Introduction

Internal cell functions associated with cell growth are not easily measurable; however,
they play important roles in kinetic behaviors. In this topic, the kinetic implication of
endogenous and maintenance metabolism, it will tackle about simplifying the cell
growth-associated functions with a focus on their effects on growth needs.
To harness the free energy produced by catabolic processes in terms of high-energy
phosphate bonds (in particular, in the form of ATP) for subsequent use in the
biosynthesis of biomass constituents in the anabolism, the cellular content of ATP (and
ADP) must be controlled quite rigorously. As the turnover time of ATP is low (Theobald
et al., 1996), there must be a tight balancing of the energy-forming reactions
(catabolism) and the energy-utilizing reactions (the anabolism) inside the cell. In an
analogy to the tight balancing of synthesis and consumption of ATP, the cell needs to
balance the synthesis and consumption of the cofactors NADH or NADPH, which have
a small turnover time. Consequently the cell must exercise a strict control of the level
of these compounds as well.
The balances for ATP, NADH, and NADPH are used to relate the fluxes through
different parts of the metabolic network. However, in order to apply the ATP balance
it is important that all ATP forming and consuming reactions are considered; one group
of energy consuming processes inside the cell, namely the maintenance processes,
is especially important, as it is seemingly a drain on net energy without an apparent
benefit to the system.
Cell Maintenance and Endogenous Metabolism
Cell maintenance is the consumption of a key substrate under consideration to
maintain the desired functionality of the cell in addition to the stoichiometrically
quantifiable desired outcome, such as cell growth. The balance of ATP, NADH, and
NADPH, for example, requires maintenance energy. Endogenous metabolism, on the
other hand, refers to the metabolic needs of a cell to stay viable either by consuming
nutrients in the medium when available or converting intracellular materials when
starved. Therefore, strictly speaking, cell maintenance is cell growth dependent, while
endogenous metabolic needs are often growth independent. Cell maintenance and
endogenous metabolic needs are, however, closely related and not easily separated
in practice. Therefore, these two are often combined in bioprocess modeling, and both
terminologies are used interchangeably at times.
Herbert (1959) showed that it is necessary to consider the endogenous metabolism,
or cell death, when the substrate utilization for biomass growth is to be calculated. He
assumed that this endogenous metabolism results in a decrease of the amount of
biomass, and he described the degradation as a first-order process with a specific rate
of biomass degradation e. Restitution of the degraded biomass requires substrate
and the total substrate consumption is, therefore
-rs = (YFS/X G + YFS/X e)X
Pirt (1965) introduced an empirical correlation identical in form to previous equation
but he collected the product of YFS/x and e in the empirical constant mS:
 -rs = (YFS/X G + mS)X
This empirical constant was called the maintenance coefficient. Strictly speaking,
maintenance requirements and endogenous needs are different, and we tend to
simplify the metabolic system by equate the maintenance and endogenous needs.
This allows us to lump the two different indirect growth needs to one quantity. The
maintenance coefficient can then be related to the specific rate of substrate uptake for
cellular maintenance, via:
|
= = /

Maintenance coefficient (mS) is an important parameter in the fermentation process
and has great influence on the biomass and product yield.
Bauchop and Esden (1960) introduced the concept of ATP requirements for biomass
synthesis via the yield factor YFATP/X and proposed a balance equation that is
analogous to equation introduced by Herbert (1959).
-rs = YFATP/X G + mATP
Here, rATP specifies the total formation rate of ATP in catabolic pathways (different
from the net formation rate of ATP, which is implicitly assumed to be zero in the
equation). From precise measurements of the metabolic products of the anaerobic
metabolism, it is possible to calculate the specific formation rate of ATP, that is, r ATP.
This may be used to find experimental values for YFATP/X and mATP, as shown in many
studies.

