Protein Biochemistry

Question 1

Urea Cycle comprises the following:

Answer 1

Ornithine is the backbone that is recycled in this process

1. Ornithine—> Citrulline
   i. catalyzed by Ornithine transcarbamylase
2. Citrulline + Aspartate—> Argininosuccinate
   i. (catalyzed by Arginonosuccinate synthase)
3. Argininosuccinate–> Arginine
   i. (catalyzed by Argininosuccinate lyase)
4. Arginine–> Ornithine + Urea
   i. (catalyzed by Arginase)

Question 2

Carbamoyl phosphate synthetase I (initial step in Urea Cycle entry)

Answer 2

a. Important urea cycle enzyme found in mitochondria.
i. Carbamoyl phosphate synthetase I: Ornithine—> Citrulline

b. Reaction: bicarbonate + ammonia–> carbamoyl phosphate uses 2 of the 3 ATPs in urea cycle.
c. N-acetylglutamate is an allosteric activator of Carbamoyl phosphate synthetase I.
d. Arginine is an activator of N-acetylglutamate synthase, which catalyzes the following reaction: acetyl CoA + glutamate to N-acetylglutamate

Question 3

Transport of ammonia

Answer 3

a. Ammonia cannot be transported through blood, so alternative mechanisms are needed such as those that rely on urea.
b. Glutamine serves as a means of transport, since it can “hold” two ammonia groups.
c. Glu dehydrogenase serves as a control pt for protein metabolism specifically by controlling the direction of either nitrogen removal or incorperation into amino acids
d. Most tissues use glutamine synthetase to convert glutamate to glutamine for transport to the liver (to enter the urea cycle).

Question 4

How muscle is unique in ammonia transport

Answer 4

a. Muscle is different where alanine is used instead of glutamine for transport in the Alanine-Glucose Cycle.
b. This is because in muscle there is a build-up of pyruvate from glycolysis and pyruvate can be converted to alanine for transport to liver (transamination).
c. The liver, in turn, can use the alanine to convert back to pyruvate (transamination) and glucose remade (gluconeogenesis) can then be delivered back to the muscle.

Question 5

Arginine in nerve and muscle function (X-talk and alternative reactions related to urea cycle).

Answer 5

a. NO synthase converts arginine–> citrulline to produce NO, an important molecule used as a neurotransmitter.
b. In the urea cycle, arginine–> ornithine can either be catalyzed by arginase or alternatively can be catalyzed by several enzymes to produce creatine phosphate for energy (muscle).

Question 6

Ketogenic versus glucogenic (categorizing the breakdown of amino acids) describes the outcome of the keto acid

Answer 6

a. Glucogenic: produces pyruvate or Kreb Cycle intermediates.
b. Ketogenic: produces no net production of glucose.

c. Examples:
i. Glucogenic: Oxaloacetate in Kreb Cycle comes from aspartate transamination
ii. Ketogenic: Lysine and leucine are the ketogenic amino acids since breadown gives Acetyl-CoA (i.e. only 2 carbons)

Question 7

Decarboxylation of branched-chain amino acids

Answer 7

a. Branched Chain Amino Acids include leucine, valine, and isoleucine.
b. First, these three amino acids are deaminated by branched-chain aminotransferase to produce a-keto acids.

c. Second, they are decarboxylated by branched-chain a-ketoacid dehydrogenase complex.
i. Maple Syrup Urine Disease (MSUD) occurs when this dehydrogenase complex is deficient and there is consequently a build up of the a-keto acids in urine (“sweet smelling”).

Question 8

Maple Syrup Urine Disease (MSUD)

Answer 8

a. Maple Syrup Urine Disease (MSUD) occurs when this branched-chain a-ketoacid dehydrogenase complex is deficient and there is consequently a build up of the a-keto acids in urine (“sweet smelling”).

b. Normally, these three amino acids are deaminated by branched-chain aminotransferase to produce a-keto acids.
i. Second, they are decarboxylated by branched-chain a-ketoacid dehydrogenase complex.

c. Without the Decarboxylation step, there will be a build up of alpha-keto acids

Question 9

Thyroid Chemistry
(product derived from Tyr)

Answer 9

a. Tyrosine is used to make T4 (prohormone) that is converted to T3 (hormone).
b. Thyroid stimulating hormone (TSH): Stimulates iodide (I-) uptake and stimulates release of T4,T3.

c. Thyroid peroxidase: Oxidizes iodide (I-) to (I2).
i. Thyroglobulin (Tg): Contains Tyr residues iodinated to form T4,T3.
ii. Thyroxin binding globulin (TBG): Transports T4,T3.

