Biochem 385 Exam 3

15N-labeled aspartate is provided to bacteria during the biosynthesis of pyrimidine trinucleotides. The radiolabeled nitrogen would ultimately be found in

both UTP and CTP

Which metabolite is an intermediate in both pyrimidine biosynthesis and the urea cycle?

carbamoyl phosphate

Which of the following is labeled 3 in the figure below?

citrulline

In the duodenum, enteropeptidase:

cleaves trypsinogen to form trypsin.

There are many diseases collectively called porphyrias that are characterized by the accumulation of heme precursors in the blood and liver. Which type of porphyria is characterized by low uroporphyrinogen III synthesis?

congenital erythropoietic porphyria

Inhibition of the COX-1 enzyme results in

reduced mucin secretion in the stomach

Orlistat and olestra can both lead to undigested lipids in the colon, yet they do so by contrasting mechanisms. Orlistat ________, whereas olestra ________.

inhibits pancreatic lipase; is a fat substitute that is not a substitute for pancreatic lipase

Dihydropyrimidine dehydrogenase deficiencies can lead to toxic side effects from high doses of 5-fluorouracil because 5-fluorouracil __________ dihydropyrimidine dehydrogenase.

is degraded by

Glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal cells in response to nutrientdetection in the small intestine. The resulting physiological response is the lowering of blood glucose levels.Which of the following is a potential mechanism for how GLP-1 signaling leads to lower blood glucose?

stimulation of insulin release by pancreatic beta cells

Glucagon-like peptide-1 (GLP-1) is a hormone peptide secreted by intestinal L cells. It is secreted in response to the nutrient detection in the small intestine. The resulting physiological response is the lowering of blood glucose levels. Which of the following is a potential mechanism for how GLP-1 causes this physiological response?

stimulation of insulin release by pancreatic-beta cells

What molecule is the odd chain fatty acid product propionyl-CoA converted into?

succinylcholine-CoA

Ubiquitination is most often regulated by biochemicalmodifications to which two types of proteins (choices at the right):

target proteins and E3 ligases

What would happen if purified leptin protein were injected daily into the db/db (diabetes) mouse as compared to a littermate db/db mouse that did not get leptin injections?

the mouse with leptin would be as fat as the mouse without leptin

Which of the following do- oxidation and fatty acid synthesis have in common?

the presence of an oxidized fatty acyl-carbon with a hydroxyl or carbonyl group as a pathway intermediate

How does biological fixation convert nitrogen to ammonia?

through the ATP-dependent process catalyzed by nitrogenase complex

Partial hydrogenation can result in the formation of

trans double bonds

In the figure below of the E. coli ribonucleotide reductase enzyme, which amino acid is important in the R2 subunit?

tyrosine

Which pathway does NOT provide metabolic precursors for amino acid synthesis?

urea cycle (pentose phosphate pathway, citrate cycle, and glycolysis are precursors)

Which of the following is NOT a major type of plasma membrane lipid?

wax

If an alteration occurred in the activity site of the R1 subunit of E. coliribonucleotide reductase that allowed dATP to bind but precluded ATP binding to the site, a possible result would be that ribonucleotide reductase

would be decreased when dATP bound both the activity and specificity sites.

A variety of energy stores are available for ATP production during exercise. Rank these fuel sources in the order that they would be used in the muscle during a long run (i.e., 10 K or more).

1 - muscle ATP2 - muscle phosphocreatine3 - muscle glycogen4 - fatty acids from adipose tissue

What is the biochemical explanation for why rapid weight loss is reported with protein-rich diets?

Amino acid degradation results in urea production to remove excess NH4+, so mostly water weight loss.

Nucleotides such as ATP shown at the righthave four key roles in biochemical processes. Name TWOof the possible four.

Coenzyme-dependent reactions and energy conversion.

Which of the following is correct concerning ribonucleotide reductase?

Ribonucleotide reductase in most eukaryotes contains a dinuclear Fe3+ center in the R2 subunit.

