Lippincott's Biochemistry Chapter 20 - Amino Acids (Degradation and Synthesis) PDF

Amino Acids: Degradation and Synthesis I. OVERVIEW Amino acid degradation involves removal of the a-amino group, followed by the cata.bolism of the resulting cx-keto acids (carbon skeletons).These path- ways converge to form seven intermediate products: oxaloacetate, pyru- vate, a-ketoglutarate, f...

Amino Acids: Degradation and Synthesis I. OVERVIEW Amino acid degradation involves removal of the a-amino group, followed by the cata.bolism of the resulting cx-keto acids (carbon skeletons).These path- ways converge to form seven intermediate products: oxaloacetate, pyru- vate, a-ketoglutarate, fumarate, succinyl coenzyrne A (CoA), acetyl CoA, and acetoacetate. The products direcUy enter the pathways of intermedi- ary metabolism, resulting either in the synthesis of glucose, ketone bodies, or lipids or in the production of energy through their oxidation to carbon dioxide (CO:l) by the tricarboxylic acid {TCA) cycle. Figure.20.1 provides an overview of these pathways, with a more detailed summary presented in Figure 20.15 (seep. 269). Nonessential amino acids (Fig. 20.2) can be synthesized in sufficient amounts from the intermediates of metabolism or, as in the case of cysteine and tyrosine, from essential amino acids. In contrast, because the essential amino acids cannot be synthesized (or synthesized in sufficient amounts) by humans, they must be obtained from the diet in order tor normal protein synthesis to occur. Genetic detects in the pathways of amino acid metabolism can cause serious disease. II. GLUCOGENIC AND KETOGENIC AMINO ACIDS Amino acids can be classified as glucogenic, ketogenic, or both, based hQly s. Thr Tip Aan "" Al~ PTllUYAft CO:z-i f ACmnL c.A...l- _{j._ ;= L" ri~ 1L acnGACSTAft Lau I.ya Pile on which of the seven intermediates are produced during their catabo- OXAI DACaTATI Clll'l.18 lism (see Fig. 20.2). II ~ Melale 160d1rate Gin A. Glucogenlc amino acids 1f FUllAMft 1..an:KILUTARAft= f-001 It Glu -1S HIS \\ ;..co1 Amino acids whose catabolism yields pyruvate or one of the inter- /~ Pile Succlnate ~ SUCClllYLCDA4 Met 1e mediates of the TCA cycle are termed glucogenic. Because these Tyr Thr Val intermediates are substrates for gluconeogenesis (see p. 118), they can give rise to the net synthesis of glucose in the liver and kidney. BUii! CAN IDT = namae of 88V8n proclucta at amino acid Flgure20.1 Color-coding 11'181aboll m Amino acid metabolism shown as Red tut = nam of glucog1111lc amino acid a part of the essential pathways of ueed in ttlie Brown text nam of glucogwllc end ketogenlc mnlno aclde chapter: energy metabolism. (See Fig. 8.2, Grw taxt "' names of IC8log8l1lc amino acids Cyan taxt = one-carbon compounds p. 92, for a more detailed map of metabolism.) CoA = coenzyme A; CO-! "' carbon dioxide. 261 262 20. Amino Acids: Degradation and Synthesis B. Ketogenlc amino acids Gl'::cr°lc Glucogenic Kelogenic Amino acids whose catabolism yields either acetoacetate or one of Ketogenlc its precursors (acetyl CoA or acetoacetyl CoA) are termed ketogenic Alanine TyRlll {see Fig. 20.2). Acetoacetate is one of 1he ketone bodies, which also.Arginine include 3-hydroxybutyrate and acetone (see p. 195). Leucine and ,.-. Aaparaglne 'ii Aaparlal8 lysine are 1he only exclusively ketogenic amino acids found in pro- i! Cyatalne teins. Their carbon skeletons are not substrates for gluconeogenesis Glulmnata and, therefore, cannot give rise to 1he net synthesis of glucose. I z0 Glutamlne Glycine Prollne Ill. AMINO ACID CARBON SKELETON CATABOLISM '- SerlM The pathways by which amino acids are catabolized are conveniently ~ = organized according to which one (or more) of the seven intermediates HlstldlM lllOleuclna l.euc:IM llethlonlne Lyalne listed above is produced from a particular amino acid. Tl'INOnlne Valine Tryptophan A. Amino acids that form