Exam 3 Questions BIOC 385

both UTP and CTP.

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

Ribonucleotide reductase, E. coli, free radical, dinuclear, oxide ion

----- ----- contains two subunits, R1 and R2, that function as a tetrameric complex (R12R22). The catalytic mechanism in ---- is unusual in that it depends on formation of a(n) ----- to catalyze the reaction and requires contributions from a ----- iron center that is coordinated by an ---- ----.

-Enzyme levels. -Substrate availability. -Allosteric control.

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.

Deamination of cytosine generates uracil, which will result in a G-C to A-T mutation in DNA if uracil is allowed to persist. Evolution solved this problem by selecting for enzymes that constantly remove uracil from DNA

The pyrimidine thymine is only found in DNA, whereas the pyrimidine uracil is only found in RNA. What is the BEST explanation for this observation?

Deamination of cytosine generates uracil, which will result in a G-C to A-T mutation in DNA if uracil is allowed to persist. Evolution solved this problem by selecting for enzymes that constantly remove uracil from DNA.

The pyrimidine thymine is only found in DNA, whereas the pyrimidine uracil is only found in RNA. What is the one BEST explanation for this observation?

condensation of phosphoenolpyruvate and erythrose-4-phosphate.

The shikimate pathway involves the ________________

certain genes may have been advantageous in a culture when times off amine were routine but have become detrimental in modern society where food is in abundance

The thrifty gene hypothesis states that_____

AMP binding to AMPK facilitates formation of a salt bridge between R299-gamma and E364-alpha, which stimulates AMPK catalytic activity in the alpha subunit; ATP binding to AMPK does not form this salt bridge.

Which statement below describes the structural basis for allosteric control by AMP and ATP of AMP-activated protein kinase (AMPK) catalytic activity ?

increased fatty acid oxidation, increased oxidative phosphorylation, increased glycolytic flux

Which three processes show altered rates of metabolic flux in response to AMPK activation?

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

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

Accumulation of adenosine leads to excess dATP, which inhibits ribonucleotide reductase activity

Why does a defect in the enzyme adenosine deaminase cause the human disease ADA-SCID?

Both leptin and insulin lead to stimulation of anorexigenic neurons, such that appetite decreases and basal metabolic rate increases.

Why does it make sense that leptin and insulin both lead to stimulation of anorexigenic neurons?

Tadpoles living in water can excrete ammonia directly, but once on land, they need to excrete urea.

Why does it make sense that tadpoles (which live in water) have low levels of the enzyme arginase, but after metamorphosis into frogs (which live on land), their arginase levels increase?

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

Why does it makes sense that ghrelin stimulates orexigenic neurons?

Skeletal muscle and brain cells do not contain glucagon receptors.

Why don't brain and muscle respond to glucagon that is released from the pancreas in response to low blood glucose levels?

HGPRT deficiency prevents hypoxanthine salvage, leading to increased purine de novo synthesis

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

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

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

Carbohydrate will cause an increase in insulin and inhibit fatty acidoxidation later in the race, which will decrease available metabolic energy

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

Adipose

glucagon signaling stimulates fatty acid export by activating triacylglycerols hydrolysis at the surface of the lipid droplets in what type of tissue

Brain

insulin signaling stimulates neuronal signaling in the hypothalamus that leads to decreased eating and increased energy expenditure in what type of tissue

decrease the level of ketone bodies in the blood

partial inhibition of lipoprotein lipase would ---

porphyria

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

Ornithine is produced from arginine, allowing nitrogen excretion in the form of argininosuccinate

People with argininosuccinase deficiency have decreased ability to convert argininosuccinate into arginine in the urea cycle. Why is supplementing with L-arginine the best treatment for this disorder?

ATP; dATP

The overall activity of ribonucleotide reductase is regulated by allosteric binding of the activator and the inhibitor to the activity site

acetylcholine; L-arginine + 1.5 NADPH + H+ + 2O2 -> citrulline + NO + 1.5 NADP+

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

ammonia

What nitrogen source is used to produce carbamoyl phosphate?