On exposure to insulin, the liver responds by upregulating __________, which in turn causes the upregulation of __________.

protein phosphatase 2A; acetyl-CoA carboxylase

Why is it a bad idea to eat a Fun Size bag of Skittles (205 grams) 10 minutes before a halfmarathon (13.1 miles)? Note the ingredients in a bag of Skittles shown in the box to the right:

Carbohydrate will cause an increase in insulin and inhibit fatty acid oxidationlater in the race, which will decrease available metabolic energy.

Thrifty genes are ________ during times of starvation and ________ when physical activity is low.

beneficial; detrimental

Which of the following is the product of uracil degradation?

beta-alanine

Leptin is an adipocyte hormone that send signals to the brain to "eat less" and "metabolize more." What is the explanation for why leptin injections cause weight loss in the strain of ob/ob mutant mice, but leptin injections has no effect in the majority of people?

ob/ob mutant mice lack leptin, and by providing it through injection, they are able to better maintain energy balance and metabolic homeostasis. In contrast, obese humans have chronically high leptin levels and are in fact leptin-insensitive.

What is the explanation for why leptin injections cause weight loss in the strain of ob/ob mutantmice, but leptin injections has no effect in the majority of people?

ob/ob mutant mice lack leptin, and by providing it through injection, they are able to better maintainenergy balance and metabolic homeostasis. In contrast, obese humans have chronically high leptinlevels and are often leptin-insensitive.

A person who has alkaptonuria is easily diagnosed from their black urine. What causes the black color?

oxidation of homogentisate

What two pathways provide the ATP needed to phosphorylate creatine during muscle contraction?

oxidative phosphorylation and glycolysis

The conversion of ribose-1-phosphate to guanosine-5'-triphosphate via the salvage pathway would require the activity of several enzymes. Choose the answer that lists them in the order that they would act in this pathway.

phosphopentomutase --> PRPP synthetase --> phosphoribosyl transferase --> kinase --> kinase

The conversion of ribose-1-phosphate to ATP via the salvage pathway would require the activity of several enzymes. Choose the answer that lists them in the order that they would act in this pathway.

phosphopentomutase; PRPP synthetase; phosphoriboxyl transferase; kinase; kinase

Elevated serum levels of free fatty acids prevents the

phosphorylation of tyrosine in insulin receptor substrate 1 protein.

Diseases affecting heme biosynthesis as a result of deficiencies in the heme biosynthetic pathway are called _________.

porphyria

Sort the amino acids as to whether they are considered essential or nonessential amino acids in humans.

-Essential: valine, threonin, lysine -Nonessential: glycine, cysteine

What two nucleic acid bases are represented by the structures (1) and (2) shown below?

1 - cytosine2 - uracil

How does depletion of liver glycogen stores during starvation lead to a shift from glucose utilization to fatty acid oxidation as an energy source for most tissues?

-Glucagon activates hormone-sensitive lipase.-Lack of liver glycogen stores results in a drop in serum glucose concentration.-Lack of insulin signaling reduces GLUT4 translocation.

How does the cell regulate the substrate specificity of ribonucleotide reductase to maintain equal amounts of all four deoxynucleoside triphosphates (dNTPs)?

-When dTTP is bound to the specificity site, more dGDP is produced.-When dGTP is bound to the specificity site, more dADP is produced.

Which of the following are regulatory mechanisms that exist to prevent futile cycling in lipid metabolism?

-citrate activation of acetyl-CoA carboxylase -malonyl-CoA inhibition of CPT1 -AMPK phosphorylation of acetyl-CoA carboxylase -fatty acyl-CoA inhibition of acetyl-CoA carboxylase

Sort the descriptions below to indicate whether they describe β oxidation of stearoyl-CoA, oleoyl-CoA, or both.

-Stearoyl-CoA: 8 FAD reduced -Oleoyl-CoA: 7 FAD reduced; requires enol-CoA -Both: 8 NAD+ reduced; beta-oxidation completed in 8 rounds; 9 acetyl-CoA produced

Which two statements below accurately describe the roles of insulin and glucagon in maintaining metabolic homeostasis?