oxaloacetate Asparagine is hydrolyzed by asparaginase, liberating ammonia and Flgure20.2 aspartate (Fig. 20.3). Aspartate loses its amino group by transamination Classification of amino acids. [Note: to form oxaloacetate (see Fig. 20.3). [Note: Some rapidly dividing leuke- Some amino acids can become mic cells are unable to synthesize sufficient asparagine to support 1heir condlttonally essential. For example, growth. This makes asparagine an essential amino acid for these cells, supplementation with glutamine and arginine has been shown to which, therefore, require asparagine from 1he blood. Aspara.ginase, improve outcomes in patients with which hydrolyzes asparagine to aspartate, can be administered system- trauma, postoperative infections, and ically to treat leukemia. Aspara.ginase IC>\Yers the level of asparagine in immunosuppression.] the plasma, thereby depriving cancer cells of a required nutrient.] B. Amino acids that form a-ketoglutarate via glutamate 90Nt\ 9H2 1. Glutamlne: This amino acid is hydrolyzed to glutamate and HCNH~j~ ammonia by the enzyme glutaminsse (see p. 256}. Glutamate is coo- I converted to a-ketoglutarate by transamination or through oxida- tive deamination by glutamate dehydrogenase (seep. 252). - r:: Aaparaglne 2. Prollne: This amino acid is oxidized to glutamate. Glutamate is transaminated or oxidatively deaminated to form a-ketoglutarate. coo- l 3. Arginine: This amino acid is hydrolyzed by arginass to produce ornt- CH2 thine (and urea). [Note: The reaction occurs primarily in the liver as part HCNH8+ I of the urea cycle (see p. 255).J Ornithine is subsequently converted coo- to a-ketoglutarate, with glutamate semialdehyde as an intermediate. Aepartam ~a-Katogllllarate 4. Histidine: This amino acid is oxidatively deaminated by histidase to urocanic acid, which subsequently forms N-formiminoglutamate PLP +~ Glutamate ([FIGlu], Fig. 20.4). FIGlu donates its formimino group to tetrahy- coo- l drofolate (THF), leaving glutamate, which is degraded as described CfH2 above. [Note: Individuals deficient in folic acid excrete increased c=o I amounts of FIGlu in the urine, particularly after inges1ion of a large coo- dose of histidine. The FIGlu excretion test has been used in diag- OXALOACETATE nosing a deficiency of folic acid. See p. 267 for a discussion of folic acid, THF, and one-carbon metabolism.] Flgure20.3 C. Amino acids that form pyruvate Metabolism of asparagine and aspartate. PLP "" pyridoxal 1. Alanine: This amino acid loses its amino group by transamination phosphate; NHs =ammonia. to form pyruvate (Fig. 20.5). [Note: Tryptophan catabolism produces alanine and, therefore, pyruvate (see Fig. 20.10 on p. 265}.J Ill. Amino Acid Carbon Skeleton Catabolism 263 Flgure20A Degradation of histidine. NHa =ammonia. CH3 HCNHs+ 2. Sertne: This amino acid can be converted to glycine asTHF becomes I CO- ~- H '( bloptarln / '. ,.0 DOPA ClflV NADH + H+ t 1' Cetechol· emlMa.+ GTP A deficiency In dlhydroptflrldlne tedut:lase or any of lh enzymes of B"4 synthesis !Md to hyperphenylalanlnemla and decreased synthesis of catecholamlnea and serotonin. Figure 20.17 Biosynthetic reactions involving amino acids and tetrahydrobiopterin. [Note: Aromatic amino acid hydroxyfases use BH4 and not PLP (pyridoxal phosphate).] NAD(H) "" nicotinamide adenine dinucleotide; GTP ""guanosine triphosphate; DOPA"" L-3,4·dihydroxyphenylalanine; ~ =oxygen. VI. Amino Acid Metabolism Disorders 271 tyrosine hydroxy/as&- and tryptophan hydroxylas&--eatalyzed reac- Normal tions) improves the clinical outcome in these variant forms of hyper- phenylalaninemia, although the response is unpredictable.) ,' Phenylpyruvata - -- "" Phenyllacllde Screening of newborns for a number of treatable disorders, ''' including inborn errors of amino acid metabolism, is done by tandem mass spectrometry of blood obtained from a heel Phenylalanlne / Tl ua pratelna