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19 Jul 2019

Alcohol dehydrogenase (ADH) is mutated in alcoholics such as Ozzy Osbourne to facilitate alcohol consumption. What does ADH do and how is this possible? Also, be careful not to confuse alcohol dehydrogenase with antidiuretic hormone (also abbreviated ADH), which is also altered by alcohol consumption. Can you also describe how alcohol consumption alters antidiuretic hormone levels and how this results in a change in water retention?

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Hubert KochLv2

21 Jul 2019

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The people of Malaysia belong to three communities: the local people called Malays, immigrants from South India called Tamils, and immigrants from China. During the early 20th century, the Malays lived mainly in coastal villages, the Tamils worked on rubber estates, and the Chinese worked in tin mines. In general, the people were very poor and they consumed a limited variety of foods.[1] Rice was the staple diet of all three communities and therefore the key source of caloric and nutrient content. Malays typically grew their own rice and dehulled it before consuming it; dehulling partially removes the aleurone layer of the rice seed. Following their South Indian food habits, the Tamils ate parboiled rice, and the Chinese ate polished white rice imported from Thailand. It was found that among the three Malaysian communities, the Chinese community was much more prone to suffer from some degree of sub-optimal thiamin intake. Out of every 1,000 Chinese inhabitants, about 120 had mild thiamin deficiency, about 80 had severe thiamin deficiency, and about 16 people had died of it. Suboptimal intake of thiamin was rare in Malays and was not reported at all in Tamils.[1] Thiamin, also called Vitamin B1, is required for all tissues, and its deficiency causes the disease Beriberi. Less severe deficiency results in non-specific symptoms such as weight loss, malaise, irritability, and confusion. Although the origin of the word Beri-beri is disputed, it is believed to be a Philippine word meaning âI canât, I canâtâ and was probably coined to refer to the lack of neuromotor coordination in people afflicted with this disease.[2] Thiamin is water-soluble and is stable in the acidic medium. It is unstable to heat, oxygen, and UV light in neutral and alkaline medium. The active form of thiamin is thiamin pyrophosphate (TPP). This active form is a cofactor for pyruvate dehydrogenase and transketolase enzymes that are involved in the metabolism of carbohydrates. These enzymes play an important role in the biosynthesis of a number of cell constituents such as neurotransmitters, pentoses, and reduced equivalents, used in oxidant stress. The human body cannot store thiamin and therefore requires a continuous supply of the vitamin. The thiamin in an individual on a thiamin-free diet typically depletes in fewer than two weeks. Thiamin absorption is affected by compounds, called thiamin antagonists or anti-thiamin factors, that alter the structure of thiamin. These compounds include alcohols, polyphenols, flavonoids, and thiaminase, a heat labile enzyme found in certain foods.[2] In affluent countries, where the diet is rich in thiamin, the most common cause of thiamin deficiency is excessive alcohol consumption. Alcohol intake affects thiamin status in two ways. First, alcoholics get a significant percentage of their daily energy intake from alcoholic beverages, which are nutrient deficient. In other words, alcoholics replace their consumption of nutrient dense foods that are part of their normal diet with the consumption of nutrient deficient alcohol. Second, alcohol inhibits the intestinal ATPase involved in the absorption of thiamin.[4] Sub-clinical thiamin insufficiency associated with excessive alcohol consumption produces an encephalopathy called Wernicke-Korsafoff syndrome. Patients with this syndrome have a higher than normal incidence of abnormal transketolase, which has a very low binding affinity to TPP. This problem can be overcome by putting patients on high-dose thiamin therapy. Some patients, however, might have a form of abnormal transketolase that does not bind at all with TPP. Such people do not respond to high-dose thiamin therapy.[4] Thiamin deficiency is observed in individuals who have low thiamin intake and a diet rich in polished rice, especially if their diet also consists of anti-thiamin factors such as tea, coffee, raw fermented fish, and betel nuts. The minimum amount of thiamin needed by the body can increase because of increased physiological or metabolic demands arising from pregnancy and lactation, heavy physical exertion, illnesses like cancer, liver diseases, hyperthyroidism, and surgery. Since TPP is required for carbohydrate metabolism, the recommended dietary allowances for thiamin are based on the assumption that its intake is related to total energy intake. The recommended dietary allowance in the United States is 0.5 mg/1000 Kcal.