-insulin stimulates glucose uptake in muscle cells-glucagon increases blood glucose levels in between meals

Phenylketonuria is caused by a defect in the enzyme phenylalanine hydroxylase (1) /phenylalanine aminotransferase (2). The symptoms of the disorder are caused by substrate accumulation(3) / lack of product (4) and can be treated by diet which limits phenylalanine (5) / tyrosine (6). Albinism ischaracterized by white skin and hair due to a defect in the enzyme arginase (7) / tyrosinase (8) and ischaracterized by a substrate accumulation (9) / lack of product (10) mechanism.

1, 3, 5, 8, 10

The thymidylate synthase reaction is a linear pathway in E. coli that leads to dTTP production. Rank the following in order of enzymatic activity from earlier to later in the linear pathway of dUTP conversion to dTTP.

1. dUTP diphosphohydrolase2. Thymidylate synthase3. thymidylate kinase4. nucleoside diphosphate kinase

The conversion of 7-dehydrocholesterol to 1,25-hydroxyvitamin D3 involves all of the following except

11B-hydroxylase

A) Which of the following is correct and most accurately describes the complete urea cycle of the eukaryotic cell? B) Which cellular change(s) would not encourage the Krebs bicycle and thus the probability of the urea cycle taking place to completion?

A) The urea cycle occurs between the mitochondrial matrix and the cytoplasm of the eukaryotic cell. B) Increased conversion of oxaloacetate into citrate; increased aspartate charging to mitochondrial tRNAs

A) Within the image, identify the components of proteasomal degradation of a biomolecule. Drag the names of the components and/or features to their appropriate targets. B) Other than the proteasome, there is a second organelle mechanism of protein degradation within the eukaryotic cell. Which of the following organelles is also involved in protein degradation?

A) Ub. tag --> condemned protein --> gated pore --> protease active site B) lysosome

A) Upon deamination of an amino acid, which component becomes substrate for the urea cycle? B) In a eukaryotic cell, deamination of amino acids takes place most extensively in the_______. C) Within the urea cycle, citrulline is produced by ornithine transcarbmylase in the __________ and is consumed in the_________.

A) ammonia B) mitochondrial matrix C) mitochondria; cytoplasm

A) In this molecular structure, thymidylate synthase is shown associating with which of the following?B) There are ___α helices that comprise the secondary structures of thymidylate synthase, and ___ of these α helices comprise the active site of thymidylate synthase. C) Considering the physiology of thymidylate synthase, why is Tomudex an effective anticancer drug?

A) dUMP and raltitrexedB) eight; someC) The drug is a noncompetitive inhibitor that binds to thymidylate synthase and decreases enzymatic activity. This causes an imbalance in the quantities of dNTPs that are available for DNA replication.

A) Which catecholamine is made by the action of tyrosine hydroxylase and aromatic amino acid decarboxylase? (Assume that a biologically relevant molarity of all substrates for both tyrosine hydroxylase and aromatic amino acid decarboxylase are available.)B) Consider the following scenario. Dopamine ß-hydroxylase and phenylethanolamine N-methyltransferase participate in a linear biochemical cascade. Sort the following chemicals into their appropriate bins in terms of their relevance to the reaction cascade that involves dopamine ß-hydroxylase and phenylethanolamine N-methyltransferase enzymatic activity.

A) dopamineB) reactant = dopamine; intermediate = norepinephrine; product = epinephrine; n/a = dopaquinone

A) Isolate one polypeptide subunit of the ubiquitin structure by clicking the black-outlined box for "a (amino)" or "b (amino)" on the bottom of the player screen. This will either display or remove them from view. Observe the ribbon structure.B) When observing both ubiquitin polypeptides in this molecular structure that are covalently bonded together, the covalent bond that leads to polyubiquitination is a bond between which two residues?C) After covalent modification of a target protein with the ubiquitin that is shown in the molecular structure, what is the most likely fate of the ubiquitin chain?

A)parallel β sheetsB) lysine and glycineC) The target protein, without the polyubiquitin attachment, will be accepted into the proteasome and digested; ATP will be consumed during this process. The ubiquitin concentration in the cytoplasm will remain stable.