prick. By law, all states must screen for >20 disorders, with some screening for >50. All states screen for PKU. i ? ~ Melanln Tyroelne : : : ~ ~ catecholamln 1. Addltlonal characteristics: As the name suggests, PKU is also ~ Fumarat characterized by elevated levels of a phenylketone in the urine. AMtoacetat a. Elevated phanylalanlna metabolltee: Phenylpyruva1e (a phe- Phenylketonurla nylketone), phenylacetate, and phenyllactate, which are not normally produced in significant amounts in the presence of functional Rtt.H, are elevated in PKU (Fig. 20.18). These metabo- lites give urine a characteristic musty (''mousy") odor. - b. Central nervous system effects: Severe intellectual dis- Phenylalanlne ability, developmental delay, microcephaly, and seizures are. Tlaaua protBln characteristic findings in untreated PKU. The affected individ- ,. Melanln ual typically shows symptoms of intellectual disability by age '( -·- 1 year and rarely achieves an intelligence quotient (IQ) >50 Tyroel '~ - - -. - '... CatachDlamlnH (Fig. 20.19). [Note: These clinical manifestations are now rarely seen as a result of newborn screening programs, which allow Fumande early diagnosis and treatment.] Acetmc9bd8 c. Hypoplgmentatlon: Patients with untreated PKU may show a deficiency o1 pigmentation (fair hair, light skin color, and Figure 20.18 blue eyes). The hydroxylation of tyrosine by copper-requiring Pathways of phenylalanine tyrosinase, which is the first step in the formation of the metabolism in normal individuals and in patients with phenylketonuria. pigment melanin, is decreased in PKU because tyrosine is decreased. 2. Newbom screening and diagnosis: Early diagnosis of PKU is important because the disease is treatable by dietary means. 120 Because of the lack of neonatal symptoms, laboratory testing for elevated blood levels of phenylalanine is mandatory for detection. 100 However, the infant with PKU frequently has normal blood levels of 80 phenylalanine at birth because the mother clears increased blood phenylalanine in her affected fetus through the placenta. Normal g80 levels of phenylalanine may persist until the newborn is exposed to 40 24-48 hours of protein feeding. Thus, screening tests are typically done after this time to avoid false negatives. For newborns with a 20 positive screening test, diagnosis is confirmed through quantitative o~----"""T""-------.---------r-----...., determination of phenylalanine levels. Birth 2 6 8 Age(yeara} 3. Prenatal diagnosis: Classic PKU is caused by any of 100 or more different mutations in the gene that encodes PAH. The fre- Figure 20.19 quency o1 any given mutation varies among populations, and the Typical intellectual ability in untreated disease is often doubly heterozygous (that is, the PAH gene has a patients of different ages with different mutation in each allele). Despite this complexity, prenatal phenylketonuria. IQ= intelligence diagnosis is possible (seep. 493}. quotient 272 20. Amino Acids: Degradation and Synthesis 4. Treatment: Because most natural protein contains phenylalanine, 110 an essential amino acid, it is impossible to satisfy the body's protein requirement without exceeding the phenylalanine limit when ingest- ing a normal diet. Therefore, in PKU, blood phenylalanine level is 100 maintained dose to the normal range by feeding synthetic amino acid preparations free of phenylalanine, supplemented with some natural 90 foods (such as fruits, vegetables, and certain cereals) selected for 52 their low phenylalanine content. The amount is adjusted according to 80 the tolerance of the individual as measured by blood phenylalanine levels. The eartier treatment is started, the more completely neuro- 70 logic damage can be prevented. lndMduals who are appropriately treated can have normal intelligence. [Note: Treatment must begin 0 1 2 3 during the first 7-10 days of life to prevent cognitive