Adenine (DNA and RNA)

What nucleoside is shown

Cytosine (DNA and RNA)

What nucleoside is shown

Guanine (DNA and RNA)

What nucleoside is shown

Thymine (DNA only)

What nucleoside is shown

Uracil (RNA only)

What nucleoside is shown

Oxidative phosphorylation and glycolysis

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

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

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

acetyl-CoA carboxylase; decrease

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

orexigenic

When the --- second-order neurons are activated, appetite increases and basal metabolic rates are decreased

insulin spike.

A steep drop in blood glucose concentration occurs after consumption of high glycemic index foods because of a(n)

8 6 7 3 1 4 2 5

-Urea excretion removes nitrogen derived from glutamate, glutamine, and aspartate. -Argininosuccinase generates fumarate and arginine from argininosuccinate. -Urea is formed following the hydrolytic cleavage of arginine by arginase. -Carbamoyl phosphate is combined with ornithine to form citrulline. -Glutamate dehydrogenase and glutaminase generate NH4+ -Citrulline is exported from the mitochondrial matrix to the cytosol. -Carbamoyl phosphate synthetase 1 generates carbamoyl phosphate. -Citrulline + aspartate combine to form argininosuccinate using ATP.

methotrexate; aminopterin

A compound is added to a cell and dihydrofolate reductase activity is reduced. If this compound is __________, it can be predicted that a similar result would be seen if __________ were added instead.

PRPP synthetase

A mutation in ____________ would decrease the synthesis of both AMP and GMP.

starvation

A negative nitrogen balance in a person would be an indicator of--

oxidation of homogentisate

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

phenylalanine

A person who has phenylketonuria will have an excess amount of ___________ in the cell.

1, 25-hydroxyvitamin D3 deficiency

A volunteer with Flying Samaritans brings a small boy to the local physician for treatment. Based on the background information listed below, what is the most likely biochemical basis for the boy's symptoms? =========== • The boy's body is hunched over and he is barely able to walk on his own • The physician noticed his wrists and ankles were thickened and enlarged • The patient's abdomen is distended and his breastbone is protruding • The volunteer measures his height and it is at the 30th percentile for age • The villagers live in a large cave during the day to avoid the hot sun

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

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

Glycogen synthase and acetyl-CoA carboxylase

AMP-dependent protein kinase (AMPK) is activated by low energy charge in the cell, which is the result of direct AMP binding to the gamma subunit and phosphorylation of Thr172. Name TWO enzymes that are inhibited by AMPK activation and thereby lead to increased ATP synthesis and a higher energy charge?

gastric juices; pepsinogen

After food enters the stomach, gastrin triggers the release of __________ and secretion of __________

Glucogenic

Alanine, cysteine, glycine, and serine are all considered __________ amino acids.

the enzyme tyrosinase working inefficiently

Albinism is caused by ---

20, 7, glycolysis, pentose phosphate, citrate cycle

All _____ amino acids are derived from just ______ metabolic intermediates, which are found in three metabolic pathways; _________, _________, and _______.

5-fluorouracil

An oncologist has a patient with dihydropyrimidine dehydrogenase deficiency. Which of the following is a chemotherapy agent that the doctor should be cautious about using with this patient because of serious side effects?

as a rapid source of NO for blood vessel dilation

Angina patients sometimes carry nitroglycerine pills with them___________

Tyrosine can be synthesized from phenylalanine, and since phenylalanine is essential, tyrosine is not.

Animals cannot synthesize tyrosine from shikimate-3P because they lack EPSP synthase. However, tyrosine is listed as a non-essential amino acid in most tables. What is the explanation?

only available from dietary sources.

Arginine, leucine, and lysine are all essential amino acids. This means that they are____________

nonessential; aspartate could be synthesized from other intermediates

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

-Leptin levels decrease when fat deposits decrease, which in turn, decreases the signal to eat less; metabolize more. The net result is that you eat more; metabolize less because your body thinks you are starving. -Food can be addictive to some people, much like narcotics. Therefore, the reward they get from binge eating leads to food cravings during diet-induced "withdrawal." -Insulin levels decrease when blood sugar decrease, which is one of the objectives of dieting, therefore it decreases the signal to eat less; metabolize more. The net result is that you eat more; metabolize less because your body thinks you are starving for sugar.

