Some of these questions are quite challenging. You may need to perform an intern

Question

Some of these questions are quite challenging. You may need to perform an internet search on these topics for more information. 1. Case 1: Pyruvate dehydrogenase complex (PDHC) deficiency This is a fairly rare genetic disorder. The enzyme that converts pyruvate to acetyl CoA is deficient. How will cell respiration be affected? What symptoms will be observed? For more information, perform an Internet search using “pyruvate dehydrogenase complex (PDHC) deficiency” as the search terms. 2. Case 2: Mitochondrial cytochrome b deficiency Cytochrome b is part of the electron transport chain in mitochondria. In this rare genetic disorder, only the mitochondria in the muscle are affected. Very early in their embryonic development, a mutation occurred in the cytochrome b gene in a cell destined to produce their muscles. How will cell respiration be affected? What symptoms will be observed? What will be observed during mild exercise? For more information, perform an Internet search using “mitochondrial cytochrome b deficiency” as the search terms. 3. Case 3: Thiamine deficiency Thiamine (vitamin B1) is an important cofactor in one of the reactions in the Krebs cycle, and also the reaction that converts pyruvate to acetyl CoA. It is normally found in the diet in yeast, pork, legumes, cereal grains, rice. It may become deficient during malnutrition or conditions that cause malnutrition such as alcoholism, HIV, and anorexia nervosa. How will cell respiration be affected? What symptoms will be observed? For more information, perform an Internet search using “thiamine deficiency” as the search terms. 4. Case 4: Electron transport chain inhibitors such as rotenone, antimycin, cyanide These inhibitors block one of the steps in the electron transport system. How will cell respiration be affected? What symptoms will be observed? For more information, perform an Internet search using “rotenone, antimycin, and cyanide” as search terms. 5. Case 5: Uncouplers such as 2, 4 Dinitrophenol An uncoupler allows hydrogen ions to leak back across the membrane. It uncouples the process of proton pumping with ATP production. How will cell respiration be affected? What symptoms will be observed? This drug was used in the 1930s as a weight-loss drug, but was banned in 1938 because of incidences of death. Why would weight loss occur? Why did some patients die? For more information, perform an Internet search using “uncouplers” as the search term. 6. Case 6: Oligomycin This drug is a direct inhibitor of ATP synthase in the electron transport system. How will cell respiration be affected? What symptoms will be observed? For more information, perform an Internet search using “oligomycin” as the search term.

Explanation / Answer

1)LDH deficiency-

limits production of citate because citrate is the 1st substrate,no further advancement can be noted.because of stoppage of cycle energy deficiency continues especiall in cells,magnitude of deficiet depends on residual activity of enzyme.reults in abnormal lactate build up in cells which leads to lactic acidosis.due to less clearence of lactic acid from the cell leads to oxygen deprivation,which results in tachyopnea.

LDH controls formation and regulation,uptake,synthesis,oxidationa and reuptake of lactate .avilable in 5 forms;

LDH 1,2 seen in heart and 3,4,5 seen in muscle.

symptoms include-nausea,vomiting,severe breathing problems,tachyopnea,abnormal heart beat,hypoxia.

2)cytochrome-b

cytochrome-b is the key component in mitochondria,as it is the power house of cell,needed for energy generation.

respiratory chain complex activities of comp1 and comp3 are markedly decreased.

the chemiosmosis is distrubed

and at the end there is drastic increase in lactic acid due to metabolic distrubances,

symptoms-muscle weakness(myopathy)

tiredness(fatigue),

tubulopathy,

brain dysfunction,

psycomotor delay,

hypotonia.

3)Thiamine deficiency in kreb's cycle-

it leads to distrubance in cellular respiration(enzymatic breakdown of glucose in presence of oxygen to produce energy)which results in distubances of yielding of energy.(ATP,NADH,FADH2)

Due to distrubance in cellular respiration there is starvation of cells which leads to hypoxia.

symptoms-

lethargy,

muscle weakness,

4)ETC inhibitors-

Rotenone is a neurotoxin,interfers with functioning of complex1 leads to impairment of mitochondrial complex,

which results in accumulation of free radical cells ultimately leads to cell death.

Antimycin A is produced by streptomyces griseus that used as pesticide.it interfers with electron flow from cytochrome bH in complex3.in the presence of antimycin A cytochrome bH can be reduced but not oxidized,consequently cytochrome c remains oxidized,as do the cytochromes a and a3 that are ahead.

cyanide intoxication inhibits the respiratory role,effects all metalloenzymes,but toxicity derives binding of Fe+3 in heme groups in cytochrome oxidase,inhits function of ETC.

Symptoms-

accumulation of toxic products due to incomplete fat oxidation.

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