impairment.] Y ra after dl11C011tlnua:tlon of diet Because phenylalanine is an essential amino acid, overzealous treatment that results in blood phenylalanine levels below normal Figure 20.20 is avoided. In patients with PKU, tyrosine cannot be synthesized Changes in intelligence quotient (IQ) from phenylalanine, and, therefore, it becomes an essential amino scores after dlscontlnuadon of low- acid and must be supplied in the diet. Discontinuance of the phe- phenylalanine diet in patients with nylalanine-restricted diet in early childhood is associated with poor phenylkelonuria. performance on IQ tests. Adult PKU patients show deterioration of IQ scores after discontinuatiOn of the diet (Fig. 20.20). Therefore, lifelong restriction of dietary phenylalanine is recommended. [Note: Individuals with PKU are advised to avoid aspartame, an artificial sweetener that contains phenylalanine.] 5. Maternal phenylketonurfa: If women with PKU who are not on a low-phenylalanine diet become pregnant, the offspring can be affected with maternal PKU syndrome. High blood phenylalanine in 1he mother has a teratogenic effect, causing microcephaly and con- genital heart abnormalities in the fetus. Because these developmen- tal responses to high phenylalanine occur during the first months of pregnancy, dietary control of blood phenylalanine must begin prior to conception and be maintained throughout the pregnancy. B. Maple syrup urine disease Maple syrup urine disease (MSUD) is a rare (1 :185,000), autosomal- recessive disorder in which there is a partial or complete deficiency in BCKD, the mitochondrial enzyme complex that oxidatively decarbox- ylates leucine, isoleucine, and valine (see Fig. 20.11 ). These BCM and their corresponding a-keto acids accumulate in the blood, caus- ing a toxic effect that interferes with brain functions. The disease is characterized by feeding problems, vomiting, ketoacidosis, changes in muscle tone, neurologic problems that can result in coma (primar- ily because of the rise in leucine), and a characteristic maple syrup- like odor of the urine because of the rise in isoleucine. If untreated, the disease is fatal. If treatment is delayed, intellectual disability results. 1. Clasalflcatlon: MSUD includes a classic type and several vari- ant forms. The classic, neonatal-onset form is the most common type of MSUD. Leukocytes or cultured skin fibroblasts from these patients show little or no BCKD activity. Infants with classic MSUD show symptoms within the first several days of life. If not diagnosed and treated, classic MSUD is lethal in the first weeks of life. Patients VI. Amino Acid Metabolism Disorders 273 with intermediate forms have a higher level of enzyme activity (up to 30% of normal). The symptoms are milder and show an onset from infancy to adolescence. Patients with the rare thiamine- dependent variant of MSUD respond to large doses of this vitamin. 2. Screening and diagnosis: As with PKU, prenatal diagnosis and newborn screening are available, and most affected individuals are compound heterozygotes. 3. Treatment: MSUD is treated with a synthetic formula 1hat is free of BCAA, supplemented with limited amounts of leucine, isoleucine, and valine to allow for normal growth and development without producing toxic levels. [Note: Elevated leucine is 1he cause of the neurologic damage in MSUD, and its level is carefully monitored.] Early diagnosis and lifelong dietary trea1ment are essential if the child with MSUD is to develop nonnally. [Note: BCAA are an impor- tant energy source in times of metabolic need, and individuals with MSUD are at risk of decompensation during periods of increased protein catabolism.] C. Alblnlsm Albinism refers to a group of conditions in which a defect in tyro- sine metabolism results in a deficiency in the production of melanin. These defects result in 1he partial or full absence of pigment