278 CHAPTER EIGHT Carbohydrate Metabolism
Glycogen H"'o . ---..... koaso .. � glucose Gluc _::;;. ose-1-pho.,.,,1e · � \ ------Gluc ADP") ' ose 1' f t , UTP---)� Glucose-6-phosphate �PP \ ,, '\J7 _,r � ' t � Fructose-6-p♦ CP Glucose- hosphate 6-phosphatase - ATP I PFK �� - Fructose 1 � ) bisphosphate -�� phosphatase Fructo se-1,6-blsphosphate f Glycera/ dehyde-3-phosphate:t A. ) ◄ Dlhydn,x""'°"" .. !::, p phosphate +�� :.----- + � � �+(H+ Glycera te-11,3-b1lsp hosphate- • ATP • �,rcATF Gly cerate-3-phosphate l Giyc t erate-2-phosphate
Pho�sphoenoll- ----=:-- lpyruvate
Certain ATP ◄ amino ,P, + aclda �_/
FIGURE 8.10 �• The Role of Dopamine in Parkinson's Disease Carbohydrate Metab and Schizophrenia olism: Gluconeogenesls a In nd Glycolysls :ophrenia is a debilitating mental disorder that affects gluconeogenesis, which Parkinson's disease is somewhat better understood and occurs when blood sugar &>crcent of of glycolysis are revers levels arelo w and liver the population worldwide. Its symptoms is believed to arise from decreased dopamine activity in ed. Three irreversible gly glycogen is deplered, 7 of hide substrates forgluc on colytic reacrions arebyp rhe 10 reactions hallucmations, delusions, disordered thinking, another part of the brain. Parkinson's disease is a chronic eogenesis are certain ami assed by alternative reaction cells), and glycer no acids {derived from s. The major rmenr disorders, and social withdrawal. The disease ol {produced from the deg muscle), lactate (formed in neurodegenerative disease characterized by a loss of coor occur only in radation of triacylglycero muscle and red blood s ri e d cytoplasm. the gluconeoge fs). In concrnst to the re iy t k s during late adolescence to early adulthoo . dination and movement. The disease tends to strike after carboxykinas nesis reactions catalyzed actions of glycolysis, which cause e occur within rhe mitoch by pyruvate carboxylase of schizophrenia is still unknown, although an the age of 60. Symptoms of Parkinson's disease include plasmic ondria. The reaction catal and, in some species. PEP reticulum. Note that glucon yzed by glucose-6-phos of the neurotransmitter dopamine appears to be conver eogenesis and glycolysis phatase takes place in the endo l tremor (shaking), bradykinesia (slow movement), rigidity ted either to acetyl-CoA do nor occur simultaneous ved. {not shown) or to lactate. ly. In glycolysis, pyruvare is (stiffness of limbs), and impaired balance. About 60,000 BIOMOLECULES SUMMARY 7 • ORGANIC CHEMISTRY AND 331 330 cannot be administered as a drug because it can't cross the Figure 7-61. Stimulation of this particular neuronal path blood-brain barrier. Instead, the drug L-dopa is adminis• way is associated with feelings of reward and desire, tered. The only difference between the chemical structure memory, and motivation. By binding to the dopamine of L-dopa and dopamine is the carboxylic acid functional receptor in this neuronal pathway, antipsychotic medica• group in L-dopa . The carboxylic acid is removed in a tions prevent dopamine from binding to its receptor. The biochemical reaction in the neuron that converts t-dopa first generation of antipsychotic drugs bound to all dopa into dopamine: mine receptors in the brain, including those in the neuro• nal pathway that control movement (shown in red in HO · �: HO�� Figure 7-61 ). Consequently, some of the side effects of ...., II 'n these drugs were tremors a nd other symptoms like those . ·erve j, Oil D'): - from Parkinson's disease. The newest class of anripsychotic impulse Axon HO HO l.•OOl'A medications, known as terminal J>op.t11:111k: atypical atttipsychotics, block dopamine receptors but specifically target a type of dopa• The prolonged use o Synaptic f L-dopa eventually reduces its ability mine receptor that is found only in the neuronal pathway deft to activate the dopamine receptor. At that point other associated with schizophrenia (shown in green). Therefore, drugs arc usually prescribed. Unfortunately, dopamine Receiving atypical antipsychotic drugs have fewer movemenNelated neuron receptors eventually become less sensitive to these drugs side effects. too and symptoms of the disease return. � There have been significant advances in the treatment The thought disorders associated with schizophrenia of these two ci between neurons. diseases as s entists have unraveled the Figure 7-60 Communication are believed to result from the opposite effect: an excess chemistry behind each of these diseases. Further research of qopamine activity in another neuronal pathway in the pathway. The should