Based on what is known about neuronal control of energy metabolism in humans, why is it so hard to lose weight by dieting? Choose the three correct answers.

regulatory; R; CTP; T

Binding of ATP to the ______ subunit shifts ATCase to the ______ state, whereas ______ binding to the regulatory subunit stabilizes the ______ state.

Pepsin cleaves polypeptides, whereas secretin neutralizes pH back to 7

Compare the function of pepsin with that of secretin.

higher starting blood glucose level

Compared with a normal patient, a person with type 1 diabetes would display __________ during a glucose tolerance test.

-Supplying humans with the enzyme urate oxidase theoretically could be effective in reducing uric acid levels. -An inhibitor of xanthine oxidase, such as allopurinol, will limit the conversion of hypoxanthine to uric acid, and could be effective in reducing uric acid levels.

Defects in nucleotide metabolism that lead to a buildup of uric acid cause the disease gout. Select the TWO true statements below regarding potential treatments for gout.

-Supplying humans with the enzyme urate oxidase theoretically could be effective in reducing uric acid levels. -An inhibitor of xanthine oxidase, such as allopurinol, will limit the conversion of hypoxanthine to uric acid, and could be effective in reducing uric acid levels.

Defects in nucleotide metabolism that lead to a buildup of uric acid cause the disease gout. Select the two true statements below regarding potential treatments for gout

is degraded by

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

porphyrias.

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

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

Explain how a deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD) could lead to severe 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.

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

ATP is required for the GMP synthetase reaction leading to GMP production, and GTP is required for the adenylosuccinate synthetase reaction leading to AMP production.

Explain how regulatory cross-talk mechanisms within purine biosynthetic pathways ensure that pools of ATP and GTP are balanced.

When thymidine kinase is lacking, BrdU does not become phosphorylated and hence cannot be incorporated into DNA

Explain why cells with defects in thymidine kinase grow in media containing high amounts of 5-bromodeoxyuridine [BrdU], whereas cells with normal thymidine kinase will die when exposed to BrdU?

It works faster after it rains because the plants rapidly use up phenylalanine, which becomes limiting in the presence of glyphosate

Explain why glyphosate works faster in the summer after rain than after two weeks without rain.

Because carrier females have one normal X chromosome and one X chromosome with the mutation; males have a 50% chance of receiving the mutated X chromosome.

Explain why recessive X-linked mutations, such as those found in the PRPP synthetase and HGPRT genes, will only be present 50% of the time in males born to mothers who are asymptomatic carriers of the mutation.

1: L, 2:C, 3:P, 4:V

Fill in the missing amino acids using the single letter code for each.

Diet 3; because protein degradation yields carbohydrates; together providing proteins, carbs, and lipids.

Fish food used in aquatic farming can minimally consist of just tworequired dietary nutrients. This is because fish excrete NH4+ directlyinto water and thereby avoid ammonia toxicity. Which diet shown here is sufficient and safe to be used in aquatic farming? Explain. Diet 1: carbohydrate + lipid Diet 2: protein + carbohydrates Diet 3: protein + lipid Diet 4: nucleic acid + lipid

thymine/adenine

Five nucleotide bases are found in nucleic acids. Choose a pyrimidine/purine pair from the list below.

thymidylate synthase

Fluorodeoxyuridine--monophosphate is an inhibitor of the enzyme____________.

Skeletal muscle and brain because there are no glucagon receptors

Glucagon signaling has not effect on what type(s) of tissue

Liver

Glucagon signaling stimulates glucose export by increasing metabolic flux through gluconeogenisis and glycogen degradation pathways in what tissue.

GLP-1 stimulates insulin release by pancreatic beta cells to lower blood glucose levels.

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?

bilirubin; Jaundice

Hemoglobin is degraded by liver enzymes everyday. What is one of the products of hemoglobin degradation and what condition does it cause when accumulated in the blood?

bases are built on the ribose sugar

How are purine nucleotides built

base is built itself and then added to the sugar at the end

How are pyrimidine nucleotides built

No treatment for albinism; gray hair can be treated with dye

How do you cure albinism; how do you cure gray hair?