from the skin, hair, and eyes. Albinism appears in different forms, and it may be inherited by one of several modes: autosomal recessive (pri- mary mode), autosomal dominant, or X linked. Total absence of pig- ment from the hair, eyes, and skin (Fig. 20.21), tyrosinas9-negative Figure 20.21 oculocutaneous albinism (type 1 albinism), results from an absent Patient with oculocutaneous albinism, or defective copper-requiring tyrosinase. It is 1he most severe form showing white eyebrows and lashes of the condition. In addition to hypopigmentation, affected individuals and eyes that appear red in color. have vision defects and photophobia (sunlight hurts their eyes). They are at increased risk for skin cancer. D. Homocys11nurta ~H The homocystinurias are a group of disorders involving defects in the 9H2 metabolism of Hey. These autosomal-recessive diseases are charac- 9H2 HCNH8+ terized by high urinary levels of Hey, high plasma levels of Hey and methionine, and low plasma levels of cysteine. The most common cause Coo- Homocystelne of homocystinuria is a defect in the enzyme cystathionine p-synthase, which converts Hey to cysta1hionine (Fig. 20.22). Individuals homozy- gous for cystathionine p-synthase deficiency exhibit dislocation of the lens (ectopia lentis), skeletal anomalies (long limbs and fingers), intel- lectual disability, and an increased risk for developing thrombi (blood clots). Thrombosis is 1he major cause of early death in 1hese individu- als. Treatment includes restriction of methionine and supplementation with vitamin B12 and folate. Additionally, some patients are responsive to oral administration of pyridoxine (vitamin Bs), which is converted to pyridoxal phosphate, the coenzyme of cystathionins p-synthase. These patients usually have a milder and later onset of clinical symp- toms compared with Ba-nonresponsive patients. [Note: Deficiencies in Flgure 20.22 methylcobalamin (see Fig. 20.8) or ftf,N10-MTHF reductase([MTHFRJ; Enzyme deficiency In homocystfnurla. see Fig. 20.12) also result in elevated Hey.] PLP =pyridoxal phosphate. 274 20. Amino Acids: Degradation and Synthesis E. Alkaptonurta Urine from a patient fl with alkaptonuria Alkaptonuria is a rare organic aciduria involving a deficiency in homogentisic acid oxidase, resulting in the accumulation of homo- gentisic acid (HA), an intermediate in the degradative pathway of tyrosine (see Fig. 20.15 on p. 269). The condition has three char- acteristic symptoms: homogentisic aciduria (the urine contains ele- vated levels of HA, which is oxidized to a dark pigment on standing, as shown in Fig. 20.23A), early onset of arthritis in the large joints, and deposition of black pigment (ochronosis) in cartilage and col- lagenous tissue {see Fig. 20.23B}. Dark staining of diapers can indi- cate the disease in infants, but usually no symptoms are present until about age 40 years. Treatment includes dietary restriction of phenylalanine and tyrosine to reduce HA levels. Although alkapton- uria is not life threatening, the associated arthritis may be severely crippling. [Note: Deficiencies in fumary/acetoacstate hydrofase, the terminal enzyme of tyrosine metabolism, result in tyrosinemia type I (see Fig. 20.15) and a characteristic cabbage-like odor to urine.] The specimen on tile left. 0 which has been etandlng for 15 minutes. hawa aome darkening at ttle VII. CHAPTER SUMMARY surface. due to the oxidation of hornogerrtlelc add. Amino acida whose catabolism yields pyruvate or an intermediate of the tltcarboxyllc acid cycle are tenned glucogenlc (Fig. 20.24). They can give rise to the net fonnation of glucose in the Hver and kidneys. r;t Vertebrae from a patient The solely glucogenic amino acids are glutamine, glutamate, proline,.., with alkaptonurla arginine, histidine, alanlne, serine, glycine, cystelne, methionine, vallne, threonine, aspartate, and asparaglne. Amino acids