Passage 8: Glycolosis
“Understanding acid-base regulation is often reduced to pigeonholing clinical
states into categories of disorders based on arterial blood sampling. An earlier
ambition to quantitatively explain disorders by measuring the production and
elimination of acid has not become standard clinical practice. Seeking back to
classical physical chemistry we propose that in any compartment, the requirement
of electroneutrality leads to a strong relationship between charged moieties”.
Hypoxia inhibits the tricarboxylic acid (TCA) cycle and leaves glycolysis as the
primary metabolic pathway responsible for converting glucose into usable energy.
However, the mechanisms that compensate for this loss in energy production
due to TCA cycle inactivation remain poorly understood. Glycolysis enzymes
are typically diffuse and soluble in the cytoplasm under normoxic conditions. In
contrast, recent studies have revealed dynamic compartmentalization of glycolysis
enzymes in response to hypoxic stress in yeast, C. elegans and mammalian
cells. These messenger ribonucleoprotein (mRNP) structures, termed glycolytic
(G) bodies in yeast, lack membrane enclosure and display properties of phaseseparated biomolecular condensates. Disruption of condensate formation
correlates with defects such as impaired synaptic function in C. elegans neurons
and decreased glucose flux in yeast. Concentrating glycolysis enzymes into
condensates may lead to their functioning as ‘metabolons’ that enhance rates of
glucose utilization for increased energy production.
Glycolysis is a core energy-producing pathway in cells; it converts glucose to two
net ATPs and pyruvates, which can then be utilized by the mitochondria to generate
an additional 34 ATPs through oxidative phosphorylation in the tricarboxylic acid
(TCA) cycle. Glycolysis and its related pathways are shown in Figure 1.
Hypoxic stress precludes the function of the highly efficient oxidative
phosphorylation pathway and limits energy production to glycolysis. Despite
substantial work on cellular adaptations to hypoxia, how cells compensate for this
decreased energy efficiency is not fully understood.
In cancer cell lines, both glycolytic and gluconeogenic enzymes localize to puncta
called glucosomes. Furthermore, many enzymes are shared between the opposing
gluconeogenesis and glycolysis pathways, with allosteric regulation of human
phosphofructokinase (PFKL, glycolysis) and fructose-1,6-bisphosphatase (FBPase,
gluconeogenesis) largely governing which pathway predominates. Both of these
enzymes localize to glucosomes, in addition to phosphoenolpyruvate carboxykinase
(PEPCK) and PYK; therefore, allosteric regulation of these enzymes within granules
may influence flux through the opposing pathways.
Source: Fuller & Kim (2021), Compartmentalization and metabolic regulation of
glycolysis.
Which of the following could be a result of a lack of oxygen in the cell?
I. Phosphoglycerate kinase compartmentalization
II. Inhibits the pathway that produces two pyruvate
III. Inhibits the pathway that produces 34 ATPs
A) I, II, and III
B) I and III
C) I and II
D) only I
Correct answer: B.
First, it is important to notice that this question is a Roman numeral question,
which means that it’s best to analyze the option choices first to see which Roman
numeral appears the most. In this case, it is the Roman numeral I. This will be the
Roman numeral that will be analyzed first. The question stem asks what will happen
if there is a lack of oxygen, which is another phrase for describing hypoxic stress.
It is always important to translate the information in the passage into your own
words and vice versa to easily understand terms or phrases presented. This is
the correct answer because, as the passage states, hypoxic stress initiates the
compartmentalization of glycolysis enzymes. Since phosphoglycerate kinase is
one of the enzymes in the pathway, it mobilizes to a specific area of the cell, thus
making the statement I correct. When analyzing statement II, it’s important to realize
that the pathway that produces two pyruvates is glycolysis, and since the passage
states that hypoxic stress only allows glycolysis to proceed, we know that it likely
doesn’t inhibit glycolysis. When analyzing statement III, it’s important to recognize
that the pathway in question is the TCA cycle and oxidative phosphorylation, and
this pathway is known to be inhibited by hypoxic stress, according to the passage.
Therefore, statement III is correct. Therefore, option B is the correct answer
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