An increase of fatty acid mobilization, gluconeogenesis, ketogenesis, and protein degradation

How does metabolic flux change during starvation

Increased fatty acid mobilization, gluconeogenisis, ketogenesis, and protein degradation

How does metabolic flux change during starvation

C

If HCO3 that is radioactively labeled with 13C is available, which carbon atom in the molecule below would ultimately be expected to be radioactive?

ribonucleotide reductase

If the genomes of 100 different species were analyzed, gene sequences for which enzyme required for deoxyribonucleotide biosynthesis would most likely to be found in all of them?

maintain enzyme activity without being inhibited by methotrexate

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

1; 2

In purines, __________ nitrogen atoms and __________ carbon atoms originate from glycine.

cleaves trypsinogen to form trypsin

In the duodenum, enteropeptidase

inhibited; dATP

In the human disease called severe combined immunodeficiency (ADA-SCID), ribonucleotide reductase activity is __________ because of an overabundance of __________.

the citrate cycle.

In the production of urea, the carbon atom comes from______________.

signal transduction, energy conversion, genetic information, coenzyme function

In what four biochemical processes can you find the nucleotide base adenine?

protein phosphatase 2A; acetyl-CoA carboxylase

Insulin signaling in liver cells activates the enzyme --- which in turn activates the enzyme ---

phosphofructokinase-1

Insulin signaling increases the catalytic activity of ___________ in liver cells.

Liver

Insulin signaling stimulates glucose uptake by increasing metabolic flux through glycolytic, glycogen synthesis, and triacylglycerols synthesis pathways in what type of tissue

Adipose

Insulin signaling stimulates glucose uptake by increasing the GLUT4, leading to increased fatty acid and glycerol synthesis; activates fatty acid uptake from lipoprotein particles and promotes triacylglycerol storage in what type of tissue

Skeletal muscle

Insulin signaling stimulates glucose uptake by increasing the level of GLUT4 protein on the cell surface and also by increasing flux through glycolytic and glycogen synthesis pathways in what type of tissue

The severity of the phenylalanine hydroxylase deficiency and the amount of tyrosine in the diet of the individual.

It has been observed that some individuals with PKU have lighter skin than other individuals with PKU. What contributing factors explain this difference in pigmentation?

enhances protein denaturing.

It is important that proteolytic enzymes in the lysosome are optimized to work at low pH because low pH_____________.

increased gluconeogenesis and increased fatty acid oxidation.

Ketogenesis stimulated during starvation because it leads to______________.

protein degradation in skeletal muscle

Long term starvation (>30 days) leads to _______________.

E1

Match the classes of proteins involved in ubiquitination Enzymes that attach ubiquitin to E2 enzymes

E2

Match the classes of proteins involved in ubiquitination Enzymes that attach ubiquitin to target protein

E3

Match the classes of proteins involved in ubiquitination Ubiquitin ligases

Alpha-glucosidase inhibitor that delays dietary carbohydrate absorption.

Match the drug used to treat type 2 diabetes with its mechanism of action miglitol

Activates POMC gene expression in first-order neurons.

Match the drug used to treat type 2 diabetes with its mechanism of action. Dulaglutide

Directly activates insulin signaling in liver, muscle, and adipose cells.

Match the drug used to treat type 2 diabetes with its mechanism of action. Glargine

Stimulates insulin secretion by blocking K+ channels in beta cells.

Match the drug used to treat type 2 diabetes with its mechanism of action. Glipizide

Stimulates the activity of AMP-activated protein kinase.

Match the drug used to treat type 2 diabetes with its mechanism of action. Metformin

Activates expression of adipocyte genes required for fatty acid uptake.

Match the drug used to treat type 2 diabetes with its mechanism of action. Pioglitazone

-drink glucose -hour -type 1 diabetic -time -blood -glucose -type 1 diabetic -type 2 diabetic -type 2 diabetic -mg -deciliter

Match the letter shown in the graph with the correct label I F K C L H B E D J A G

Reduced levels of product

Match the metabolic disease with the correct biochemical mechanism. Albinism

Increased levels of substrate

Match the metabolic disease with the correct biochemical mechanism. Alkaptonuria

Reduced levels of product

Match the metabolic disease with the correct biochemical mechanism. Parkinson's disease

Increased levels of substrate

Match the metabolic disease with the correct biochemical mechanism. Phenylketonuria

optimal metabolite concentrations.