whose catabollsm yields either acetoacelate or one of its precursors, acetyl coenzyme A (CoA) or acetoacetyl CoA, arv termed ketogenlc. Leucine and lysine are solely k:etogenic. Tyrosine, phenylalanine, tryptophan, and isoleucine are both ketogenic and glucogenic. Noneaentlal amino acids can be synthesized from metabolic intermediates or from the carbon skeletons of essential amino acids. Eaaentlal amino aclda need to be obtained from the diet. They include histidine, methionine, threonine, valine, isoleucine, phenylalanine, tryptophan, leucine, and lysine. Phenylketonurla (PKU) is caused by a deficiency of phenylalanine hydrox.yl11ae (PAH), which converts phenylalanine to tyrosine. Hyperphenylalanlnemla may also be caused by deficiencies In the enzymes that synthesize or regenerate the coenzyme for PAH, tetrahydroblopterln. Untreated lndlvlduals with PKU suffer from severe intellectual disability, developmental delay, microcephaly, seizures, and a characteristic musty (mousy) smell of the urine. Treatment involves controlling dietary phenylalanine. Tyrosine becomes an essential dietary component for people with PKU. Maple ayrup urine dlaeaee (MSUD) is caused by a partial or complete deficiency in btt1nched- chllin a-lceto acid dehydrogenue, the enzyme that decarboxylates the branched-chain amino acids (BCAA) leuclne, lsoleuclne, and vallne. SymptOms include feeding problems, vomiting, k:etoacidosis, changes in muscle tone, and a characteristic sweet smell of the urine. If untreated, Figure 20.23 the disease leads to neurologlc problems that result In death. Treatment Specimens from a patient with involves controlling BCAA intake. Other important genetic diseases alkaptonuria. A. Urine. B. Vertebrae. associated with amino acid metabolism include albinism, homocystlnurla, methylmalonlc acldemla, alkaptonurla, hlstldlnemla, tyroalnemla, and cystathlonlnurla. VII. Chapter Summary 275 Metabollsm of amino aclda I Some clinically important amino acids I [ Malhlonlne I I Phenylalanlne ) Soun:e of m.thyl graups Pracurmr of tyrosine ~[ In metabolism Elevetad In phanyllattonurta catabollsm of amino aclda J Precuraor of cystelne I involv8s I [ Arglnln I I Hlslldln ) Component of t t u--.cycl Pracurmr of hl8tamlne - - [ Removal o1. a-amino group ll Metabollam o1. carbon skeletons I Pnlcuraor o1 nlb1c oxide I Elevated In hllllldlnemla Tryptophan l conWl!gQS'to produce t [ Glutemlne I Pracurmr of aerotonln I Se¥9n productll ) Storage and tranaport I Alanlne ) I form or ammonia consf8tb1a of lhmaport form of Precursor of purtnee ammonia from muKle + t and p,rtmldlnes K8y glucogenlc unlno acid I ACl'TYLCoA P'YRUVA,. IACITOACSTYL CoA OXALOACETATE FUllARATE Cl-ICETOGLUTARATE c/usified as 8UCClllYL CoA ~- [ I Metabolic defects in amino metabolism chs.racterlzsd by l i t [ Ketogenie ~ t )[ Glucogenlc ~ ; ) t Famlly of d8fect8 In enzvmee of amino acid matabollam can be. [ Screened for In newborns I I UDlds UDlds I ca.ussdby [ Energy Energy l Glucose 1n11erttance la 1'9C8881v8; Point mutations, delellorui, UBUBlly heterozygotee uaually do not spllclng rors allow symptoms cM lead to I which trea~by -+-[ Synthesis of amino acids t Partlally or completely 1 I Involves Inactive enzyme [ Dlelary restrtctlon I which leads to - Tranaamlnallon of i>klllo acids, t for example, Accumulallon of aubetrata mn~ [ Characb!rlllllc amell or pyruvate ~ alanlna and a dellclency or tile d8fectlv8 enzyme's product the urine I - Amldatlon, for example, aapande ~ aaparaglna which leads f to Dlaturbancea In metabollam, parllcularly the central...._,, - Syntheel tram otll amino acids, for example. phenylalanlne ~ tyrosine nervoua system (CNS) I which le8ds to t j -- -- _. 19 -~.! [ Selzu...._ Intellectual dlaablllty, otll CNS arrecta l ,. ·· ~ T.~ ;I Conc pt connect >. -~- Figure 20.24 Key concept map for amino acid metabolism. CoA"' coenzyme A. 276 20. Amino Acids: Degradation and Synthesis Study Questions Correct answers "' F. A, D. A deficiency in cystathionine !'