Question 10

Porphyrin (Heme) Summary

specialized products derived from Gly and TCA intermediate

Answer 10

a. Porphyrins such as Heme are cyclic molecules made of 4x pyroles primarily produced in liver.
i. Porphyrins bind Fe2+ (iron).

b. To produce a porphyrin the following reactions take place:
1. Gly + succinyl CoA—> δ -Aminolevulinic acid (ALA) (catalyzed by δ-Aminolevulinate synthase)

2. 2xALA—> Porphobilinogen (catalyzed by by δ-Aminolevulinate dehydratase)
3. Porphobilinogen—-> Protoporphyrin IV (catalyzed by 4 enzymes)
4. Protoporphyrin IX—> Heme (catalyzed by Ferrochelatase)
   c. Porphyrias are the general term for diseases in porphyrin synthesis.
   d. Lead inhibits two enzymes in porphyrin synthesis (δ-Aminolevulinate dehydratase, ferrochelatase)”lead poisining”.

Question 11

To produce a porphyrin the following reactions take place:

Answer 11

1. Gly + succinyl CoA—> δ -Aminolevulinic acid (ALA) (catalyzed by δ-Aminolevulinate synthase)
2. 2xALA—> Porphobilinogen (catalyzed by by δ-Aminolevulinate dehydratase)
3. Porphobilinogen—-> Protoporphyrin IV (catalyzed by 4 enzymes)
4. Protoporphyrin IX—> Heme (catalyzed by Ferrochelatase)

Question 12

Porphyrin (Heme) degradation:

Answer 12

a. Reactions Heme—> biliverdin (green)—> bilirubin (red-orange)—> bilirubin diglucuronide—> urobilinogen–> stercobilin (brown)
b. Bilirubin is transported in blood via albumin.
c. In liver, bilirubin is conjucated with glucuronic acidbilirubin diglucuronide (or otherwise known as conjugated bilirubin).
d. In intestine, bilirubin diglucuronide is oxidizedstercobilin.
e. Jaundice occurs when bilirubin cannot be processed properly (i.e. hemolytic jaundice occurs when too many RBCs lyse, neonatal jaundice when bilirubin diglucuronide is not produced fast enough by low levels of bilirubin glycuronyltransferase).

Question 13

alanine aminotransferase (ALT)

Review

Answer 13

ALT catalyzes the transfer of an amino group from L-alanine to α-ketoglutarate, the products of this reversible transamination reaction being pyruvate and L-glutamate.

L-glutamate + pyruvate ⇌ α-ketoglutarate + L-alanine

*NH3 moves from the Glutumate to the Alanine

Question 14

Aspartate aminotransferase
(AST)

Review

Answer 14

Aspartate transaminase catalyzes the interconversion of aspartate and α-ketoglutarate to oxaloacetate and glutamate.

Aspartate (Asp) + α-ketoglutarate ↔ oxaloacetate + glutamate (Glu)

*NH3 moves form Asp to the Glu

Question 15

Urea Cycle Introduction

Answer 15

a. The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions occurring in many animals that produces urea ((NH2)2CO) from ammonia (NH3).
i. In mammals, the urea cycle takes place primarily in the liver, and to a lesser extent in the kidney.

b. Organisms that cannot easily and quickly remove ammonia usually have to convert it to some other substance, like urea or uric acid, which are much less toxic.
i. Insufficiency of the urea cycle occurs in some genetic disorders (inborn errors of metabolism), and in liver failure. The result of liver failure is accumulation of nitrogenous waste, mainly ammonia, which leads to hepatic encephalopathy.

Question 16

Urea Cycle

*Critical Slide

Answer 16

a. The urea cycle consists of five reactions: two mitochondrial and three cytosolic.
b. The cycle converts two amino groups, one from NH4+ and one from Asp, and a carbon atom from HCO3−, to the relatively nontoxic excretion product urea at the cost of four “high-energy” phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP).
c. Ornithine is the carrier of these carbon and nitrogen atoms.