A) What purine metabolite is the likely cause of gout?B) Why was gout associated with ethanol and meat consumption?C) In humans, allopurinol can be used as treatment for gout because this drug is a competitive inhibitor of

A)uric acidB)ethanol interferes with excretion of purine breakdown chemicals and some foods contain high levels of purinesC) xanthine oxidase

Individuals with type 2 diabetes are often prescribed the drug, Metformin, which activates AMPKsignaling. Why would Metformin be an effective treatment for obese individuals with type 2 diabetes?

AMPK increases glycolytic flux and increases fatty acid oxidation, resulting in burning of fat stores as well as increased cellular glucose uptake.

What precursors are required for the beta-oxidation of palmitate?

ATP and oA

ADA-SCID is caused by mutations in the enzyme adenosine deaminase leading to accumulationof deoxyadenosine (dA). Excess dA increases production of dATP and inhibition of DNA replication indeveloping immune cells, causing the SCID immunodeficiency phenotype. Which combination of allostericeffectors bound to the specificity site and the activity site of ribonucleotide reductase provides the BESTbiochemical explanation for the ADA-SCID phenotype?

ATP bound to the specificity site; dATP bound to the activity site of ribonucleotide reductase.

Regulation of aspartate transcarbamoylase (ATCase) by nucleotides controls flux through the pyrimidine biosynthetic pathway in bacteria. Choose the two true statements below that describe this regulation.

ATP is an allosteric activator of ATCase activity; CTP is an allosteric inhibitor of ATCase activity

Leptin secretion from adipocytes is associated with too much stored fat. Leptin binding to POMC neurons causes which of the following effects?

Activation of anorexigenic neurons, resulting in decreased appetite and increased energy expenditure. Fat storage isinhibited.

Aspartate transcarbamoylase (ACTase) is a ratelimitingenzyme in the pyrimidine biosynthetic pathway of bacteria.How is ACTase allosterically-regulated in bacterial cells?

CTP shifts ATCase to the T state

Why is ingesting large amounts of L-arginine a viable treatment for argininosuccinase deficiency?

Arginine is converted to ornithine, which provides urea cycle intermediates needed for nitrogen removal.

Why does it makes sense that ghrelin stimulates orexigenic neurons (eat more/metabolize less)?

Because ghrelin is released from stomach cells when your stomach is empty.

Statin drugs can cause severe side effects in some individuals (debilitating muscle pain) and alternative treatments need to be used to lower their serum cholesterol levels. Name the two most common treatments and describe how they lower cholesterol levels.

Bile acid resins reduce cholesterol via higher bile acid synthesis; ezetimibe to block dietary cholesterol

Which of the following does NOT occur during starvation?

Brain cells begin using fatty acids as an energy source.

Explain how a deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD) could lead tosevere side effects in cancer treatments using 5-fluorouracil (5-FU) as a chemotherapeutic agent.

DPD degrades 5-FU so high doses need to be given, if DPD is deficient, then high 5-FU doses are toxic.

Which of these three diets below is the most incomplete with regard to nutrition and why?Diet 1: carbohydrate + lipidDiet 2: protein + carbohydratesDiet 3: amino acids + fatty acids

Diet 1; because it lacks protein, which provides 10 essential amino acids required for protein synthesis

Which of the three proteins in the ubiquination pathway is the most responsible for recognizing the ubiquintated target protein?

E3

Which of the following is a coenzyme that is derived from ATP?

FAD

In the Krebs bicycle, which of the following citrate cycle intermediates links to the urea cycle via argininosuccinate?

Fumarate (Explaination: the Krebs bicycle allowas for fumerate from the citrate cycle to be used to make aspartate, which is then combines with citruline to make argininosuccinate, a substrate in the Urea cycle. Argininosuccinate is broken down into arginine, which continues in the urea cycle, and fumarate, which is converted back into malate for transport and use in the citrate cycle)

Insulin signals for an increase in glucose uptake in both skeletal muscle and adipose tissue. Which of the following correctly describes how these organs use this glucose?

Glucose in muscle cells is completely oxidized or stored as glycogen, depending on the ATP demand. In adipose tissue, glucose is used to synthesize fatty acids and glycerol.

