THE SCIENCE

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In HPU, the enzymes responsible for producing heme in the body don't work properly. This leads to a production line hiccup, with a wonky heme that can't do its job correctly. It messes with oxygen delivery to your organs via the blood, oxygen pumping to the muscles for muscle power, cell energy levels, and detoxification.

Most people with HPU have 3 to 4 of 8 heme-making enzymes that do not pull their weight. So, instead of making heme like a pro, your body cranks out some wonky, folded-up heme that's about as useful as a chocolate teapot. 

Now, HPU warriors still have some properly folded heme; otherwise, they would not be viable. However, the fact that the body cannot correctly build a portion of the heme has further consequences:

Bye-bye, essential nutrients! The stuff that's supposed to be heme but gets mucked up is downright toxic. But don't worry; your body mixes vitamin B6, zinc, and a dash of manganese to turn this toxic sludge into water-friendly, flushed out through your kidneys. And since vitamin B6 and zinc are MVPs for over 300 human enzymes, it's no surprise that replenishing these buddies can lead to a whole carnival of symptom relief. 

Oh, and don't forget about manganese – it's like the superhero swooping in to save the day in your mitochondria, keeping those free radicals at bay and detoxifying like a champ.

In this way, HPU results in massive losses of active vitamin B6, zinc, and to a certain extent also manganese. These losses cannot be entirely balanced by nutrition alone.

Heme is a molecule that contains iron, which is essential for oxygen binding and transport. It is a vital component of hemoglobin, the protein in red blood cells that binds oxygen molecules in the lungs and transports them to tissues across the body, ensuring cells receive the oxygen necessary for proper functioning.

Heme is a substance needed in many parts of the human body. Most people have heard of heme in connection with red blood cells, specifically hemoglobin.

Mitochondria are often referred to as the powerhouse of the cell. They are specialized structures found in most cells and are responsible for producing energy in the form of adenosine triphosphate (ATP) through a process called cellular respiration.

REDUCED OXIGEN UPTAKE

 Hemoglobin carries oxygen throughout our body. It's made up of a central heme molecule surrounded by a protein structure. The heme plays the active role by directly binding to oxygen molecules. If the heme is faulty, it can't bind oxygen effectively, leading to reduced oxygen uptake by the body.

Heme is also present in the human body's muscles. Myoglobin is a protein found in muscle tissues that binds to oxygen and helps facilitate its storage and transport within muscle cells. However, when heme is damaged due to HPU, the muscles receive insufficient oxygen, leading to rapid fatigue.

REDUCED ENERGY PRODUCTION WITHIN CELLS

Heme takes center stage in the mitochondria, which are like the power stations of our cells. These tiny energy factories produce ATP, the fuel that keeps our cells running smoothly. This energy production happens through the respiratory chain, where heme-containing enzymes, tucked away in the inner mitochondrial membrane, work their magic.

ATP stands for adenosine triphosphate. It's often referred to as the cell's "energy currency" because it provides the energy needed for cellular processes. When ATP is broken down into adenosine diphosphate (ADP) and inorganic phosphate (Pi), energy is released, which powers various cellular activities.

REDUCED NEUROTRANSMITTER PRODUCTION
Metabolism of Neurotransmitters Heme is also essential for the body's processing of tryptophan, serotonin, and melatonin.

REDUCED NEUROTRANSMITTER PRODUCTION
Metabolism of Neurotransmitters Heme is also essential for the body's processing of tryptophan, serotonin, and melatonin.

Heme contributes to neurotransmitter production by serving as a cofactor for enzymes involved in synthesizing neurotransmitters such as serotonin and melatonin. Specifically, heme-containing enzymes help catalyze the conversion of tryptophan into serotonin and then further into melatonin. Therefore, without sufficient heme, the production of these neurotransmitters may be impaired, potentially leading to disruptions in various physiological processes regulated by serotonin and melatonin.

SLOWED DOWN DETOXIFICATION

Heme plays a vital role in enzyme activity during the body's detoxification phase I. These detoxifying enzymes are responsible for breaking down substances such as alcohol, medications, and toxic metals. However, when the detoxification enzymes are slowed down in the body due to HPU, oxidative stress levels rise. As a result, free radicals constantly attack cells, leading to potential damage and dysfunction.

REDUCED PRODUCTION OF ESSENTIAL STUBSTANCES
Heme is necessary for the body to produce important substances such as cholesterol, steroid hormones, thyroid hormones, vitamin D, and bile acids..

The abbreviation HPU stands for haemopyrrollactamuria and is named after the compound that is found in the urine of a group of patients, the haemopyrrollactam-complex. This complex chemical compound is not found anywhere else in the body and is probably a waste product of metabolism.

SYMPTOMS

Lack of energy, weakness, fatigue, exhaustion and frequent headaches. Chronic fatigue, sleep disorders, weight disorders. Pain in muscles and joints. Irritability, anxiety, depression.

Haemopyrrollactamuria (HPU) is not widely known or frequently diagnosed in the United States. Although it has been researched and acknowledged within certain medical communities, it still lacks widespread recognition compared to other health issues. However, in Germany, HPU has garnered attention and is being studied and addressed by several healthcare providers. Nonetheless, awareness and comprehension of HPU can differ among healthcare providers and geographic areas.