Question 17

The Urea Cycle

Overview

Answer 17

Net Reaction:

3ATP + HCO3- + NH4(N)+ + Aspartate(N) ——-> 2ADP + AMP + 2Pi + PPi + fumarate + urea

Question 18

What is the Control point for Protein Catabolism (Urea Cycle)

Answer 18

Carbamoyl phosphate synthetase I:

a. Important urea cycle enzyme found in mitochondria.

b. Reaction:
2ATP + HCO3− + NH4+ –> 2ADP + Carbamoyl phosphate + Pi

c. N-acetylglutamate is an allosteric activator of Carbamoyl phosphate synthetase I.
i. Arginine is an activator of N-acetylglutamate synthase, which catalyzes the following reaction: acetyl CoA + glutamate to N-acetylglutamate

Question 19

Carbamoyl phosphate synthetase I

is a control point for protein catabolism

Answer 19

a. The reaction catalyzed by Carbamoyl phosphate synthetase I is one of the most complicated known.

b. Uses two ATPs to add one phosphate and ammonia.
i. ~10 mutations found in this enzyme lead to early onset of associated
ii. “urea cycle disorder” (with subsequent increased ammonia in blood).

Question 20

Transport of ammonia

Answer 20

a. Because ammonia is toxic, glutamine is used to transfer it from peripheral tissues to the
• Kidneys where it is removed in the form of ammonia (through urine).
• Liver where it is removed in the form of urea (through blood to kidney).

Question 21

Muscle versus other tissues transport Nitrogen a different way to the tissues

*Critical Slide

Answer 21

a. Most tissues use glutamine synthetase to convert glutamate to glutamine for transport to the liver (to enter the urea cycle).

b. Muscle is different where alanine is used instead of glutamine for transport in the Alanine-Glucose Cycle.
i. This is because in muscle there is a build-up of pyruvate from glycolysis and pyruvate can be converted to alanine for transport to liver (transamination).
ii. The liver, in turn, can use the alanine to convert back to pyruvate (transamination) and glucose remade (gluconeogenesis) can then be delivered back to the muscle.

Question 22

Transport of ammonia

Different Tissues

Answer 22

a. Liver: Urea Cycle produces urea for transport through blood to kidney.
b. Peripheral Tissue: Glutamine produced for transport to Liver.
c. Muscle: Alanine produced for transport to Liver.
d. Kidney: Removes urea and remove ammonia (from Gln).

Question 23

Glutamate dehydrogenase is a control points for protein catabolism

Answer 23

a. Allosterically regulated and serves as another control pt for catabolism (i.e. goes both ways).
Reaction: Glutamate + NAD alpha Ketoglutarate + NH4+

b. Genetic mutation in ATP/GTP binding site results in hyperinsulinism-hyperammonemia
syndrome: elevated levels of ammonia in blood (“gain of function mutation”).

Question 24

Control points for protein catabolism

*Four that need to be known

Answer 24

a. The directionality of transamination (by ALT & AST) is regulated by the
relative concentrations of “substrates” and “products”.

b. N-acetylglutamate is a required activator of carbamoyl phosphate synthetase I that kick starts the Urea Cycle (i.e. protein degradation).
c. The directionality of oxidative deamination by Glu dehydrogenase depends on the relative concentrations of Glu,α-ketogluterate,NH3.
d. ATP & GTP are allosteric inhibitors of Glu dehydrogenase, while ADP & GDP are activators.

Question 25

Amino acid metabolism

i.e. connection to other cycles

Answer 25

a. NH3 from deaminated amino acids goes to the Urea Cycle.

b. Also yield α-keto acids that, directly or via additional reactions, feed into other major metabolic pathways
(e. g. Krebs Cycle).

c. Amino acids are grouped into classes, based on whether or not their carbon skeletons can be converted to glucose:
1) Glucogenic = Produce pyruvate or Kreb Cycle intermediates
2) Ketogenic = No net production of glucose
3) Both

Question 26

Ketogenic metabolism

Answer 26

Ketogenic (Leu, Lys) amino acid breakdowns do NOT give net production of glucose

TWO Carbons in & Two Carbons out

Question 27

Glucogenic breakdowns

Answer 27

a. The 4-C Krebs Cycle intermediate oxaloacetate is produced from aspartate.

b. Aspartate transamination yields oxaloacetate.
i. use oxaloacete for gluconeogenisis

*Aspartate is also converted to fumarate in Urea Cycle. Fumarate is converted to oxaloacetate in the Krebs cycle.