Questions
1. Thiamin deficiency was observed only in the Chinese community even though all three
communities had the same staple (rice) diet. Explain.
2. On packages of enriched rice sold in supermarkets, the rice preparation directions state that the
rice should not be washed before cooking. Explain.
3. Severe metabolic acidosis caused by high levels of lactate is often associated with thiamin
deficiency. Explain.
4. Provide two plausible explanations for what might cause above normal levels of pyruvate in blood
and urine. How can one determine which of the two explanations is correct?
5. Why does thiamin utilization increase among cancer patients?
6. A negative correlation exists between the need for thiamin and the amount of fat in the diet.
Explain.

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It took the diagnosis of high blood pressure (hypertension) at theage of 45 to shock Max into taking better care of himself. A formercollege football player, he had let himself go, eating too muchjunk food, drinking too much alcohol, sitting on his chubby bottomfor the majority of the last two decades, and even indulging in thefrequent habit of smoking cigars. Max's physician had to prescribetwo different antihypertensive medications in order to get hisblood pressure under control. She also prescribed regular exercise,a low-salt diet, modest alcohol intake, and smoking cessation. Maxwas scared, really scared. His father had hypertension at a youngage as well, and ended up on dialysis before dying fromcomplications of kidney failure.

Fortunately for Max, he took his doctor's advice and began adramatic lifestyle change that would bring him to his present-daysituation. Now, at the age of 55, he was a master triathlon athletewho routinely placed among the top five tri-athletes of the sameage group in the country. Max's competitive spirit had been ignitedby this, but at the same time he wanted to be first among hispeers. To that end, he hired Tracey, a Certified Clinical ExerciseSpecialist, to help him gain the edge he needed to win at the endof the race. His most immediate concern was that he wasexperiencing problems with dehydration and fatigue because hehadn't found an effective way to drink enough fluids whileexercising.

Tracey showed Max an impressive array of assessment tools forquantifying and analyzing his physiological state before, during,and after his workouts. One of the tools was urinalysis, which Maxfound a bit odd, but he dutifully supplied urine samples on aregular, prescribed basis. Tracey explained that Max's hydrationstatus was tricky due to the medication he took to control hishypertension, and that renal status (as measured in the urinalysis)was one of the tools she could use to evaluate his physiologicalstate. Tracey logs the following results of Max's urinalysisimmediately after, and six hours after, a rigorous 2-hour run.

Time	Color	SpecificGravity	Protein	Glucose	pH
Before exercise	pale yellow	1.002	absent	absent	6.0
Immediately afterexercise	dark yellow	1.035	small amount	absent	4.5
Six hours afterexercise	yellow	1.025	absent	small amount	5.0

Given the correlationbetween urine color and urine concentration, which of the followingstatements is true about Max's urine?

Given the correlation between urine color and urine concentration,which of the following statements is true about Max's urine?

	Max'surine is most concentrated before exercise.
	Max'surine is most dilute immediately post-exercise.
	Max'surine is least concentrated six hours post-exercise.
	Max'surine is most dilute before exercise.

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PartB

Max needs to drink morewater before exercise to avoid dehydration.

Max needs to drink more water before exercise to avoid dehydration.

	True
	False

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PartC

Antidiuretic hormone (ADH),which regulates urine concentration and dilution, is__________.

Antidiuretic hormone (ADH), which regulates urine concentration anddilution, is __________.

	highestsix hours after Max exercises
	highestbefore Max exercises
	lowestimmediately after Max exercises
	lowestbefore Max exercises

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PartD

Max is curious about theprotein content of his urine. Which of these statements provides anaccurate basis for Tracey's response, explaining normalconditions?

Max is curious about the protein content of his urine. Which ofthese statements provides an accurate basis for Tracey's response,explaining normal conditions?

	Mostproteins pass through the glomerular membrane and are present invarying amounts in urine.
	Fewproteins are small enough to pass through the glomerular membrane,but the few that do are reabsorbed. So, proteins are not usuallypresent in urine.
	Allproteins are negatively charged and too large to pass through theglomerular membrane. So, proteins are not normally present inurine.
	Mostproteins pass through the glomerular membrane and are reabsorbed.So, proteins are not present in urine.