Metabolic homeostasis relies on maintaining___________________.

nitrogen gas

Nitrogen in biological compounds ultimately comes from ___________.

through conversion to aspartate

Nitrogen obtained from dietary proteins is incorporated into the urea cycle_____________.

reduced energy expenditure.

Nucleotide salvage pathways are favored in cells over de novo nucleotide synthesis because of __________________.

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

Obese individuals with type 2 diabetes are often prescribed metformin, which activates AMPK signaling. Why would metformin be an effective treatment for these individuals?

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

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

2, 4, 5, 8, 10

Phenylketonuria (1) / Albinism (2) is characterized by white skin due to a defect in the enzyme tyrosinase, which leads to a block in the pathway needed to synthesize adrenaline (3) / melanin (4). Animals with this condition have an increased risk of skin cancer (5) / mental illness (6). The genetic disease albinism (7) / phenylketonuria (8) is caused by a defect in the enzyme phenylalanine hydroxylase, which leads to the accumulation of tyrosine (9) / phenylalanine (10) derivatives that are toxic metabolites

1, 3, 5, 8, 10

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 is characterized by white skin and hair due to a defect in the enzyme arginase (7) / tyrosinase (8) and is characterized by a substrate accumulation (9) / lack of product (10) mechanism.

5, 1, 7, 2, 4, 6, 3

Put the following steps in the correct order describing target protein polyubiquitination. Once youhave numbered the steps, record your answer from top to bottom (a à g) and choose A, B, C, D, or E -E2 ubiquitinates a target protein Lys within the E2-ubiquitin-E3-target protein complex. - Ubiquitin is covalently attached to a cysteine in the E1 active site at position Gly76. -The polyubiquitinated target protein dissociates from the E2-E3 complex and is degraded. - E1 associates with E2 and transfers ubiquitin to a cysteine in the enzyme active site - A target protein binds to a specific E2-ubiquitin-E3 complex to initiate ubiquitination. -Three more ubiquitin moieties are attached through a Gly76-Lys48 peptide linkage. -E2-ubiquitin binds to an E3 enzyme to form a complex consisting of E2-ubiquitin-E3.

2, 5, 6, 4, 1, 3,

Put the following steps in the correct order for the ribonucleotide reductase reaction mechanism. Step 1 of the six step reaction mechanism is shown above to help you get started. -A thiyl free radical removes a hydrogen atom from the C-3' position of the ribose ring to generate a radical -Cation on C-2' is reduced by C462 creating the deoxynucleotide and the radical at C-3' is reduced by C439 -Deoxynucleoside diphosphate is released from the enzyme and C225-C462 disulfide bond is reduced by thioredoxin -A water molecule is removed in the reaction leaving behind a cation on C-2' that is stabilized by the radical on C-3' -A free radical at Y122 abstracts a hydrogen atom from C439 to form a cysteine thiyl radical -The hydroxyl group on C-2' of the ribose ring gains a proton from the C225 residue of the enzyme

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

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

target proteins and E3 ligases

Regulation of protein ubiquitination is most often mediated by modification of_____________.

1) Inhibits the shikimate pathway blocking synthesis of aromatic amino acids; 2) Glyphosate resistance innative plants (weeds) and human health problems including cancer..

Round-Up© is an herbicide called glyphosate made by the company Bayer, which acquired Monsanto in 2018. 1)How does glyphosate, work, and 2) What are two problems that have arisen due to overuse?

HGPRT; Lesch-Nyhan syndrome

The conversion of hypoxanthine to IMP is catalyzed by __________, which is deficient in __________.

phosphopentomutase; PRPP synthetase; phosphoriboxyl 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; phosphoribosyl transferase

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

lower; ribonucleotide reductase

The disease ADA-SCID is due to __________ than normal activity of the enzyme __________.