AMP-dependent protein kinase (AMPK) is activated by low energy charge (higher AMP) andphosphorylates downstream target proteins, some of which are inhibited by phosphorylation. Inhibition ofwhich two enzymes by AMPK phosphorylation will result in an increased energy charge (higher ATP)?

Glycogen synthase and acetyl-CoA carboxylase

Which of the following statements correctly describes an interaction between the ATP and GTP biosynthetic pathways?

Greater ATP production will positively regulate GTP synthesis because ATP is involved in the conversion of xanthosine-5'-monophosphate into guanosine-5'-monophosphate.

Why is de novo biosynthesis of purines markedly elevated in patients with a deficiency inhypoxanthine-guanine phosphoribosyl transferase (HGPRT)?

HGPRT deficiency prevents purine salvage, leading to increased purine biosynthesis to make up for it.

Which enzyme catalyzes the rate-limiting step of cholesterol synthesis?

HMG-CoA reductase

How do statin drugs function to reduce the risk of cardiovascular disease?

Inhibit HMG-CoA reductase to reduce cholesterol synthesis and increase LDL receptor synthesis

What explains the smell of acetone on the breath of dieters following the Atkins diet?

Insufficient carbohydrates to maintain flux through the citrate cycle leads to increased ketogenesis.

How does the herbicide, glyphosate, work?

It inhibits the shikimate pathway, preventing production of phenylalanine, tyrosine, and tryptophan.

Why does glucagon signaling stimulate glucose and fatty acid release from liver and adiposetissue, but has no effect on muscle cells even though muscle cells contain glycogen?

Muscle lacks glucose-6-phosphatase, contains insulin receptors, and lacks glucagon receptors

Which of the following is the net reaction of the urea cycle?

NH+ + HCO3 + aspartate + 3ATP urea + fumerate + 2 ADP + 2Pi + AMP + PPi

Nitric Oxide (NO) is a soluble gas and regulator of intracellular pathways causing vasodilation.What is the mechanism by which NO reduces blood pressure by stimulating vasodilation?

NO binds to guanylate cyclase to stimulate cyclic GMP production, which leads to vasodilation.

Undiagnosed phenylketonuria (PKU) can lead to severe neuronal damage and mental incapacity, which is avoidable if the disease is diagnosed at birth. In contrast, albinism is easly diagnosed at birth, but there is no treatment, which leads to an increased risk of skin cancer in these patients. Choose the three statements that BEST explain the reasons for these differences.

PKU is the result of substrate accumulation, which can be avoided using a restricted diet. However, albinism is due to a missing product, which cannot be replaced through injections or dietary regimens.-Defects in the enzyme tyrosinase occur in every cell of the body and there is no way to replace this enzyme without embryonic human gene therapy. In contrast, defects in the enzyme phenylalanine hydroxylase can be ameliorated by restricting certain amino acids in the diet. -Phenylalanine is found in many types of food, including aspartame, and therefore by avoiding foods with high amounts of phenylalanine, the build-up pyruvate metabolites can be controlled. In contrast, skin pigments must be made from tyrosine and there is no way to do this if tyrosine metabolism is compromised.

Which of the following statements is a correct comparison of patients with type 1 versus patients with type 2 diabetes?

Patients with Type 1 diabetes are generally of normal weight whereas patients with type 2 diabetes are often obese

Uric acid is derived from both purine biosynthesis and by diet. What accounts for high levels of15N in excreted urine after feeding a patient 15N-glycine to diagnose the cause of gout? Explain.

The cause of the gout is excess production of uric acid because glycine is a precursor to purines.

Which of the structures above is a component of a glycerophospholipid?

The one with NH3+ only (not the one with two nitrogens)

Which of the following is consistent with the data presented in the feedback inhibition figure?

The product of the guanylate kinase reaction will inhibit the activity of PRPP synthetase.

Insulin-stimulated glucose uptake and utilization by skeletal muscle and liver cells results in a reduction in the blood glucose level. Which organ is primarily responsible for the decrease in serum glucose, and why?

The skeletal muscle is responsible for the majority of glucose uptake, as the total mass of skeletal muscle is greater than the mass of liver cells.