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PartE

Tracey knows that the largepizza Max consumed just prior to collecting his third urine samplecaused a transient increase in his blood glucose levels. What canbe accurately said about the relationship between glucose in theblood and the amount of glucose filtered through the glomerularmembrane?

Tracey knows that the large pizza Max consumed just prior tocollecting his third urine sample caused a transient increase inhis blood glucose levels. What can be accurately said about therelationship between glucose in the blood and the amount of glucosefiltered through the glomerular membrane?

	Glucoserequires a transport protein to get through the glomerularmembrane, so glucose in the filtrate cannot increase even whenblood glucose concentration is high.
	Theglomerular membrane prevents glucose from entering the filtrateunless blood glucose concentration is abnormally high.
	Thehigher the blood glucose concentration, the more glucose isfiltered through the glomerular membrane.
	Onlysmall glucose molecules can filter through the glomerular membrane,but high blood glucose concentration increases the amount ofglucose in the filtrate.

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PartF

Tracey explains to Max thathis transiently elevated blood glucose leads to "spilling" ofglucose into his urine. Why does this happen?

Tracey explains to Max that his transiently elevated blood glucoseleads to "spilling" of glucose into his urine. Why does thishappen?

	Thetubule cells are unable to reabsorb any glucose that enters thefiltrate.
	Tubulecells inhibit glucose production when blood levels areelevated.
	Reabsorption of glucose is limited by transport proteins.
	Thetubule cells actively secrete excess glucose into thefiltrate.

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PartG

During strenuous exercise,Max's body produces lactic acid and his blood pH begins to decline.His kidneys go to work to preserve acid-base balance by doing allof the following EXCEPT __________.

During strenuous exercise, Max's body produces lactic acid and hisblood pH begins to decline. His kidneys go to work to preserveacid-base balance by doing all of the following EXCEPT __________.

	generating new bicarbonate
	reabsorbing bicarbonate
	secretinghydrogen
	reabsorbing hydrogen

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PartH

What does the color ofMax's urine tell Tracey about how concentrated or dilute it is? Howdoes Max's urine color/concentration compare to the urine specificgravity at the same time?

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PartI

Based on the urine colorand specific gravity, what might Tracey conclude about thehydration status of Max's body at the three different times?

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PartJ

Antidiuretic hormone (ADH)regulates the formation of concentrated or dilute urine. In whichtime period is Max's body secreting its highest amount of ADH?Explain your answer.

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PartK

Tracey knows thatproteinuria (protein in the urine) after intense exercise isphysiological (normal). However, protein is typically not presentin urine. Why is that?

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PartL

Tracey had been slightlyconcerned about the trace glucose that was found in Max's urine sixhours after his exercise until she discovered that he had eaten anentire large pizza an hour before the urinalysis. Explain whyglucose might show up in Max's urine after a particularly heavymeal.

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PartM

Lactic acid accumulationcan be a consequence of intense exercise. Tracey notes that Max'skidneys are working to defend his body against acidosis. How canshe tell? Describe this mechanism.

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PartN

Based on Max's urinalysisdata, should he drink more water prior to exercise to ensure thathe doesn't dehydrate during intense activity? Explain youranswer.

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PartO

Max's regular exerciseregimen has reduced his high blood pressure, allowing him toachieve normal blood pressure on a single antihypertensivemedication. The medication he takes is called an angiotensinconverting enzyme inhibitor, or ACE inhibitor, which blocks theactivation of angiotensin II. Describe at least two mechanisms bywhich angiotensin II targets the kidneys to increase extracellularfluid volume and, therefore, increase blood pressure.

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ceruleansheep578

4. In addition to their use in motility, flagella can also be used to sense when the bacterial cell comes in contact with a surface.

A. How are flagella used in motility? How does a bacterium move toward a nutrient source using flagella?

B. Now itâs time to think at the molecular size and do some visualization. Youâre standing on a bacterial cell membrane watching ions flow and flagella turn. All of a sudden, the cell runs into a surface, and the flagella stop turning. What will happen (immediately) to the PMF? Describe two ways the cell (in the next few moments) could compensate for this? As the cell compensates, how will its oxygen consumption be altered? Its ATP production?

C. Instead of the compensations you mentioned above, some bacteria have the ability to produce a special protein that acts to increase the distance between the flagellar rotor and stator so that this distance is much larger than a hydrogen ion. Explain how this protein will affect the PMF and the rotation of the flagella.