Nucleotidase

The enzyme _______ dephosphorylates nucleotides removing the phosphoryl group from the ribose sugar, forming nucleosides

X = ketone bodies; Y = glucose; Z = fatty acids

The graph below shows the relative changes in concentration of glucose, fatty acids, and ketone bodies during 40 days of starvation. Choose the answer that correctly labels the data on the graph.

lower; ribonucleotide reductase

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

cAMP

The molecule below is a precursor to the formation of which of the following second messengers?

a) metabolic pathways to synthesize essential amino acids require many enzymes b) arginase does not generate enough arginine in the urea cycle to support protein synthesis c) tyrosine is generated from phenylalanine, which is an essential amino acid in animals

The twenty amino acids needed for protein synthesis can be categorized in animals as essential or nonessential with regard to dietary sources. a) What is a characteristic of the biosynthetic pathways needed to generate essential amino acids? b) Why is arginine an essential amino acid even though it is generated by arginase in the urea cycle? c) Why is tyrosine a nonessential amino acid in animals even though they do not contain shikimate pathway enzymes?

beneficial; detrimental

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

3, 5, 7, 6, 1, 8, 4, 2,

Treatment of type 2 diabetics with GLP-1 agonists have been associated with weight loss and decreased A1C values, which reflect the percent of glycosylated hemoglobin in blood. A1C values are directly correlated to serum glucose levels over a 3-month period. Put the following steps in the correct order to explain how dulaglutide (Trulicity) injections result in weight loss and decreased A1C values by suppressing appetite and increasing energy expenditure. -POMC protein is processed to generate alpha-MSH hormone. -Activation of MC4 receptors on anorexigenic neurons. -Patient loses weight and has decreased blood glucose levels. -Neuronal signaling by anorexigenic neurons suppresses appetite and increases energy expenditure. -Trulicity binds to the GLP-1 receptor on POMC neurons. -Reduced percentage of glycosylated hemoglobin is reflected in a lower A1C value. -Alpha-MSH is secreted from POMC neurons. -GLP-1 receptor signaling activates POMC gene expression.

A) Inject insulin B) Type 2 diabetes C) Serum glucose D) Time (hours) E) Type 1 diabetes F) Normal

Type 1 and Type 2 diabetes are diagnosed with a clinical test following a 12 hour fast. Identify each of the parameters in the graph below by choosing the correct labels for letters A-F.

generate the Cys439 radical species

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

-Defects in the enzyme tyrosinase occur in every cell of the body and there is no way to replace this enzyme with 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. -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.

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 easily diagnosed at birth, but there is no treatment, which leads to an increased risk of skin cancer in these patients. Choose three statements that explain the reasons for these differences.

aspartate and carbamoyl phosphate

What are the sources for the two nitrogens in urea?

CAD, UMP synthase, CTP synthetase

What are the three target enzymes involved in the allosteric regulation of pyrimidine biosynthesis?

1) Overexpression of drug transporter, 2) DHFR mutation blocking drug binding, 3) DHFR gene amplification

What are three mechanisms by which cancer cells become resistant to the drug methotrexate?

Deficiency in the HGPRT enzyme; super active PRPP synthetase.

What are two of the three biochemical causes of gout?

High levels of tyrosine phosphorylated IRS-1 in insulin-sensitive muscle cells

What biochemical marker differentiates insulin-sensitive and insulin-resistant muscle cells?

Inject insulin and measure blood glucose levels over time

What clinical test distinguishes between Type 1 and Type 2 diabetes?

the base is built and then adds the ribose

What differentiates pyrimidine biosynthesis from purine biosynthesis?

Mutations outside of the enzyme active site can cause protein misfolding that lead to protein degradation.

What explains why a mutation the HGPRT gene that does not affect the catalytic activity of the enzyme can result in a loss-of-function mutation in patients with Lesch-Nyhan syndrome?

The positive charge on Arg blocks MTX binding to the active site.

What explains why the DHFR mutant L22R has a decreased affinity for the drug methotrexate (MTX)?

Base plus the sugar

What is a nuceloside

ribose + base + phosphate

What is a nucleotide

Allopurinol inhibits xanthine oxidase, which decreases the production of uric acid.

What is the biochemical basis for allopurinol treatment of gout?

Phenylbutyrate treatment leads to the production of phenylacetylglutamine, which is a soluble metabolite that reduces ammonia levels by removing glutamine.

What is the biochemical basis for giving individuals with hyperammonemia phenylbutyrate?

