Oxidative Phosphorylation & Phospholipids Flashcards
Define oxidases and give an example
These are enzymes concerned with removal of hydrogen using oxygen as a hydrogen acceptor.
Cytochrome oxidase
Define dehydrogenase and give an example
They transfer hydrogen from one substarate to another (usually a coenzyme as NAD+) in a reversible coupled redox reaction.
Succinate dehydrogenase & mitochondrial glycerol 3-phosphate dehydrogenase which use riboflavin as coenzyme.
Define hydroperoxidases and give an example
They are responsible for disposal of hydrogen peroxide.
Peroxidase and catalase
Define oxygenases and their subdivisions
They catalyze the incorporation of oxygen into substrate molecules.
Di-oxygenase and mono-oxygenase (hydroxylase)
Mention component of ETC
NADH dehydrogenase (complex I) Succinate dehydrogenase (complex II) Cytochrome b-c1 (complex III) Cytochrome oxidase (complex IV)
Describe electron transport in complex I
Electrona move from NADH to FMN to the iron of iron-sulfur centers and then to CoQ. The energy of electron flow is used to transport protons from matrix to intermembrane space.
Describe electron transport in complex II
Succinate dehydrogenase catalyzes oxidation of succinate to fumarate and forms FADH2, then hydrogen atoms are moved to iron-sulphur protein the to CoQ. No protons are pumped by the complex.
GR: CoQ is called ubiquinone
Because it is a quinone dervative, ubiquitous in biologic systems
Mention the mobile components of ETC and their site.
CoQ in inner mitochondrial membranr
and cytochrome c loosely attached to outer aspect of inner mitochondrial membrane.
Describe ET in CoQ
Accepts hydrogen atoms from complex I or II transfers electrons to complex III. It also accepts e from mitochondrial dehydrogenase.
Compare heme of Hb and cytochromes
Unlike iron of heme of Hb, cytochrome iron is reversibly converted from Fe3+ to Fe+2 as a normal part of its function as an acceptor and donor of electrons.
Describe ET in complex III
Electrons move from cytochrome b to iron sulfur center to cytochrome c1 to cytochrome c then to complex IV, the energy of e flow is used to pump protons out of the mitochondria.
Describe electron transport in complex IV
The transported electrons, O2 and free protons are brought together , and O2 is reduced to water.
Mention the gradients created by proton pumps in ETC
Electrical and pH gradients
Mention the role of proton pump in ETC
Serves as a common intermediate that couples oxidation to phosphorylation
Describe the structure of complex V
Consists of Fo which spans the inner mitochondrial membrane and an extra-membranous domain (F1) that appears as a sphere that protrudes into the mitochondrial matrix.
Mechanism of ATP synthesis after pumping protons outside the matrix
They re-enter by passing through a proton channel in the Fo domain driving rotation of Fo, this causes conformational changes in the b-subunits of F1 domain that allow them to bind ADP + Pi, thus ATP is formed.
Mention findings which support the Mitchell theory
Addition of protons to the external medium of intact mitochondrial membrane inc ATP production
Oxidative phoaphorylation doean’t occur in case of solubilization of mirochondrial membrane
Factors controlling respiratory chain
Controlled by availability of ADP and in some cases concentration of inorganic phosphate.
Define uncouplers
Substances which allow protons to leak back into the matrix without going through the ATP synthase (proton channel of Fo domain)
What is the result of uncoupling process
Increased oxygen consumption and heat production as electron flow and proton pumping attempt to maintain the electrochemical gradient. Also, no ATP is produced
Mention examples of uncouplers and their role if possible
- Thermogenin found in brown adipose tissue in newly borns energy is dissipated as heat and no ATP is produces.
- 2,4-dinitrophenol a lipophilic proton carrier that diffuses readily through the mitochondrial membrane.
Mention inhibitors of each complex of ETC
I, barbiturates and rotenone
III, war gas and antimycin A
IV, H2S, CO & CN
Mention an inhibitor of complex V and its mechanism
Oligomycin
Binds to Fo domain of ATP synthase preventing entry of protons thus no ATP is produced
Soon, the ETC stops due to difficulty of pumping electrons against the steep gradient
GR: Although only 13 out of 90 proteins are coded by mitochondrial DNA rather than chromosomal most diseases are caused by mutations to the former.
Beacuse mtDNA has mutation rate 10 times more than chromosomal
Give examples of diseases caused by mutations to mtDNA
Mitochondrial myopathies
Leber hereditary optic neuropathy
GR: mtDNA is maternally inherited
Because mitochondria from the sperm cell do not enter the fertilized egg
The first pathway of phospholipids synthesis begins by the enzyme
Phosphatase
Mention steps of synthesis of phsphatidylcholne, -ethanolamine & -serine.
CDP-choline reacts with DAG giving phosphatidylcholine and releases CMP
CDP-ethanolamine synthesizes phosphatidylethanolamine in the same way
Phosphatidylserine is synthesized from replacememt of ethanolamine by serine in phosphtidylethanolamine
Phosphatidylserine is converted to -ethanolamine by……
Decarboxylation
Phosphatidylethanolamime is converted to -cholineby……where …. is donor
Methylation
SAM
Describe synthesis of cardiolipin and phosphatidyl inositol
CTP reacts with phospahtidic acid giving CDP-diacylglycerol, which reacts either with phosphatidylglycerol to form cardiolipin or inositol to form phosphatidylinsoitol
Mention role of PIP2
Cleaved to DAG and inositol triphosphate (2nd messengers) by phospholipase C.
Infant RDS result from deficiency of …..
Dipalmitoyl lecithin
Describe the measure of lung maturity of fetus
Ratio concentrations of lecithin to sphigomyelin
A ratio of 2 or more indicatea maturity
Mention the role phospholipase A2
Cleaves the FA attached to C2 which is usually an unsaturated FA used in arachidonic acid synthesis, so the enzyme is activated by signals of syntheisi of eicosanoids.
Mention function of phospholipase D
Breaks the bond between phosphate and head groupproducing phasphatidic acid and alcohol of head group.
Describe the mecahnsim of acquired phospholipodosis
Some druga bind to phospholipids and inhibit their hydrolysis by lysosomal phospholipases.
