[Let's look at blood test data!] Focusing on AST and ALT

Last time, we took a deep dive into the "units" and "measurement methods" of blood test data.

Using AST, the familiar "liver value," as an example, I feel I have gained a clearer understanding of its relationship with vitamin B6.

Since we're at it, I'd like to take a deep dive into ALT this time as well, and organize the knowledge needed to read between the lines by using AST and ALT together.

Differences in the personalities of AST and ALT?

Like AST, ALT (alanine transaminase) is an enzyme that cannot function without vitamin B6.

In university lectures, we explain that AST is an enzyme abundant not only in the liver but also in the heart muscle, skeletal muscle, and red blood cells, while ALT is an enzyme with high liver specificity that exists mainly in the liver.

In addition, when reading blood data, we focus on the differences in their personalities.

• AST: A type that holds onto vitamin B6 tightly (strong binding force). It manages to hold on even with a slight vitamin B6 deficiency.

• ALT: A type that lets go of vitamin B6 immediately (weak binding force). When vitamin B6 in the body is insufficient, it is the first to drop vitamin B6 and becomes unable to function.

When a subject who provided a blood sample is suffering from a vitamin B6 deficiency, if measured using the Japanese standard method where the reagent does not contain vitamin B6,

• AST still retains vitamin B6, so it shows a certain level of value.

• ALT easily enters a state where it does not retain vitamin B6 (apoenzyme), so it cannot react with the test reagents (in the case of ALT, L-alanine, α-ketoglutarate, lactate dehydrogenase, and NADH), and the value drops sharply.

Furthermore, in people with a long-term vitamin B6 deficiency, the non-functional apoenzyme ALT is increasingly targeted for degradation, so there is less ALT to begin with.

As a result, the data shows "ALT is extremely low compared to AST".

If the test reagent contained vitamin B6 (world standard method), ALT would also recover and the value would rise, so the extreme "divergence" might not be visible, and it might be difficult to notice.

It is precisely because the Japanese standard method "does not include vitamin B6 in the reagent" that we can read "potential vitamin B6 deficiency" from the data.

Relationship with gluconeogenesis

When ALT is lower than AST, as mentioned above, we consider vitamin B6 deficiency. In addition, from the perspective of molecular nutrition, we also infer, "Could gluconeogenesis be active?"

Why does ALT decrease when gluconeogenesis is active?

The explanation that "ALT is overworked in the glucose-alanine cycle, so it is consumed and decreases" is also often heard.

However, as I learned in chemistry class a long time ago, enzymes are ultimately "catalysts." They are entities that speed up reactions without changing themselves, so I have been feeling uneasy about the idea that "the more you use them, the more they wear out and disappear."

Even without considering such 'depletion,' I wondered if I could explain why 'low ALT levels are often seen in people in states requiring gluconeogenesis, such as hypoglycemia.' Upon investigation, I found that the following explanation is possible.

1. Decrease in enzymes due to a lack of alanine (raw material) (adaptive phenomenon). In a state where gluconeogenesis is actively occurring (meaning the body is desperately making glucose due to energy deficiency), it breaks down muscle and sends a large amount of

alanine to the liver.

If this supply of alanine cannot keep up, the liver might decide, 'Huh? If the essential alanine (raw material) isn't coming, there's no point in having so much ALT ready...'

Since the body dislikes waste, it reduces the synthesis of unnecessary (non-functional) enzyme proteins or accelerates their degradation.

As a result, after long-term increased gluconeogenesis, combined with a decrease in muscle mass and a decline in protein synthesis capacity, it is thought that the total amount of ALT itself decreases (becomes a low value).

2. 'Competition' and 'consumption' of Vitamin B6. For gluconeogenesis, not only ALT but many amino acid metabolic enzymes must be fully operational. Many enzymes that work in the process of gluconeogenesis also all require

Vitamin B6.

Also, the enzyme that breaks down liver glycogen (glycogen phosphorylase), which acts before gluconeogenesis, is said to store and consume the majority of the body's Vitamin B6.

Even if Vitamin B6 is used to break down glycogen, blood glucose is still insufficient
↓
Gluconeogenesis becomes active
↓
Large consumption of Vitamin B6
↓
ALT, which has a weak binding force with Vitamin B6, is the first to have its Vitamin B6 taken away and becomes 'apo-enzymatic (non-functional state)'
↓
ALT becomes low in test data

In other words, it seems we can explain it not as 'ALT itself being depleted,' but as 'Vitamin B6 being diverted to other enzymes due to the emergency of gluconeogenesis, causing ALT to become non-functional, and ultimately appearing as a low value in the data.'

By the way, cortisol, the hormone that commands gluconeogenesis, breaks down muscle (protein) to create alanine, but it also has the effect of inducing (increasing) the synthesis (gene expression) of ALT in the liver.

Therefore, when stress first begins, as cortisol is released and gluconeogenesis starts, ALT actually tends to increase, but

when the body becomes exhausted due to long-term stress or hypoglycemia, and protein deficiency and B6 depletion progress, there is no longer the capacity to make enzymes, and ALT reportedly goes down.

In nutritional guidance, it is sometimes explained as: 'Your ALT is low. In general molecular nutrition theory, such data often suggests that energy consumption is high or you are under stress, increasing the body's demand for Vitamin B6.'

So, when AST and ALT values diverge significantly and AST > ALT, although there are exceptions (elderly/malnutrition/sarcopenia, dialysis, alcohol consumption, muscle, hemolysis, medication, hepatitis, etc.), Vitamin B6 supplementation may be one potential solution.

From the next time onwards, I would like to summarize information about fatty liver, which is also deeply related to AST and ALT!