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Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

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Nội dung chi tiết: Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2s of adenosine triphosphate (ATP) generation, detoxification, and biosynthesis However, when 0: accepts single electrons. Il IS transformed into highl

y reactive oxygen radicals that damage cellular lipids, proteins, and DNA. Damage by reactive OXS gen radicals contributes to cellular death and degen Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

eration in a wide range of diseases (Table 24.1).Radicals are compounds that contain a single electron, usually in an outside orbital. Oxs gen is a bi

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

radical, a molecule that has two unpaired electrons in separate orbitals (Fig 24 I) Through a number of enzymatic and nonenzymatlc processes that rout

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2re readily converted in cells to these reactive radicals. The ROS formed by reduction of 0; are the radical superoxide (O;~), the nonradical hydrogen

peroxide (H:o:), and the hydroxyl radical (OH-)ROS mas- be generated nonenzs maticaily. or enzymatically as accidental byproducts or major products of Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

reactions. Superoxide may be generated nouenzy -maticallyfrom CoO, or from metal-containing enzymes

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

oxidase). The highlv toxic hydroxyl radical is formed nonenzs maticallv from superoxide in the presence of />■1 or Cu ■ by the Fenton reaction, and f

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2damage to proteins and DNA. It also forms lipid peroxides and malondialdehyde from membrane lipids containing polyunsaturated fatty acids. In some cas

es, free radical damage is the direct cause of a disease Slate (e g, tissue damage initiated by exposure to Ionizing radiation). In neurodegener-ative Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

diseases, such as Parkinson s disease, or in ischemia-reperfusion injury. ROS may perpetuate the cellular damage caused by another processOxygen radi

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

cals are joined in their destructive damage by the free radical nitric oxide (NO) and the reactive oxygen species hypochlorous acid (HOCỈ). NOOxygen i

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2airows. It has a tendency to form toxic reactive oxygen species (ROS), such as superoxide (Oj ). the nonradical hydrogen peroxide (H:o:). and the hydr

oxyl radical (OH*).Table 24.1, Some Disease States Associated with Free Radical InjuryAtherogenesisCerebrovascular disordersEmphysema bronchitisIscher Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

Wreperfusion injuryDuchenne-type muscularNeurodegenerative disordersdystrophyAmyotrophic lateral sclerosis (Lou Gehrig’s disease)Pregnancy/preeclampsi

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

aAlzheimer’s diseaseCervical careerDown’s syndromeAlcohol-induced liver diseaseIschemia'reperfusion injury following strokeHemodiatysisOxphos diseases

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2IDATION AND THE GENERATION OF ATPFig 24.2 Oxidative stress. Oxidative stress occurs when the rate of ROS and RNOS production overbalances the late of

their removal by cellular defense mechanisms. These defense mechanisms include a number of enzymes and antioxidants. Antioxidants usually react nonenz Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

ymatically with ROS@The basal ganglia are part of a neuronal feedback loop that modulates and integrates the flow of information from th® cerebral cor

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

tex to the motor neurons of the spinal cord. The neostriatum is the major input structure from the cerebral cortex. The substantia nigra pars compacts

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2riatal pathway). Integrated information feeds back to the basal ganglia and to the cerebral cortex to control voluntary movement. In Parkinson's disea

se, a decrease in the amount of dopamine reaching the basal ganglia results in the movement disorder.I” ventricular fibrillation, rapid pre-J Z'M I ma Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

ture beats from an irritative XJF focus in ventricular muscle occur in runs of varying duration. Persistent fibrillation compromises cardiac output, l

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

eading to death. This arrythmia can result from severe ischemia (lack of blood flow) in the ventricu-lar muscle of the heart caused by clots forming a

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2robably resulted from reperfusing a previously ischemic area of her heart with oxygenated blood. This phenomenon IS known as ischemia-reperfusion inju

ry, and it is caused by cytotoxic ROS derived from oxygen in the blood that reperfuses previously hypoxic cells. Ischemic-reperfusion injury also may Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

occur when tissue oxygenation is interrupted during surgery or transplantation.combines with o: Of superoxide to form reactive nitrogen oxygen species

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

(RNOSf, such as the nonradical peroxynirrite or rhe radical nitrogen dioxide. RNOS are present in the environment (eg. cigarette smoke) and generated

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2myeloperoxidase, and inducible nitric oxide synthase, respectively In addition to killing phagocytosed invading microorganisms, these toxic metabolite

s may damage surrounding tissue components.Cells protect themselves against damage by ROS and other radicals through repair processes, compartmentaliz Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

ation of free radical production, defense enzymes, and endogenous and exogenous antioxidants (free radical scavengers). The defense enzyme superoxide

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

dismutase (SOD) removes the superoxide free radical. Catalase and glutathione peroxidase remove hydrogen peroxide and lipid peroxides I ĩtamin E, vita

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2moval (Fig. 24.2).® (Ị) ®THE WAITING ROOM®Two years ago. Les Dopamau I less dopamine), a 62-year-old man. noted an increasing tremor of his right hand

when sitting quietly (resting tremor). The tremor disappeared if he actively used this hand to do purposeful movement. As this symptom progressed, he Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

also complained of sttffness in his muscles that slowed his movements (bradykinesia). His wife noticed a change in his gait; he had begun taking shor

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

t, shuffling steps and leaned forward as he walked (postural imbalance). He often appeared to be staring ahead with a rather immobile facial expressio

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2and some subtle personality changes (anxiety and emotional lability), she convinced Les to see Their family doctor.The doctor suspected that her patie

nt probably had primary or idiopathic parkinsonism (Parkinson's disease) and referred Mr. Dopaman to a neurologist. In Parkinson’s disease, neurons of Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

the substantia nigra pars compacts, containing the pigment melanin and the neurotransmitter dopamine, degenerate.®Coi a Nail had done well since the

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

successfill lysis of blood clots in her coronary arteries with the use of intravenous recombinant tissue plasminogen activator (TPA)fsee Chapters 19 a

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2ischarge from the hospital. Cora’s cardiologist told her she had developed multiple premature contractions of the ventricular muscle of her heart as t

he clots were being lysed. This process could have led to a life-threatening arrhythmia known as ventricular fibrillation. However. Cora's arrhythmia Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

responded quickly to pharmacologic suppression and did not recur during the remainder of her hospitalization.I. 0? AND THE GENERATION OF ROSThe genera

Ebook Marks’ basic medical biochemistry: A clinical approach (2/E) – Part 2

tion of reactive oxygen species from 0; in our cells is a natural everyday occurrence. They are formed as accidental products of nonenzymatic and enzy

24 Oxygen Toxicity and Free Radical Injuryo is both essential to human life and toxic. If'e are dependent on Ojfor oxidation reactions in the pathways

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