HAEMOGLOBIN SYNTHESIS, by shafiqah zawani :')

Have you ever heard about haemoglobin before? Do you know that haemoglobin actually can be separated into haem group and globin? Each of these groups are synthesis distinctly and combine together to give the function as a haemoglobin. But, each of these groups is define differently as well as the synthesis location and the structure. So, what are these actually? Let’s make it clear one by one!

HAEM

v Haem is actually the component of haemoglobin responsible for binding oxygen.

v It consists of an iron ion that binds oxygen and a porphyrin ring that binds the globin molecules.

v One molecule binds one molecule of oxygen.

v Haem synthesis occur largely in the mitochondria.

GLOBIN

v Globin is one of several polypeptides that are the protein components of haemoglobin in blood.

v Globin synthesis occurs in the polyribosome.

v Globin synthesis first detected in the yolk sac at about 3 weeks gestation.

WHAT ABOUT HAEMOGLOBIN?

Haemoglobin is a protein molecule in the red blood cell that carries oxygen from lungs to the tissues and return carbon dioxide from tissue to lungs to be exhaled out. Molecular weight of the haemoglobin are about 68000 and comprise one third of a red cell. Haemoglobin is formed from the combination of haem and globin. 65% of the haemoglobin will be synthesised in the erythroblast and the remaining 35% at the reticulocyte stage. A normal person would have haemoglobin HB-A that consist of four polypeptide chains a₂B₂ each with have its own haem group. 

	HAEMOGLOBIN SYNTHESIS

HAEM SYNTHESIS

Since there are the terms that unfamiliar for some of you I guess, so here I share with you guys about the mnemonic for each of the process. Hopefully it can help you to remember easily. Happy reading guys!

   1.   SYNTHESIS OF δ-AMINOLEUVELINIC ACID(δ-ALA)

Condensation of Glycine and Succinyl-Coenzyme A with aid of vitamin B6 produce δ-ALA. It is catalysed by ALA synthase.This reaction takes place in the mitochondria.

Glycine + B6 + Succinyl~coA  → δ-AminoLevulinic Acid(δ-ALA)

Mnemonic : "Girly Beautiful Secretary Drive Mitsubishi “

Girly – Glycine
Beautiful – B6

Secretary – Succinyl~coA

Drive – Delta- ALA (δ-ALA)

Mitsubishi – Mitochondria

2. SYNTHESIS OF PORPHOBILINOGEN (PBG)

This reaction takes place in Cytosol. The dehydration of two molecules of δ-ALA to form Porphobilinogen(PBG) by the enzyme ALA dehydrase. The enzyme is inhibited by heavy metal ion lead.

2 (δ-AminoLevulinic Acid) δ-ALA → Porphobilinogen(PBG) + H₂O

Mnemonic : “ Dumb people choose lead “

Dumb – Dehydration delta-ALA (δ-ALA)

People – Produce Porphobilinogen (PBG)

Choose – Cytosol

Lead – Lead inhibits the enzyme for this reaction  

3. FORMATION OF UROPORPHYRINOGEN (UPG)

The condensation of four molecules of Porphobilinogen(PBG) forms four molecules of Uroporphyrinogen-III(UPG-III). This reaction catalyzes by Uroporphyrinogen-I synthatase and uroporphyrinogen-III cosynthatase which takes place in cytosol.

          4 (Phorphobilinogen)PBG →4 (Uroporphyrinogen-III) UPG-III

Mnemonic : “ Celcom Prepaid Unlimited Call “

Celcom– Condensation

Prepaid – Porphobilinogen (PBG)

Unlimited – Uroporphyrinogen(UPG) forms

Call – Cytosol


4. SYNTHESIS OF COPROPORPHYRINOGEN (CPG)

Four molecules of Uroporphyrinogen-III(UPG-III) is decarboxylated to four molecules of corpoporphyrinogen(CPG) by uroporphyrinogen decarboxylase. This is the last step in the cytosol.

          4 (Uroporphyrinogen-III) UPG-III→ 4 (Coproporphyrinogen) CPG

Mnemonic : “ Ugly Duckling Chase Cat“

Ugly– Uroporphyrinogen(UPG)

Duckling – Decarboxylate

Chase  – Coproporphrinogen(CPG) forms

Cat – Cytosol


5. SYNTHESIS OF PROTOPORPHYRIN

Four molecules of Coproporphyrinogen(CPG) is converted to four molecules of proporphyrinogen-IX by a reaction catalysed by coproporphyrinogen oxidase  in the mitochondria. Four molecules of Protoporphyrin is the final product of the pathway into which iron is incorporated. Protoporphyrin is synthesised by the action of protoporphyrinogen oxidase. 

Mnemonic : “4 Cooper converted to Proton Preve “

4- 4

Cooper – Coproporphyrinogen (CPG)

Converted – Converted

To – To

Proton Perdana - ProtoPorphyrin


6. FORMATION OF HEME

4 molecules of Protoporphyrin combine with iron in the ferrous state (Fe²⁺) to form haem. It produces 4 molecules of haem.

              4 (Protoporphyrin) + Fe²⁺ → 4 HAEM

Mnemonic : “Prince Charming With Iron Heart “

Prince – Protoporphyrin

Charming – Combine

With – With

Iron – Iron

Heart – Haem forms

Iron is bring to the red blood cells by transferrin protein. Similarly, transferrin protein act like a bus. It takes up the iron from the storage in the liver and the intestine. Then, transferrin protein enter the cytosol and release the iron. Next, transferrin protein will return back to the cycle to take up another iron.

