Myoglobin and hemoglobin contain heme, an iron-containing cyclic tetrapyrrole consisting of four molecules of pyrrole linked by methyne bridges. This planar network of conjugated double bonds absorbs visible light and colors heme deep red. The substituents at the β-positions of heme are methyl (M), vinyl (V), and propionate (Pr) groups arranged in the order M, V, M, V, M, Pr, Pr, M (Figure 1). An atom of ferrous iron (Fe2+) resides at the center of the planar tetrapyrrole. Oxidation of the Fe2+ of myoglobin or hemoglobin to Fe3+ destroys their biologic activity. Other proteins with metal-containing tetra pyrrole prosthetic groups include the cytochromes (Fe and Cu) and chlorophyll (Mg).

Fig1. Heme. The pyrrole rings and methyne bridge car bons are coplanar, and the iron atom (Fe2+) resides in almost the same plane. The fifth and sixth coordination positions of Fe2+ are directly perpendicular to—and directly above and below—the plane of the heme ring. Observe the nature of the methyl (blue), vinyl (green), and propionate (orange) substituent groups on the β carbons of the pyr role rings, the central iron atom (red), and the location of the polar side of the heme ring (at about 7 o’clock) that faces the surface of the myoglobin molecule.

Myoglobin Is Rich in α Helix

Oxygen stored in red muscle myoglobin is released during O2 deprivation (eg, severe exercise) for use in muscle mitochondria for aerobic synthesis of ATP. A 153-aminoacyl residue polypeptide (MW 17,000), the compactly folded myoglobin molecule measures 4.5 × 3.5 × 2.5 nm (Figure2). An unusually high proportion, about 75%, of the residues are present in eight right-handed 7 to 20 residue α helices. Starting at the amino terminal, these are termed helices A through H. Typical of globular proteins, the surface of myoglobin is rich in amino acids bearing polar and potentially charged side chains, while—with two exceptions—the interior contains residues that possess nonpolar R groups (eg, Leu, Val, Phe, and Met). The exceptions are the seventh and eighth residues in helices E and F, His E7 and His F8, which lie close to the heme iron, the site of O2 binding.

Fig2. Three-dimensional structure of myoglobin. Shown is a ribbon diagram tracing the polypeptide backbone of myoglobin. The color of the polypeptide chain is graded along the visible spectrum from blue (N-terminal) to tan (C-terminal). The heme pros thetic group is red. The α-helical regions are designated A through H. The distal (E7) and proximal (F8) histidine residues are highlighted in blue and orange, respectively. Note how the polar propionate substituents (Pr) project out of the heme toward solvent. (Adapted with permission from Protein Data Bank ID no. 1a6n.)

Histidines F8 & E7 Perform Unique Roles in Oxygen Binding

The heme of myoglobin lies in a crevice between helices E and F oriented with its polar propionate groups facing the surface of the globin (see Figure 2). The remainder resides in the nonpolar interior. It is held in place mainly by hydrophobic interactions. The fifth coordination position of the iron is occu pied by a nitrogen from the imidazole ring of the proximal histidine, His F8. The distal histidine, His E7, lies on the side of the heme ring opposite to His F8.

The Iron Moves Toward the Plane of the Heme When Oxygen Is Bound

 The iron of unoxygenated myoglobin lies 0.03 nm (0.3 Å) out side the plane of the heme ring, toward the proximal histidine, His F8. Consequently, the heme “puckers” slightly. When O2 occupies the sixth coordination position, the iron moves to within 0.01 nm (0.1 Å) of the plane of the heme ring. Oxygenation of myoglobin thus is accompanied by motion of the iron, of His F8, and of residues linked to His F8.

