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Gene & Protein in Disease Albumin (HSA) binding and health

of HSA produce an increase in ketone bodies from the liver, in terms of both obesity and the age profile. In diabetes,
a preferential metabolite for the lungs, heart, and brain. hepatic production of serum albumin decreases, and it
During ketogenesis, any ketones not metabolized during has been long established that insulin positively controls
illness continue to circulate in excess. Glucagon plays a albumin gene expression . Serious illness in COVID-19
[21]
limited role in ketogenesis during fasting or in response to occurs during the secondary phase when IgG3 cells are
SGLT2 inhibition . The lungs are the primary site of plasma at their highest . In addition, glycosylation of HSA
[7]
[37]
and lymph flow from the liver. The delivery of ketones to decreases available HSA binding.
the lungs is immediate; an excess of ketones may produce A chain of nutrient exchange therefore exists between
ketoacidosis [10,44-47] , while a deficit causes inefficiency in the liver–lungs–heart and the rest of the body, such that
cellular function. A chain of events maintains the normal release of proteins and nutrients of the liver are exchanged
supply of ketones from the lungs and depends on albumin in the lungs before entering the capillary circulation of the
levels. Both ketones and glucose levels are also controlled periphery. The lungs and heart are both ketone metabolizers
by levels of insulin and glucagon secreted from the pancreas
directly into the HPV. Pancreatic plasma is sampled for and therefore have a different dependency on HSA binding
glucose levels from cardiac output and is primarily reactive than the periphery. Maintaining this chain is critical for
to changes in glucose concentrations within one or 2 min the health of the heart and lungs, especially during stress
from detection of plasma restricted to capillaries. However, or illness. As blood flows from one organ to the next in
plasma that flows into the lymph may take many hours in series, binding by albumin and corresponding nutrient
the interstitial lymph circulation. Glucose tolerance is thus binders of nutrients change to reflect the correct medium
one of fast (HPV) and slow correction (HSALNP) with for cell growth and cardiovascular efficiency. It is very
present procedures for glucose stabilization and diabetes important that this chain of binding and concentrations of
only referencing these mechanisms in combination. metabolites is maintained so that individual organs operate
within their correct nutrient medium and pressures.
The safety of raising HSA concentration relies on the
timing of distributed nutrients through the interstitial Ketones, (released concurrently with HSA production),
cells and the constitution of the resulting lymph. Although are preferentially metabolized by the lungs, heart, and
the timing to infuse HSA to the cardiovascular capillary brain during prolonged exercise or when glucose levels
circulation takes a few minutes, the resulting flow drop during illness [9,43,44,46] . Increased synthesis and use of
through the interstitial-lymph circuit takes many hours, ketone bodies as ancillary fuel during periods of deficient
as mentioned above. Many nutrients such as glucose food supply, and low insulin levels causes oxidative
are only partly bound to HSA and their timing through stress in the mitochondria, which initiates a protective
the interstitial/lymph does not follow that of HSA. This response allowing cells to cope with decreased energy
means glucose variations follow discrete timings as lymph availability [9,41,46] . In a normal healthy individual who has a
returns to the venous system slowly. Glucose levels are sedentary lifestyle, ketone levels are balanced by the release
maintained mainly by insulin and glucagon excretion of HSA. Exercise produces a relative drop in pressure in
by the pancreas as well as adrenaline in times of stress. the liver, producing both nutrient-bound has and ketone
Insulin, bound to HSA, is maintained by concentrations bodies. In a healthy individual, any excess acetone from
in the HPV as it passes to the liver. Levels of glucose are ketone metabolism is largely excreted by the lungs, thus
therefore dependent on only the insulin levels in the HPV avoiding ketoacidosis. In a respiratory-compromised
and not the rest of the circulatory system. This is reflected individual, whose the lungs are infected by COVID-19,
in the rapidity of glucose homeostasis. Therefore, in illness any increase in HSA and ketones will result in ketoacidosis
where the lymph flow is irregular, insulin measurements and cellular death. An inverse relationship exists between
[46]
should ideally be taken from the HPV or arterial blood HSA levels and ketosis for Type 2 diabetes . As the
where a more direct relationship exists. In the liver, release of ketones is dependent on natural release of HSA,
insulin promotes glycogenesis, converting glucose to any infused HSA will therefore lead to a drop in ketones
glycogen for storage, thus leading to a reduction of blood as plasma volume increases. In acute respiratory distress
sugar. This feedback loop that regulates glucose is entirely syndrome, this may have a beneficial effect on increasing
dependent on the cardiovascular capillary circulation, as antioxidants and decreasing risk of ketoacidosis. If HSA
the pancreas is primarily sampling glucose through this is administered rapidly, both ketones and glucose may
loop with changes in lymph occurring over the longer require adaptation, either by hormonal influence or direct
term depending on lymph flow. The interdependency of infusion. The ketone-body metabolism is maintained by
insulin, HSA, glucose metabolism, and levels of insulin the anabolic hormone insulin and the primarily catabolic
can also be seen in the age variations in Type 2 diabetes hormones, glucagon, cortisol, catecholamines, and growth

Volume 2 Issue 3 (2023) 5 https://doi.org/10.36922/gpd.0328