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Oxidative Phosphorylation and the electron transport chain
Many of the products from glycolysis are then transported to the inner mitochondrial membrane where
they donate electrons to a set of electron carriers known as the electron transport chain (ETC). As
electrons transverse the ETC they lose energy and are coupled to the pumping of protons across the inner
mitochondrial membrane which can subsequently be captured to drive the production of ATP through
oxidative phosphorylation (OXPHOS) in a reaction catalyzed by the enzyme complex ATP synthase [22,23] .

Oxidative phosphorylation is regulated via several mechanisms. The enzymes succinate dehydrogenase
and a-ketoglutarate dehydrogenase have roles in both OXPHOS and the TCA cycle, and are regulated by
TCA intermediates like succinate, fumarate, and a-ketoglutarate. These two enzymes are also inhibited
by high energy compounds and activated by low energy compounds. The pH of the mitochondrial matrix
also regulates OXPHOS, as the ability to maintain the ETC and the subsequent proton pump is tied to
[22]
maintaining a pH gradient .
Gluconeogenesis
Gluconeogenesis is the synthesis of glucose, allowing the body to ensure blood sugar levels remain stable
even in fasting states. The first step in gluconeogenesis is synthesizing PEP from pyruvate. This is a two-step
process in which pyruvate is first converted to oxaloacetate by pyruvate carboxylase, then converted to PEP
by PEP carboxykinase. PEP is converted to 2-phosphoglycerate, and subsequently to 3-phosphoglycerate,
which is phosphorylated to produce 1,2-bisphosphoglycerate. Glyceraldehyde 3-phosphate is then synthesized
by glyceraldehyde phosphatase dehydrogenase and converted to fructose 1,6-bisphosphate. Finally, glucose
6-phosphatase dephosphorylates glucose 6-phosphate to form glucose. Since this process is nearly the
opposite of glycolysis, many of the enzymes between these two processes are the same, and gluconeogenesis
is tightly regulated by many feedback mechanisms to maintain the glucose concentration and to avoid hypo/
hyperglycemia. Not surprisingly then, one of the main regulators of gluconeogenesis is glucose itself; the
other two main regulators are pyruvate and PEP. High concentrations of these two molecules in combination
[22]
with lower levels of glucose leads to increased gluconeogenesis .

Fatty acid synthesis and degradation
Fatty acid synthesis is not only important for long-term energy storage but also for structural components of
cell membranes and eicosanoids. Fatty acid synthesis typically begins with a reaction between acetyl-CoA
and malonyl-ACP to yield acetoacetyl-ACP and CO . This condensation reaction is facilitated by 3-ketoacyl
2
ACP synthase (KAS III). Acetoacetyl-ACP subsequently undergoes reduction, hydration, and re-reduction
to reduce the 3-keto group eventually yielding acyl-ACP, which can be used to initiate elongation of the
fatty acid chain. This cycle continues until acyl-ACP’s backbone reaches 16 or 18 carbons. After appropriate
elongation acyl-CoA can be used for multiple different processes, including synthesis of glycerophospholipids
and triacylglycerides, production of phosphatidate, and synthesis of phosphatidylcholine (PC). While
lipogenesis can occur through the conversion of carbohydrates to acetyl-CoA, it can also take place by de-
novo lipogenesis through the conversion of glycogen to fatty acids which typically occurs when glycogen
[22]
storage is full .

To release energy stored at fat, the molecule undergoes b-oxidation, or fatty acid oxidation. As fatty acids
are unable to diffuse through the mitochondrial membrane, they are first converted to acylcarnitine which
can enter through the carnitine antiports. Once in the matrix, acylcarnitine is converted to fatty-acyl-CoA.
b-oxidation is largely the reverse reaction of lipid synthesis. Starting with acyl-SCoA there is oxidation,
hydration and oxidation again to yield 3-ketoacyl-SCoA. The b-carbonyl is then cleaved by HS-CoA,
resulting in a fatty Acyl-CoA molecule that now holds two less carbons then it did at the start of the cycle.
[22]
Each cycle thus produces ubiquinol, NADH and acetyl-CoA which can all be used in aerobic respiration .