-synthase of methionine degradation results in a rise in Choose the ONE bast answer. homocysteine. A deficiency in homogentisic acid oxidase of tylQSine degradation results in a rise in homogentisic For Questions 20.1-20.3, match the deficient enzyme with acid, which forms a black pigment that is deposited in the associated clinical sign or laboratory finding in urine. connective tissue (ochronosis). A deficiency in tyroeinase results in decreased formation of melanin from tyrosine in A. Black pigmentation E. Increased branched- the skin, hair, and eyes. A sweaty feel-like odor is char- of cartilage chain amino acids acteristic of iaoveleryl ooenzyme A dehydrogenase defi- B. Sweaty feet-like F. Increased ciency. Cystine crystals in urine are seen with cystinuria, a odor of fluids homocysteine defect in intestinal and renal cysline absorption. Increased branched-chain amino acids are seen in maple syrup urine c. Cystine crystals in G. Increased methionine disease, increased methionine is seen in defects in homo- urine H. Increased cystsine metabolism, and increased phenylalanine is seen D. While hair, red eye phenylalanine in phenylkelonuria. color 20.1 Cystathlonlne JJ-synthase Correct answer = D. In patients with phenylketonuria, 20.2 Homogentisic acid oxidase tyrosine cannot be synthesized from phenylalanine and, hence, becomes essential and must be supplled In the diet. 20.3 Tyrosinase Phenylalanlne In the diet must be controlled but cannot be ellmlnated entirely because It Is an essentlal amino acid. 20.4 A 1-week-old infant, who was bom at home in a rural, Dietary treatment must begin during the first 7-10 days medically-underserved area, has undetected classic of llfe to prewnt Intellectual dlsablllty, and llfelong restrlo- don of phenylalanine Is recommended to prevent cognitive phenylketonuria. Which statement about this baby and.I decllne. Addlllonally, elevated levels of phenylalanine are or her treatment is correct? teratogenic to a developing fetus. A. A diet devoid of phenylalanine should be initiated immediately. B. Dietary treatment will be discontinued In adulthood. Correct answer = D. Methionine is Iha precursor of cys- C. Supplementation with vitamin Be is required. teine, which becomes essential if methionine is severely D. Tyrosine is an essential amino acid. restricted. Alanine is a key glucogenic amino acid. Acelyl coenzyme A (CoA) cannot be used for the net synthesis of 20.5 Which one of the following statements concerning glucose. Amino acids catabolized to acetyl CoA are keto- amino acids is correct? genic. Branched-chain amino acids are catabolized primar- ily in skeletal muscle. A. Alanine is keloganic. B. Amino acids that are catabolized to acetylcoenzyme A are glucogenlc. The three a:-keto acid dehyclrogenase complexes (pyruvate C. Branched-chain amino acids are catabolized dehyclrogenase (PDH], u-ketoglutarate dehydrogenase, and primarily in 1he liver. branched-chain o:-keto acid dehydrogenase [BCKD]) have D. Cysteine is essential for individuals consuming a dihydrolipoyl dehydrogenese (Enzyme 3, or E3) in com- diet severely limited in me1hionine. mon. In ES-deficient maple syrup urine disease, in addition to the branched-chain amino acids and their a:-keto acid 20.6 In an individual with the dihydrolipoyl dehydrogenase derivatives accumulating as a result of decreased activity of (E3)-deficient form of maple syrup urine disease, why BCKD, lactate will also be increased because of decreased would lactic acidosis be an expected finding? activity of PDH. 20.7 In contrast to the vitamin Ba-derived pyridoxal phosphate required in most enzymic reactions involving Tetrahydrobiopterin, made from guanosine triphosphate, is amino acids, what coenzyme is required by the aromatic the required coenzyme. amino acid hydmxylases?