eventually lead to even better treatment options known as a neuronal creating what is brain that involves dopamine, highlighted in green in for nosed in the next, a neuronal these patients in the future. disease arc diag impulses through s of Parkinson's a ission of electrical new ca es tr nsm onse. The o physiological resp every year. ultimately leads t a United States two very pathway amine as a son's disease are in the brain that use dop Schizophrenia and Parkin two neuronal pathways an imbalance of dopa· in Figure 7-61. diseases, but both involve are highlighted different essential neurotransmitter Parkinson's Summary a neurotransmitter ent associated with in the brain. Dopamine, The impaired movem mine in the brain's the loss of dopamine brain function, is involved is believed to result from .\lcohols and Ethers for normal is also involved in disease two neuronal path centers. Dopamine neurons along one of the reward and pleasure is producing in red responses. Dopamine dopamine, highlighted movement and emotional in the brain that rely on regulating ways other cells in the by the ending in its name. Neurons differ from most an amine, as suggested in Figure 7-61. so the loss ot regenerate themselves, II d in that they do n bo y with Parkinson's dis I anunc cells is permanent. Patients of these in this neuro N, percent less dopamine activity HO � 1-1 ease show 80 nal pathway. man� available to treat e prescription drugs are Effectiv pamine 1tsdl A/ inson's disease. Do of the symptoms of Park HO Dop�rmnc or Parkin• c for schizophrenia Although there is no ure are available to treat prescription drugs son's disease, In order to more debilitating symptoms. some of the and Parkin of schizophrenia tal -f understand the biochemistry cells Fron understand how nerve cortex son's disease, we must first on a molecular level. communicate with one another 11 100 billion (1 X 10 ) The human brain has about neurons communicate cells, known as neurons. Most nerve neurotransmitters: messengers known as through chemical functional characterized by an amine organic molecules with an between neurons begins group. Communication long • Dopamine pathway 1 travels along the axon, the electrical impulse that (in Parkinson's) electrical impulse reaches of a nerve cell. When the pathway 2 shaft are released from • Dopamine the end of the axon, neurotransmitters (in schizophrenia} between two ine.· the synaptic cleft, the gap ve dopam the neuron into • pathways that Invol ved ure 7-60. Neurotransmit ure 7-61 Neuronal nd is iovol in the inset in Fig Fig ovement a lS neurons, shown specific shown in red controls m eo affec where they bind to pathway shown in gre se to the next neuron, ase. The pathway href1il- ters diffu neuron. In Parkinson's dise in schizop membrane of the receiving tion and is involved receptors on the cell the memory, and motiva travel from one neuron to this way electrical impulses 13 • PRO 594 TEINS: STRUCTURE AND Fl.IN liit:i,Jl-1j®¢t§1tfAA1ACE Inhibitors as a Treatment for Hypertension Enzyme inhibitors have been used as pharmaceuticals in lungs the treatment of a wide angiorensin I, to produce range of diseases including cancer, the hormone angiotensin II, an AIDS, diabetes, and octapeptide, and the dipeptid heart disease. Some of the earliest e His-Leu. enzyme inhibitors were used Angiotensin II signals a number Liver before their mechanism of of physiological events action was even understood. that raise blood pressure: (1) Ltt \ Aspirin, for example, was Ir causes the muscles sur• used ro treat pain and rounding blood vessels to constrict-a inflammation long before it was process known as discovered in the l vasoconstriction, and (2) 970s to be an inhibitor 1 it triggers the release \J of C) c/o of the ste \.) ge11ase, a key oxy roid hormone aldosterone enzyme involved in several biochemical from the adrenal cortex, which 1 pathways leading signals the kidneys to reab . . , ACE . . to inflammation. sorb sodium ions rather than A 1 r
t1 11 1 A"GJ'c,lmsi11 Coi1vcl1i g E .:,•mc Asp-Arg-Val-Tyr-Ile-His-Pro- (ACI:.) Phe + His-Leu (Angiorcnsin II) Figure 13- The 31 key reactions and enzymes in the biochemical pathway renln-angiotensin that controls blood pressure. EnergyDrinks: Are They Really Harmless as a Source of Energy? - "·' AMINES -
