedback repression. In this case, the end product of enzymatic activity accumulates and
blocks transcription. Another form of regulation is induction; a metabolite (often a substrate for
a pathway) accumulates and acts as an inducer of transcription. These concepts are summarized
in Figs 10.12 and 10.13 . In both cases, a repressor protein is required. The repressor can bind to
the operator region and hinder RNA polymerase binding. For repression, a corepressor (typi-
cally the end product of the pathway) is required, and the repressor can block transcription
onlywhen bound to the corepressor. For induction, the inducer (typically a substrate for a reac-
tion) will combine with the repressor, and the complex is inactive as a repressor.
Figures 10.12 and 10.13 show that several genes are under the control of a single promoter.
A set of contiguous genes, encoding proteins with related functions, under the control of

(a)

Promoter Operator Gene 1 Gene 2

Gene 3

RNA
polymerase

Transcription
normally permitted

Repressor

(b)

Promoter Operator Gene 1 Gene 2

Gene 3

RNA
polymerase

Transcription blocked

Repressor

Corepressor

FIGURE 10.12 Process of enzyme repression. (a) Transcription of the operon occurs because the repressor is unable
to bind to the operator. (b) After a corepressor (small molecule) binds to the repressor, the repressor now binds to the
operator and blocks transcription. mRNA and the proteins it codes for are not made.