PKU is caused by a defect in the enzyme phenylalanine hydroxylase, which leads to accumulation of toxic phenylalanine metabolites; PKU treatment is to limit phenylalanine in the diet.

What is the biochemical basis for phenylketonuria and what is the treatment?

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

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

E3 functions as a target protein binding site to facilitate ubiquitination by E2

What is the biochemical role of the E3 enzyme in the proteasomal degradation of proteins?

Inhibition of NPY and AGRP gene expression through activation of JAK2/PI3K signaling

What is the effect of leptin receptor activation in NPY/AGRP first order neurons?

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 mutant mice, but leptin injections has no effect in the majority of people?

HGPRT adds hypoxanthine to PRPP to form IMP, which is converted to GMP and AMP to replenish nucleotide pools.

What is the function of the enzyme hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) in the nucleotide salvage pathways?

Glyphosphate is a competitive inhibitor of plant EPSP synthase

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

NH4⁺ + HCO3− + Aspartate + 3 ATP ⟶ Urea + Fumarate + 2 ADP + 2 Pi + AMP + PPi

What is the net reaction for the urea cycle

Arginine stimulates the production of allosteric activator N-acetyleglutamate

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

E) AMP-bound AMPK activity is higher in the presence of Thr172 phosphorylation.

What is the relative activity of AMP-bound AMPK in the absence and presence of Thr172 phosphorylation?

acetylcholine

What molecule signals the endothelial cell to produce NO?

1, 4, 2, 5, 3

Which FIVE of the following gene variants are good candidates to function as Thrifty Genes? 1) Acetyl-CoA carboxylase with high affinity for citrate 2) Glucokinase with decreased affinity for glucose 3) Decreased catalytic activity of fatty acyl-CoA synthetase 4) Hexokinase with decreased affinity for fructose 5) Acetyl-CoA carboxylase with low affinity for palmitoyl-CoA 6) Gherlin mutant with a low affinity for the ghrelin receptor 7) Decreased catalytic activity of fatty acid synthase 8) High basal level expression of Uncoupling Protein 1 9) Low activity lipoprotein lipase on the membrane of adipocytes

9, 6, 3

Which THREE of the following gene variants are good candidates to function as Thrifty Genes? (1) Acetyl-CoA carboxylase withhigh affinity for palmitoyl-CoA (2) High basal level expression ofUncoupling Protein 1. (3) Increased catalytic activity offatty acid synthase. (4) Increased catalytic activity offatty acyl-CoA synthetase (5) Acetyl-CoA carboxylase withlow affinity for citrate (6) Gherlin mutant with a highaffinity for the ghrelin receptor (7) Insulin receptor withdecreased affinity for insulin. (8) Glucokinase with decreasedaffinity for glucose. (9) High activity lipoprotein lipaseon the membrane of adipocytes

enteropeptidase

Which digestive protease is responsible for initiating the proteolytic cascade in the small intestine?

dihydrofolate reductase

Which enzyme activity would be directly inhibited by the addition of methotrexate?

Glucose-6-phosphate

Which metabolite listed below is considered central to human physiology based on its link to multiple biochemical pathways?

fumarate

Which metabolite listed below serves as the biochemical link between the urea cycle and the citrate cycle?

argininosuccinate

Which metabolite unique to the urea cycle connects the urea cycle to the citrate cycle through the "Krebs bicycle" pathway?

-increased thirst -blurred vision -obesity -slow-healing sores -frequent urination

Which of the five symptoms listed below are associated with undiagnosed Type 2 diabetes?

-Anorexigenic neurons send out signals that increase energy expenditure. -Ghrelin stimulates orexigenic signaling by binding to NPY/POMC neurons. -Orexigenic neurons increase fat stores.

Which of the following THREE statements are true regarding neuropeptides and appetite control?

Glycine

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

It is energetically expensive for the cell to solely rely on de novo biosynthetic pathways

Which of the following best explains why nucleotide salvage pathways evolved?

adipokines

Which of the following biomolecules is secreted by visceral fat?

FAD

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

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

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

L-arginine + 1.5 NADPH + H+ + 2O2 -> citrulline + NO + 1.5 NADP+

Which of the following is the reaction for nitric oxide synthase

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

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

E3

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