Energy for use in the human body is provided by consuming and me shown that large quantities can cause s1gmficant II health behavioral eal'ti tabolizing carbohydrates, proteins, and fat.The energy content of such and problems. For ,,,/ instance. too muc tvo te consumed materials is usually given in units of calories. The primary can result in nervousness and insomnia. The tnso Alkaloids: Amines in "energy-providing" active ingredients in energy drinks are caffeine fatigue, leading to more caffeine consumption, mo�• Plants (1,3,7-trimethylxanthine, C8H 10N402) and sugar. Caffeine is an al more lack _of sleep, irritability, etc. Ad�itionuJly, inc Alkaloids Several alkaloids r� are physiologically are used in medicine. Quinine kaloid with no caloric value while sugar provides large amounts of consumption appears to correlate with an incre pounds produced active nitrogen-containing the bark of the cinchona obtained from ase in bo by plants. The alkaloid com tree has been used calories but no other nutrients. For this reason, energy provided by and occasionally, abnormal heart rhythms. 1 term refers malaria since in the treatment Add ctton t like or basic characteristics lo the alkali• the 1600s. Atropine from of sugar is often called "empty calories." In nature, caffeine is produced is possible, with unpleasant symptoms res we have seen for concentrations belladonna is used ulting upon °c alkaloids are used in anesthetics, amines. Certain to accelera1e unhealthy in low by plants such as Coffea arabica (coffee), Camellia sinensis (tea), of use. in antidepres anesthetic slow heart rates and lants, although many are sants, and as stimu for eye examinations. as an and Theobroma cacao (cocoa). The plants produce caffeine to pre Other implications associated with the co habit forming. nsumpl.lun of As a stimulant, nicotine vent insects and fungi from feeding on them. When animals, includ drinks areoften indirect. Lifeis full of tradeoffs and increases the level of energ) d blood, which increases adrenaline in the 3 ing humans, consume caffeine,it doesn't provide energy, but acts as no exception. When u person reachesfor an ene the heart rate and blood = CH rgy drink. thq known that smoking cigarettes pressure. ft is well CH, a stimulant which increases the heart rate and produces a temporary healthful beverages such us water, milk, or juice. can damage the lungs CH I Instead or sure to lars and other carcinogens and that expo boost in alertness. Sugar does provide energy, but it is in a short-lived ing water, calcium, vitamin D, or nutrients from the above-lhC lung cancer. in cigarette smoke can However, nicotine is responsible lead to � temporary form commonly referred to as a "sugar high." beverages, they are drinking an "energy" drink consisting smoking. Coniine, for the addiction HO which is oblained from oc of Caffeine has been consumed in many cultures forcenturies in the water and large quantities of caffeine and sugar. The excessne toxic alkaloid. heml k, is an extremely ;:b J� O CH,-OH form of tea and coffee, but something has changed. If you shop at gro consumption will have adverse long-term effects upon heal CH �111- cery or convenience stores, you cannot help noticing the large num example, high sugar diets are known to increase the risk of ber of energy drinks being promoted. These drinks come in brightly osteoporosis, and type 2 diabetes. CH,-w colored and even fluorescentcans displaying intense graphics to draw So. the next time you feel fatigued,drink a cool,ref re�hing 0-C6 Q attention. Whose attention are they trying to get? If you analyze the water and restfor a fewminutes. If you feel you must drinksom � nL3 CH,-CH,-CH, marketing strategies, the target audience consists of teenagers and to awaken the senses, try a cup of green tea without sugar. Tea g Qvi□inc young adults. tains no empty calories and provides antioxidants. Most im Nicollr.c A1ropinc Cooiinc So what is the big deal'! Although there is still plenty of debate remember that the best way to stay healthy and energized 1� to For many centuries, morphine and codeine, about caffeine and its effects on the body, empirical evidence has nutritious diet while getting plenty of rest and exercise. Caffeine the oriental poppy planl, have alkaloids found in is a stimulant of the central Codeine, been used as effective II coffee, tea, soft nervoussystem. Present which is structurally painkillers. drinks, chocolate, and in prescription similar to morphine, is used alertness,but may cocoa, caffeine increases painkillers and cough in some I cause nervousness and chemical syrups. Heroin, obtained used in certainpain to insomnia. Caffeineis also modificationof morphine, by a relievers counteract the used medically is strongly addicting and I an antihistamine. drowsiness caused by . is not I
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510 Chapter 16