To understand how KPU develops, let's examine the processes in the liver. Here, detoxification occurs, meaning the liver neutralizes all waste products produced in the body and any ingested toxins, such as mold toxins, medications, or poisonous plants.

Detoxification in the liver: PHASE 1 Detoxification occurs in two phases. In Phase 1, substances are initially transformed. This results in intermediate products, which are sometimes more toxic than the original substances. Therefore, Phase 2 must commence immediately.

Detoxification in the liver: PHASE 2 In this phase, toxins are further neutralized and altered to be excreted later. After this step, the waste product is released into the bloodstream by the liver to be eliminated from the body through the kidneys and urine. To enable Phase 2 of detoxification, a catalyst is necessary. This catalyst is pyridoxal-5-phosphate, or P5P for short. It's an activated form of Vitamin B6.

The conversion of vitamin B6 into P5P primarily occurs in the liver and involves enzymes such as pyridoxal kinase, pyridoxine kinase, pyridoxine 5'-phosphate oxidase, and pyridoxamine-phosphate oxidase.

In humans, the conversion of vitamin B6 (pyridoxine, pyridoxal, and pyridoxamine) into its active form, pyridoxal-5-phosphate (P5P), primarily occurs in the liver and other tissues. The process involves several enzymatic reactions:

1. Phosphorylation: The initial step involves the phosphorylation of pyridoxine (PN), pyridoxal (PL), or pyridoxamine (PM) to their respective 5'-phosphate forms. This step is catalyzed by pyridoxal kinase or pyridoxine kinase, depending on the specific form of vitamin B6.
2. Oxidation: The 5'-phosphate forms of vitamin B6 (pyridoxine-5'-phosphate, pyridoxal-5'-phosphate, and pyridoxamine-5'-phosphate) are further oxidized to P5P. This oxidation step is catalyzed by the enzyme pyridoxine 5'-phosphate oxidase or pyridoxamine-phosphate oxidase, depending on the precursor.

Once converted to P5P, it serves as a cofactor for various enzymatic reactions involved in amino acid metabolism, neurotransmitter synthesis, and other essential physiological processes in the body.

If pyridoxal-5-phosphate (P5P) is missing in the human body, it can lead to various health issues due to the essential role P5P plays as a cofactor in numerous enzymatic reactions. Some potential consequences of P5P deficiency include:

1. P5P is a critical player in the synthesis and metabolism of amino acids, the fundamental building blocks of proteins. A deficiency in P5P can disrupt these processes, leading to a decrease in protein synthesis. This can impact the growth, repair, and maintenance of tissues. 
2. Neurological symptoms: P5P synthesizes neurotransmitters such as serotonin, dopamine, and gamma-aminobutyric acid (GABA). Insufficient P5P levels may result in neurological symptoms such as depression, anxiety, irritability, and impaired cognitive function.
3. P5P is a vital component for the optimal functioning of the immune system. A deficiency in P5P can weaken the immune response, making the body more susceptible to infections and impairing its ability to combat pathogens effectively. 
4. Anemia: P5P plays a role in heme synthesis, which is necessary for producing hemoglobin, the protein in red blood cells that carries oxygen throughout the body. A deficiency in P5P can lead to impaired heme synthesis and anemia, characterized by symptoms such as fatigue, weakness, and pale skin.
5. Dermatological issues: P5P deficiency may manifest in dermatological symptoms such as seborrheic dermatitis, eczema, or dry, flaky skin.

Overall, P5P deficiency can have widespread effects on various physiological processes in the body, potentially leading to multiple symptoms and health complications. It's essential to ensure an adequate intake of vitamin B6 to prevent P5P deficiency and support overall health and well-being.

In some instances, the intricacies of vitamin B6 (pyridoxal, pyridoxine, and pyridoxamine) and pyridoxal-5-phosphate (P5P) levels in the blood can be perplexing. This situation can arise due to a myriad of factors:

1. Impaired conversion: Even though there may be sufficient intake or absorption of vitamin B6, there could be issues with its conversion to P5P. This could be due to genetic factors affecting enzyme activity in the conversion process.
2. Functional deficiency: While total levels of vitamin B6 may be high, the body may not effectively utilize it due to a functional deficiency of P5P. This can occur if factors inhibit the activation of vitamin B6 to its active form.
3. Increased demand for P5P: Certain conditions or metabolic processes may increase the demand for P5P in the body, leading to its depletion despite adequate intake of vitamin B6. For example, increased stress, inflammation, or certain medications may increase the requirement for P5P.
4. Altered metabolism: Metabolic disorders or conditions affecting vitamin B6 metabolism can disrupt the body's balance between vitamin B6 and P5P levels. This could result in high levels of vitamin B6 precursors but low levels of the active form, P5P.
5. Nutrient interactions: Interactions with other nutrients or substances in the body could affect the conversion or utilization of vitamin B6. For example, deficiencies in specific cofactors or minerals necessary for vitamin B6 metabolism, such as magnesium or zinc, could impact P5P levels.

While high levels of vitamin B6 may be detected, the presence of low levels of P5P could indicate a functional deficiency. This could have significant implications for various physiological processes in the body. Therefore, it is imperative to conduct further investigation to determine the underlying cause and address any deficiencies appropriately.