As you can see there is another protein in the cytosol and some of the iron will go to the ferritin protein or out from it. So, basically ferritin protein act as temporary storage in erythroblast. If iron transported by the transferrin protein is not enough for the reaction, ferritin protein will release the iron from it. Somehow if iron is excess for the reaction, ferritin protein will store the excess iron and release it when needed.

GLOBIN SYNTHESIS

1. Amino acids move to ribosomes for protein synthesis.

2. Ribosomes produced Alpha and beta chains of globin proteins.

3. Alpha and Beta chains make up the globin genes which is a₂B₂ that present in normal  person.
4. Haem ( protoporphyrin + Fe ) in haem synthesis combine with globin to make up the haemoglobin.

I  know some of you are wondered about the normal haemoglobin in our body. So here it is!

BE CAREFUL WITH YOUR PALE FACE!!

     Since we are in this topic, I'm glad to share with you guys about the experience related to this. So one day, I was late to the class because I was overslept on that day. I was rushing because my class starts at 8am and it’s already 8.05 when I just left my house. So my friend and I were speeding so we can reach to the class not less than 15 minutes. Our class at level 8 but since we are too late so we decided to use the stairs instead of using the lift. It might takes a long time to wait for the lift and the lift always full because it’s still early in the morning. As we climbed up the stairs, I noticed that my friend’s face looked very pale.  I tried to find from her why was she looking so pale. I probed her to find out if she felt tired after climbed up the stairs because it just 2 levels when I noticed her. But she just silent so I did not ask too much. There’s no one still energized right after climbed up 8 levels of stairs so I guess it is a normal condition.  After half time of the lessons in the class, I still notice that her face looked very pale. So, I ask her what happens to her because the pale seems very obvious. You know her pale was like the vampire and this time, she said she feels lethargic throughout the day and can’t walk for more than 10 minutes. She felt breathless. So after class, I accompanied her to the clinic for haemoglobin check up. I was like thunderstruck when I found that her haemoglobin result was just at 9. She was definitely anaemic. The ideal range for women as you all would be aware should be above 12-16mg/dl, for children 11-13mg/dl and for males 14-18mg/dl.

I told her about haemoglobin boosting foods which I would like to share with you all here. The principle that I hold throughout my life is “nourish your body with a good dose of iron through nutrition rather than popping in supplements”. For me, why should we take the supplements that contains unknown chemicals sometimes or any unknown ingredients while we just can get all those the nutrition from the vegetables and fruits. They are pretty healthy than those of the supplements. I am telling you this because I would like to spread the idea of inculcating good habits among people, motivating people by spreading positive vibes without they having to make any drastic changes to their lifestyle. For me, I feel like spreading the positivity helps one to be self-motivated. So, let’s booster our healthiness together!

1. GARDEN CRESS SEEDS

Few years back, this seeds were not commonly known. As the awareness on health is spreading, this seeds have created its own space in the fitness industry. It is known as Halim (Hindi) or Aliv (Marathi). It is one of the richest vegetarian sources of iron with good bioavailability. 100gms of garden cress seeds provides 1.5mg of iron. It is often given during pregnancy and also it acts as Galactagogue which stimulates milk production in lactating mothers. Daily recommendation is 2 tablespoon. You need to soak the seeds for a while so that it emanates less heat. If you are trying for the first time, start with ½ tablespoon to see if your boy easily accepts it because of its heat. You can have garden cress in different forms such as it can be added in kheer, ladoos and be sprinkled on salads.

2. HAEME IRON

It includes liver, oysters, red meat. Liver (beef and chicken) gives roughly around 23mg of iron in 100 gms. Oysters give around 28mg of iron in 100 gms. However, as we know these foods are very high on cholesterol and saturated fats. The frequency of these meats should be minimal. Once in a week 2 medium pieces can be consumed. Also, try to go for either grilled or baked or steamed to make it healthier.

3. PUMPKIN SEEDS

Like garden cress seeds, these seed are gaining popularity these days. 100 gms of pumpkin seeds serves around 8 mg of iron. Pumpkin seeds are not only rich in iron but also in calcium, magnesium, and manganese and iron. Include at least 2-3 tablespoons in your daily routine. You can have it as a mouth freshener or else sprinkle it over salads.

4. SPINACH

100 gms of cooked spinach gives around 3.75mg of iron. It is packed with calcium and fiber too. So, next time don’t forget to add this lovely looking greens in your salads or soups and veggies.

5. DARK CHOCOLATE

To your surprise, dark chocolate with 75-80% cocoa contains around 17mg of iron. It is also packed with antioxidant. Next time, you can enjoy dark chocolate without any guilt. While savouring, portion needs to be monitored. You can have 2-3 pieces of the chocolate.

The daily recommendation allowance (RDA) for iron:

Adequate Intake (AI)

In animal foods, iron is often attached to proteins called heme proteins and referred to as heme iron. In plant foods, iron is not attached to heme proteins and is classified as non-heme iron. Heme iron is typically absorbed at a rate of 7-35%. Non-heme iron is typically absorbed at a rate of 2-20%.

Vitamin C rich foods like kiwi, amala, lemon, guava, strawberries, sweet lime, oranges enhances the absorption of iron. Henceforth, whenever you consume any iron rich food, don’t forget to have a glass of lemon water along with it which would double up the absorption of the iron.