Apomyoglobin Provides a Hindered Environment for the Heme Iron

Minute quantities of CO arise from a variety of biologic sources, including the catabolism of red blood cells within the human body. CO is also present in the atmosphere, mainly due to the incomplete combustion of fossil fuels. CO binds to the iron in a free heme group 25,000 times more strongly than oxygen. However, the heme groups in the apoproteins of myoglobin and hemoglobin reside in a hindered environment for their gaseous ligands (Figure 3). When CO binds to free heme, all three atoms (Fe, C, and O) lie perpendicular to the plane of the heme. This geometry maximizes the overlap between the lone pair of electrons on the sp hybridized carbon of the CO molecule and the Fe2+ iron (Figure 4, right). By contrast, O2 is sp2 hybridized. Consequently, the electrons that bind to the iron lie at an angle of roughly 120° to the axis of the O=O double bond (see Figure 6–4, left). In myoglobin and hemoglobin the distal histidine sterically precludes or hinders the preferred, high-affinity orientation of CO while still permitting O2 to attain its most favorable orientation (see Figure 3). Binding at a less favored angle reduces the strength of the heme-CO bond to about 200 times that of the heme-O2 bond (see Figure 3, right). Therefore O2 , which typically is present in great excess over CO, normally dominates. Nevertheless, about 1% of human myoglobin typically is present combined with CO.

Fig3. Angles for bonding of oxygen and carbon monoxide (CO) to the heme iron of myoglobin. The distal E7 histidine hinders bonding of CO at the preferred (90°) angle to the plane of the heme ring.

Fig4. Orientation of the lone pairs of electrons relative to the O— —O bonds of oxygen and carbon monoxide. —O and C— In molecular oxygen, formation of the double bond between the two oxygen atoms is facilitated by the adoption of an sp2 hybridization state by the valence electron of each oxygen atom. As a consequence, the two atoms of the oxygen molecule and each lone pair of electrons are coplanar and separated by an angle of roughly 120° (left). By contrast, the two atoms of carbon monoxide are joined by a triple bond, which requires that the carbon and oxygen atoms adopt an sp hybridization state. In this state, the lone pairs of electrons and triple bonds are arranged in a linear fashion, where they are separated by an angle of 180° (right).

اخر الاخبار

اخبار العتبة العباسية المقدسة

للحفاظ على سلامتها.. متحف الكفيل يشرع بخطته السنوية لصيانة مقتنياته

شعبة التوجيه الديني تنظّم مسابقةً ميدانية بذكرى هدم قبور أئمة البقيع (عليهم السلام)

العتبة العباسية المقدسة تواصل إحياء ذكرى هدم قبور أئمة البقيع (عليهم السلام)

قسم الشؤون الفكرية يعقد اجتماعه الفصلي الأول لعام 2026م

المزيد

الآخبار الصحية

اكتشاف هام قد يمهّد لعلاج جديد للسمنة

تغييرات بسيطة في نمط الحياة تقلل خطر أمراض القلب بنسبة كبيرة

ليس اللب فقط!.. قشرة وبذور المانغو تخفي فوائد صحية مذهلة

زيادة استهلاك الكالسيوم ومنتجات الألبان يحمينا من مشكلات صحية خطيرة

المزيد

الآخبار التكنلوجية

العلماء الروس يكتشفون طريقة تحسن فرص نجاح زراعة الأسنان

لحظة زمنية خاطفة في الدماغ تتحكم في التعلم والحركة

القمر لم يعد مجرد محطة.. خطوة جديدة تغيّر مستقبل البشرية

العلماء يكتشفون "نوعا جديد تماما" من الكواكب

المزيد

مواضيع ذات صلة

Biochemistry and Biosynthesis of Adrenal Steroids and Testosterone Steroids

Enzymes Employ Multiple Mechanistic Strategies to Facilitate Catalysis

The Oxygen Dissociation Curves for Myoglobin & Hemoglobin Suit Their Physiologic Roles

Control of Heme Biosynthesis

Protein Folding

X-Ray Crystallography

Tertiary & Quaternary Structure of proteins

Proteomics & the Proteome

Mass Spectrometers Come in Various Configurations

Edman Devised the First Practical Method for Peptide Sequencing

Parathyroid Hormone-Related Protein

Parathyroid Hormone