Cells cannot store excess amino acids such as aspartate and glutamate, which accumulate as aresult of protein degradation. Once the nitrogen is removed from aspartate and glutamate, what happens to thealpha-keto acids oxaloacetate and alpha-ketoglutarate, respectively?

These two alpha-keto acids are metabolized in the citrate cycle.

Which of the following is a common breakdown product between AMP and GMP degradation to uric acid?

Xanthine

Do PPARα-specific agonists theoretically offer more advantages for lowering cholesterol as compared to traditional statin drugs?

Yes, treatment with PPARα-specific agonists affects cholesterol transport and uptake as well as synthesis, whereas statins affect synthesis only.

a) The effect of cholesterol on membrane fluidity at physiological temperatures is to b) The effect of cholesterol on membrane fluidity at low temperatures is to

a) prevent lateral movement of phospholipids and thereby decrease membrane fluidity in that region b) maintain membrane fluidity through its disruption of fatty acid packing

When AMPK is bound by AMP and is phosphorylated at Thr172, _________ activity will _________.

acetyl-CoA carboxylase; decrease

What molecule signals the endothelial cell to produce nitric oxide, and what is the enzymatic reaction?

acetylcholine

Which of the following is secreted by visceral fat?

adipokines

Which of the following is directly affected by thiazolidinediones?

adipose tissue

What nitrogen source is used to produce carbonyl phosphate?

ammonia

Sort the phrases to correctly describe the role of anorexigenic and orexigenic neurons in regulating appetite and energy expenditure.

anorexigenic: signals for an increase in energy expenditure, activation initiated by leptin, signals adipocytes to store less fat

Which of the following combinations can be used by farmers to ensure robust nitrogen assimilation by actively growing crops?

applying cow manure to the fields as a source of fertilizer and always rotating in leguminous plants

What is the regulatory mechanism by which arginine stimulates flux through the urea cycle?

arginine stimulates the production of the allosteric activator N-acetylglutamate

In triacylglycerol synthesis, from where is the glycerol backbone derived?

dihydroxyacetone phosphate

Which symptom is the best indication of Phenylketonuria disease in a patient

elevated phenylpyruvate

Tobacco smoking, which is associated with a high risk of lung cancer, is described as:

environment

Glucose-6P is a central metabolite in human physiology and functions as a substrate or product in at least six metabolic pathways. What biochemical mechanisms determine glucose-6P flux through these pathways? Choose the THREE BEST answers below.

enzyme levels, allosteric control, and substrate availability

Tyr122 is important in the mechanism of the E. coli ribonucleotide reductase. The function of this amino acid in the mechanism is to ________________.

generate the Cys439 radical species

A deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD) is best described as:

genes --> environment

If the efficiency of the urea cycle decreased, there would be a buildup of which amino acid?

glutamine

Which of the following amino acids are required in the first step of heme biosynthesis?

glycine

What is the mechanism by which glyphosate, the active ingredient in Roundup, kills plants?

glyphosate is a competitive inhibitor of plant EPSP synthase

A tyrosine deficiency leads to muscle wasting and Kwashiorkor disease. What is the treatment?

high protein diet

Which of the following are ketone bodies?

hydroxybutyrate, acetoacetate

Which is found in the ketone body pathway?

hydroxybutyrate.

Aspartate is a(n) ________ amino acid, so if a person had a diet that contained no aspartate then ________.

nonessential; aspartate could be synthesized from other intermediates

The lack of an immune system in patients born with a defect in the enzyme adenosine deaminase of ADA-SCID is caused by _________ than normal activity of _________.

lower; ribonucleotide reductase

In order for a cancer cell to be resistant to the drug methotrexate, a mutation in the dihydrofolate reductase enzyme must be able to _____________.

maintain enzyme activity without being inhibited by methotrexate

Which symptom is the best indication of Lesch-Nyhan disease in a patient?

male infant with gout

Which of the following is NOT a cellular role for nucleotides?

membrane formation

Glycogen can provide fuel for both a short race (e.g., 200 m) and a long race (i.e., 10 K or more). Which of the following best describe(s) the use of muscle and liver glycogen during short and long races?

muscle glycogen can be used to fuel short AND long runs but liver glycogen can only be used to fuel long runs