BIOCHEMISTRY 520

EXAM 3

October 2, 1998

PART I.  (60 points)

Each of the following statements is followed by five suggested answers or
completions.  ON THE ANSWER SHEET, mark the one which is best in each
case.

1.	Which of the following compounds generally accumulates in the
	urine in folic acid deficiency?    
	A.	methionine
	B.	methylmalonic acid
	C.	branch chain alpha-keto acids
	D.	homogentisic acid
	E.	N-formiminoglutamate (FIGLU)

2.	Ammonium ion in the urine arises primarily from   
	A. 	the action of glutamate dehydrogenase in the kidney.
	B. 	the action of kidney glutaminase upon the side-chain amide of blood 
		glutamine.
	C.	the direct action of aminotransferases
	D.	the action of kidney glutaminase on the alpha-amino group
		of glutamine.
	E.	metabolism of uracil.
                                                                              
3.	Thioredoxin is a protein required  for the synthesis of    
	A.	ADP.
	B.	inosinic acid.
	C.	dADP.
	D.	carbamoyl phosphate.
	E.	5-phosphoribosyl-1-pyrophosphate.

4.	Which of the following excretion products would be increased to
	the largest extent after the ingestion of a 12 ounce steak by a human?    
	A.	Uric acid
	B.	Urea
	C.	Asparagine
	D.	Ammonia
	E.	Creatine

5.	A deficiency in which of the following amino acids would result in
	a Negative Nitrogen Balance?
	A.	Serine
	B.	Cysteine
	C.	Proline
	D.	Tryptophan
	E. 	Asparagine

6. 	In PKU, Maple Syrup Urine Disease (MSUD), and genetic defects in the
	urea cycle it is important to avoid periods of fasting because:

	A.	Fasting makes you deficient in ATP
	B.	Fasting causes ketoacidosis
	C.	Fasting causes muscle protein catabolism
	D.	Fasting stimulates gluconeogenesis
	E. 	Fasting causes gout

7. 	The toxicity of  NH3 may be due to depletion of this citric acid cycle
	intermediate 
     	A.  	alpha-ketoglutarate
	B.	Citric acid
	C.	Oxaloacetate
	D.	Succinate
	E.	Fumarate

8. 	What is believed to be the major biochemical consequence in the normal
	individual of LDL uptake by extrahepatic tissues?
	A.	HMG-CoA Reductase is activated
	B.	Cholesterol synthesis is suppressed in these tissues.
	C.	Uptake of HDL particles is suppressed.
	D.	Lipolysis is stimulated in these tissues.
	E.	Atherosclerosis is reversed.

9. 	Which of the following represents a step that is common to the
	digestion of fat, glycogen and proteins?
	A.	All require hydrolysis reactions in the small intestine
		before uptake by mucosal cells.
	B.	All require a Na+ gradient for uptake into the mucosal
		cell
	C.	All involve resynthesis in the mucosal cell before
		entering the blood
	D.	All pass directly from the mucosal cell into the blood
	E.	All are directed from the mucosal cells to the liver
		before encountering other tissues

10. 	A positive  nitrogen balance is observed in which of the following
	conditions?
	A.	obesity
	B.	pregnancy
	C.	menstruation
	D.	moderate exercise
	E.	sleep

11. 	VLDL transports primarily
	A.	exogenous cholesterol esters.
	B.	endogenous triglycerides.
	C.	exogenous triglycerides.
	D.	endogenous cholesterol esters.
	E.	apolipoproteins

12.	The apolipoprotein important for the activation of lipoprotein
	lipase is:
	A.	Apo A1
	B.	Apo B48
	C.	Apo B100
	D.	Apo CII
	E.	Apo E

13.	The Lesch-Nyhan Syndrome is an inherited disorder associated with
	a virtually complete deficiency of an enzyme of purine metabolism, which
	is   
	A.	adenylosuccinate lyase.
	B.	aspartate carbamoyl transferase.
	C.	hypoxanthine-guanine phosphoribosyl transferase.
	D.	purine nucleotide phosphorylase.
	E.	xanthine oxidase.

