Table of Contents
Fundamentals of Biochemistry
Biochem 380 - Fall 2006
Lecture 021
Outline
- Quiz
- Announcements
- Questions from previous lecture
- Section 7.12: Lipoamide
- Section 7.13: Lipid Vitamins
- Section 7.14: Ubiquinone
- Section 7.15: Protein Coenzymes
- Section 7.16: Cytochromes
Announcements
- Lecture 20 notes are online
Questions
- Any questions on the material from the previous lecture?
Section 7.12: Lipoamide
- Lipoamide is a coenzyme that is bound to a protein chain in the pyruvate dehydrogenase (PDH) complex.
This complex is involved in the conversion of pyruvate to acetyl-CoA in the input to the citric acid cycle
(chapter 13)
- Lipoamide has a long linear chain that is formed by a bond to the ε-amino group at the
end of a lysine side chain. This long chain is believed to function as a swinging arm that moves between
different sites on the PDH complex
- The end of lipoamide contains two sulfhydryl groups in a disulfide linkage. One of the sulfur atoms
reacts with the acetyl group in HETPP to form a thioester, before being transferred to Coenzyme A (CoA)
The Pyruvate Dehydrogenase Complex
Section 7.13: Lipid Vitamins
- So far, all of the vitamins we have discussed are water-soluble. A number of vitamins are
mostly lipid in structure, although they also have polar groups. The lipid vitamins include
the following:
- Vitamin A (retinol and other forms), multiple functions including role in vision
- Vitamin D3 (cholecalciferol), involved in calcium absorption
- Vitamin E (α-tocopherol), an antioxidant
- Vitamin K (phylloquinone), involved in blood-clotting
Vitamin A
- Vitamin A is a lipid molecule obtained from the cleavage of β-carotene, a 40-carbon
lipid found in carrots and other yellow vegetables
- Vitamin A exists in multiple forms, including the alcohol retinol, shown above
- It can be converted into the aldehyde form retinal, which is a light-sensitive
prosthetic group attached to rhodopsin, a protein in the retina
- Another derivative is retinoic acid, which is used as a signaling molecule in multicellular development
Vitamin D
- Vitamin D is another lipid molecule that exists in multiple forms, including vitamin D2
(ergocalciferol) and vitamin D3 (cholecalciferol). These are variants of a hydrocarbon
chain at carbon 17 of derivatives of cholesterol, a 4-ring lipid that is a percursor of many hormones
- Vitamin D is derived from 7-dehydrocholesterol by photochemical cleavage of a bond in the B ring.
This cleavage reaction can be produced by the action of sunlight in the skin. Inadequate amounts of sunlight
can result in vitamin D deficiencies
- Cholecalciferol is subsequently converted to 1,25-Dihydroxycholecalciferol, which is used in regulating
calcium deposition in bones. Rickets is a disease caused by deficiencies of vitamin D that
results in weakening in bones due to improper crystallization of calcium phosphate
Vitamin E
- Vitamin E is a two ring molecule with a hydrophobic tail. The ring system contains a phenol group
that can exist as a stable free radical
- This allows it to function as an antioxidant that scavanges oxygen and free radicals that
can damage fatty acid molecules
- Artificial antioxidants such as BHT and BHA possess similar antioxidant properties, and are added to
foods with oils and fatty acids, to prevent them from becoming rancid
Vitamin K
- Vitamin K is another lipid vitamin. It acts as a coenzyme in a reaction involved in blood clotting
- Blood clotting is a critical protective mechanism in circulatory systems that must be carefully
regulated. Without a clotting capability, a break or cut in the system could result in bleeding to death.
On the other hand, too much clotting can cause heart attacks or stroke
- Consequently, clotting should only occur at actual sites of injury. The conversion of prothrombin
to thrombin is one of the final steps in a cascade of reactions that are required for clotting,
and vitamin K is required for a reaction that modifies glutamate residues on prothrombin
Vitamin K and Blood Clotting
Blood Clotting and Evolution
- Some critics of evolutionary theory have cited the complex, tightly-regulated cascade of enzymes
found in blood clotting as evidence against evolution
- The argument is made that it is highly improbable that such a critical interconnected system could have evolved,
because any harmful mutation to any component would have catastrophic consequences that would result in the immediate
death of an organism, ruling out incremental evolution
- The problem with this argument is that it does not consider how a blood clotting system would
co-evolve with the associated circulatory system
- The failure of a primordial circulatory system in early multicellular organisms would not be catastrophic
during the period of time in which its functional capabilities and selective advantages were still emerging.
Consequently, an associated primordial clotting cascade would be able to evolve incrementally with such a system
- Considering the evolution of a complex blood clotting system as only occurring within the
context of a modern circulatory system is a fundamental flaw in such arguments against evolution
Section 7.14: Ubiquinone
- Ubiquinone is another electron carrier. It is also called Coenzyme Q, or just Q
- It is found in the electron transport chain
- Ubiquinone is a quinone, which is precisely defined as a cyclohexadienedione (or a derivative)
Oxidation States of Ubiquinone
Section 7.15: Protein Coenzymes
- A number of coenzymes are themselves proteins, that can bind as cosubstrates to an enzyme or enzyme complex
- An example is thioredoxin, shown above, which has a reactive disulfide group on the surface of
the protein, where it can be accessible in the active site of an enzyme
- Another example is acyl carrier protein, which is used in lipid metabolism. Its
reactive group is the terminal sulfhydryl group, which can form a thioester linkage to fatty acids
Section 7.16: Cytochromes
- An important class of protein coenzymes are the cytochromes, which are heme-containing proteins
where the bound iron atom Fe(III) can undergo reversible one-electron reduction to Fe(II)
- The term 'cytochrome' refers to the color of the protein on absorption of light. The α band
around 560 nm determines the naming convention of the different cytochromes, which differ in groups
attached to the heme, causing slight variations in absorbance
Cytochrome C is a Soluble One-Electron Carrier
Questions
- Questions about the material covered today?
Next Lecture: Sections 8.1 - 8.3