The Monod equation is an approximated growth rate from the complicated metabolic
pathways. The same approximation can be applied based on a key intermediate (eg,
ATP), rather than the substrate from the environment. The specific cell growth rate
can then be approximated by:

= =
+
The maintenance cost of the intermediate Y can be assumed to be in a fashion similar
to any other bioreactions. In other words, the maintenance (or endogenous) cost can
be approximated by:

= =
+
Where the saturation constant KeY needs not to be identical to the saturation constant
KY in the cell growth rate. KeY may not be exactly zero either (for which a constant
maintenance coefficient prevails). There are two ways to express the cell maintenance
cost: either to the cell growth rate or to the substrate availability. It is not difficult to see
that:

= =
+
Since cell maintenance goes head to tail with cell growth, substituting the first two
equation:

=
+ ( )

The equation for cell maintenance can be written as:

=
+

Apoptosis
Apoptosis is the process of programmed cell death (PCD) that may occur in
multicellular organisms. PCD involves a series of biochemical events that lead to a
variety of morphological changes, including blebbing changes to the cell membrane,
such as loss of membrane asymmetry and attachment, cell shrinkage, nuclear
fragmentation, chromatin condensation, and chromosomal DNA fragmentation.
Processes of disposal of cellular debris whose results do not damage the organism
differentiate apoptosis from necrosis.
In contrast to necrosis, which is a form of traumatic cell death that results from acute
cellular injury, apoptosis confers advantages during an organisms life cycle in general.
For example, the differentiation of fingers and toes in a developing human embryo
occurs because cells between the fingers apoptose; the result is that the digits are
separate. Between 50 and 70 billion cells die each day due to apoptosis in the average
human adult. For an average child between the ages of 8 and 14, approximately 20
billion to 30 billion cells die a day. In a year, this amounts to the proliferation and
subsequent destruction of amass of cells equal to ones body weight.
Research on apoptosis has increased substantially since the early 1990s. In addition
to its importance as a biological phenomenon, defective apoptotic processes have
been implicated in an extensive variety of diseases. Excessive apoptosis causes
hypotrophy, such as in ischemic damage, whereas an insufficient amount results in
uncontrolled cell proliferation, such as cancer.
Apoptosis occurs when a cell is damaged beyond repair, is infected with a virus, or
has experienced stressful conditions such as starvation. Damage to DNA from ionizing
radiation or toxic chemicals can also induce apoptosis via the actions of the tumor-
suppressing gene.
Apoptosis also plays a role in preventing cancer. If a cell is unable to undergo
apoptosis because of mutation or biochemical inhibition, it continues to divide and
develop into a tumor. For example, infection by papilloma viruses causes a viral gene
to interfere with the cells protein, an important member of the apoptotic pathway. This
interference in the apoptotic capability of the cell plays a role in the development of
cervical cancer.
Before the actual process of cell death is precipitated by enzymes, apoptotic signals
must cause regulatory proteins to initiate the apoptosis pathway. This step allows
apoptotic signals to cause cell death or stop the process should the cell no longer need
to die. Several proteins are involved, but two main methods of regulation have been
identified: targeting mitochondria functionality or directly transducing the signal via
adaptor proteins to the apoptotic mechanisms. Another extrinsic pathway for initiation
identified in several toxin studies is an increase in calcium concentration within a cell
caused by drug activity, which also can cause apoptosis via a calcium-binding
protease calpain.
PCD in plants has a number of molecular similarities to animal apoptosis, but it also
has differences, notably the presence of a cell wall and the lack of an immune system,
which removes the pieces of the dead cell. Instead of an immune response, the dying
cell synthesizes substances to break itself down and places them in a vacuole, which
ruptures as the cell dies.
One can infer that cell death in multicellular organisms is a means to maintain the
overall health of the organism. The energy spent may be termed endogenous
metabolism. This is a magnification of endogenous metabolism in single cells.
 University of Mindanao, Davao City
Engineering Department

In Partial Fulfillment of the Requirement in

Biochemical Engineering
ChE 544

Kinetic Implication of Endogenous and Maintenance Metabolism

Submitted by:
John M. Gohiling

Submitted to:
Engr. Arjan C. Lingaya
Instructor

July 4, 2017