14.	The liver is capable of all of the following EXCEPT:
	A.	Urea synthesis
	B.	Gluconeogenesis from glycerol
	C.	Synthesis of bile salts
	D.	Oxidation of acetoacetate
	E.	VLDL synthesis

15.	PKU patients are characterized by all of the following EXCEPT:
	A.	Elevated levels of phenylalanine
	B.	Elevated levels of phenyl lactate and phenyl acetate
	C.	Hyperpigmentation (dark skin)
	D.	Tyrosine becomes an essential amino acid
	E.	Need for a phenylalanine-deficient diet for life

16. 	Caffeine has a purine ring  in which each of three nitrogen atoms
	bears a methyl group.  The most direct precursor (i.e., requiring fewest
	reactions) of these methyl groups is
	A.	a methyl derivative of tetrahydrofolic acid.
	B.	S-adenosyl-methionine.
	C.	trimethylglycine.
	D.	homocysteine.
	E.	creatine phosphate.

17.	Compounds derived from HMG-CoA (b-hydroxy-b-methyl-glutaryl CoA)
	include all of the following EXCEPT:
 	A. 	Male steroid hormones
	B.	Cholesterol
	C.	Bile acids
	D.	Glucose
	E.	Ketone bodies
	
18.	The principal nitrogenous urinary excretion product in humans
	resulting from the catabolism of AMP is:
	A.	Creatinine
	B.	Urea
	C.	Uric acid
	D.	NH4+
	E.	Orotic acid

19.	Compared to a healthy person, a person with pernicious anemia
	A.	Produces less intrinsic factor
	B.	Excretes less methylmalonic acid in the urine
	C.	Requires less methionine in the diet
	D.	Has a higher rate of purine biosynthesis
	E.	Has lower blood levels of FIGLU
	
20.	Which compound mediates most of the transfer reactions involving
	the Aone-carbon@ pool in multiple oxidation states?
	A.	S-adenosyl methionine
	B.	Pyridoxal phosphate
	C.	Tetrahydrofolate
	D.	Vitamin E
	E.	Biotin

21.	The nucleotide that is used to activate choline for transfer to
	1,2-diacylglycerol for lecithin synthesis is:
	A.	ATP
	B.	GTP
	C.	CTP
	D.	UTP
	E.	TTP

22.	The antitumor reagent methotrexate functions by
	A.	Directly inhibiting the enzyme dihydrofolate reductase
	B.	Inhibiting synthesis of folate
	C.	Directly inhibiting the enzyme thymidylate synthase
	D.	Blocking absorption of vitamin B12
	E.	Inhibiting oxidation of folic acid

23.	An infant presents with symptoms of Maple Syrup Urine disease.  If
	the defect involved a mutation resulting in an increased Km of the
	defective enzyme for its coenzyme, which of the following vitamins in
	megadoses might help?
	A.	Vitamin B12
	B.	Folic acid
	C.	Biotin
	D.	Thiamine
	E.	Vitamin B6

24.	Respiratory distress syndrome in premature newborns is caused by
	deficiency in the lungs of:
	A.	Sphingomyelin
	B.	Gangliosides
	C.	Triacylglycerols
	D.	Phosphatidylcholine
	E.	Prostaglandins

25.	Diabetes mellitus could be caused by
	A.	Insufficient secretion of insulin
	B.	Antibodies to pancreatic b-cells (autoimmune disease)
	C.	Glucokinase mutation
	D.	Ineffective insulin receptors
	E.	All of the above

26.	Compounds derived from phenylalanine include all of the following
	EXCEPT:
	A.	Tyrosine
	B.	Thyroid hormones T3 and T4
	C.	Melanin (skin pigment)
	D.	Epinephrine
	E.	Serotonin

27.	The decarboxylation reactions necessary to synthesize epinephrine,
	GABA, serotonin and histamine require the cofactor:
	A.	Pyridoxal phosphate
	B.	Thiamine pyrophosphate
	C.	Biotin
	D.	NAD+
	E.	Tetrahydrofolate

28.	Familial hypercholesterolemia is caused by
	A.	Defective lipoprotein lipase
	B.	Defective ACAT
	C.	Defective HMG-CoA reductase
	D.	Defective LDL receptors
	E.	Defective HDL particles

29.	The end product of purine metabolism in a person taking
	allopurinol for gout is
	A.	Orotic acid
	B.	Hypoxanthine
	C.	Urate
	D.	dTMP
	E.	GMP

30.	Which of the following would NOT be characteristic of most
	sphingolipid storage diseases, such as Tay-Sachs and Gauchers disease?
	A.	A genetic defect
	B.	A deficiency of a hydrolytic enzyme (hydrolase) in
		lysosomes
	C.	An unaffected  synthetic pathway for the sphingolipid
	D.	An accumulation of the sphingolipid in lysosomes
	E.	A relatively benign disease with only mild arthritis
		developing in old age

	
 
	BIOCHEMISTRY 520
	Examination #3 - October 2, 1998



NAME___________________________________

PART II.  (40 points)

I.	(7 points)   A 6-year-old girl was brought to the hospital with
vision problems.  She was found to have a downward dislocation of the left
lens.  Her mother indicated that the girl=s birth was normal but that she
lagged in development.  She was unable to crawl until she was 1 year old
and did not walk until she was 2 years old.  Speaking was also delayed.
She had long, thin bones; x-rays of the lower femur showed signs of
osteoporosis.  An older brother had similar symptoms but had been
diagnosed as having Marfan=s syndrome.  A simple cyanide-nitroprusside
test of the patient's urine was positive, suggesting homocystinuria, not
Marfan=s syndrome.  This was confirmed by amino acid analysis of the
plasma, which revealed homocystine, an abnormally high methionine level,
and other derivatives of homocysteine.  The patient was treated with a
low-methionine diet supplemented with folic acid and pyridoxine (vit. B6).

	A.	What is the origin of the homocystine excreted in this
		disease?  Show how it is produced.








	B.	What is the rationale for treating the patient with:

		1. pyridoxine






		2. folic acid




	C.	What other vitamin might be useful to administer?




	D.	Elevated blood levels of homocysteine have been associated
		with what other relatively common killer disease?





II.	(6 points)  A 15-year-old boy had a long history of abdominal
complaints, including bouts of abdominal pain so severe that narcotics
were required for relief.  These episodes were intermittent, occurring
about every 6 months.  On one occasion abdominal surgery (an exploratory
laparotomy) was performed, and the patient's appendix was removed.
However, this did not correct the problem.  The patient had recently felt
well until he suddenly developed another episode of abdominal pain.  His
mother stated that the illness came on shortly after he had eaten a fatty
meal.  No one else in the family had been made ill by this meal.  The
patient was brought to the hospital at 8:00 AM, 14 hours after his last
meal.  On arrival, a blood specimen was drawn.  Within 15 minutes the
laboratory technician reported that valid results could not be obtained
from the blood plasma because it was Amilky.@  After centrifugation for 30
minutes at 15,000 RPM, the plasma cleared considerably, and there was a
thick band of Acream@ located at the top of the specimen.

	A.	What kind of lipid abnormality would you suspect in this
patient?  Be as specific as you can.




	B.	Assuming this is a genetic disease, what protein or enzyme
could be defective?  What is its normal role in metabolism?



	C.	A low fat diet was recommended, supplemented with medium
chain fatty acids having 6-10 carbons (MCFA).  How will MCFA help this
patient?





	D.	(2 points extra credit) What kind of studies would you
perform on blood samples to confirm your diagnosis in part B?  Be as
specific as you can.






 III.	(5 points) Identify the labeled components (A-D) in the diagram
below.

		(FIGURE 20.3 FROM TEXT)
		

	A.	___________________________________
	
	B.	______________________________
	
	C.	______________________________
	
	D.	______________________________
	
	E.	What is the function of lecithin (phosphatidylcholine) in
		this pathway?
	




IV.	(10 points) For the boxes in the diagram below, identify an amino
acid that would be metabolized according to the diagram.  Three letter
abbreviations for the amino acids are sufficient.  You may only use an
amino acid ONCE in completing this question.  Answer any 10 out of the 13
blanks (A-M).  If you answer more than 10, the first 10 you answer will be
graded.
(FIGURE 39.2 IN MARKS, MARKS AND SMITH, SHOWING PYRUVATE, ACETYL
COA, ACETOACETATE AND CITRIC ACID CYCLE, WITH ARROWS REPRESENTING ENTRY
POINTS FOR VARIOUS AMINO ACIDS)


A.____________________________
					H.__________________________________ 

B.____________________________
					I.__________________________________

C.____________________________
					J.__________________________________

D.____________________________
					K._________________________________

E.____________________________
					L.__________________________________

F.____________________________
					M._________________________________

G.____________________________
  



V.	(8 points) Distinguish between the following pairs of
molecules/complexes.  Explain how they differ and what their role is.
	A.	ACAT and LCAT





	B.	Pancreatic lipase and lipoprotein lipase





	C.	Glutamate dehydrogenase and glutaminase





	D.	Carbamoyl phosphate synthetases I and II





VI. (4 points) Identify the following structures

	(1) URIC ACID	(2)  GLYCOCHOLIC ACID	(3)  UREA	(4)  PRPP