Question 28

Maple Syrup Urine Disease (MSUD)

Answer 28

a. Branched chain amino acids are Val, Ile, Leu.

b. They share common metabolic pathway:
1) Branched Chain Aminotransferase deaminates.
2) Branched Chain α-Keto Acid Dehydrogenase
(BCKDH) is a multi-subunit complex homologous
to Pyruvate Dehydrogenase complex.

c. Genetic deficiency of BCKDH is called Maple Syrup Urine Disease (MSUD).

d. MSUD leads to high concentrations of branched chain keto acids in urine give it a characteristic odor.
i. Could be lethal if not treated.

Question 29

Thyroid Chemistry

Answer 29

a, T4 is a “prohormone” that is converted to the hormone T3 (Deiodinase).

b. T4,T3 are transported from thyroid through blood via Thyroxin Binding Globulin (TBG).
How is T3 and T4 made?

Question 30

Thyroid Chemistry

Crummy bullet points

Answer 30

a. Thyroid stimulating hormone (TSH):
i. Stimulates iodide (I-) uptake.
ii. Stimulates release of T4,T3.

b. Thyroid peroxidase:
i. Oxidizes iodide (I-) to (I2).

c. Thyroglobulin (Tg):
i. Contains Tyr residues iodinated to form T4,T3.

d. Thyroxin binding globulin (TBG):
i. Transports T4,T3.

Question 31

Porphyrin (Heme) Synthesis

Answer 31

a. Heme is a “porphyrin” produced in liver.
b. Porphyrins are cyclic molecules that bind metals (Fe2+).
c. Porphyrias are inherited defects in heme synthesis.

Question 32

Regulation of Heme Synthesis

Answer 32

a. Initial reactions ALAS1, ALAS2 are inhibited by end-product.
b. δ-Aminolevulinic acid (ALA) dehydratase is Zn-dependent.

c. Lead—> anemia, “lead poisoning”.
•can replace Zn in ALA dehydratase.
•can replace Fe2+ in ferrochelatase.

Question 33

Heme Degradation

Answer 33

a. Heme is degraded to bilirubin
b. High bilirubin leads to jaundice (yellow color).
c. Bilirubin is also an anti-oxidant.
d. Bilirubin glucuronyl-transferase is low in infants (especially premature).

e. Fluorescent light converts bilirubin to more polar products, allowing
removal similar to conjugated bilirubin.

Question 34

Met and Cys comprise the two sulfer-containing amino acids

Answer 34

a. Cysteine (an unessential amino acid) is unique in that the –SH can form disulfides with another Cys, which is important for the structural integrity of many proteins (especially extracellular proteins).
i. Glutathione (GSH): tripeptide that controls redox potential via GSHGSSG, where cysteine is the central amino acid that actually does the work here.

b. Methionine (an essential amino acid) is unique in that it is used to produce S-adenosylmethionine, which is also an intermediate in the production of cysteine.
i. S-adenosylmethionine (SAM): produced in the first step of methionine degradation and converted to S-adenoyslhomocysteine (SAH).
ii. SAM is major Carbon donor and a “high energy storage unit” like ATP.

Question 35

Met, Cys Degradation

sulfur containing amino acids

Answer 35

Recycling Met reactions:
Met–> SAM–> SAH—> Homocysteine—> Met
i. HomocysteineMet needs THF and Vit-B12 to transfer back CH3 group.

Question 36

Met, Cys Diseases:

Answer 36

a. Hyperhomocysteinemia: elevated levels of homocysteine cause multiple problems that include cardiovascular disease.
i. Results from low levels of folate, B6, & B12 (vascular disease).
ii. Cysteine is now essential and treat with folate, B6, & B12.

b. Homocystinuria: results from defect in cystathionine-b-synthase (CBS) and cannot convert homocysteine to cystathionine (and eventually cysteine).
i. Leads to mental retardation, osteoporosis, & vascular disease. Cysteine is now essential. Can treat with Vit B6 to “force” CBS activity.

c. Cysteinuria : kidney stones (renal failure), due to defective in transporter of cysteine (& Ornithine, Lysine, Arginine) that leads to crystallization in urea, treat with acetazolamide that makes cysteine more soluble

Question 37

Several cofactors are used for transferring carbons

Answer 37

a. SAM as discussed above.
i. S-adenosylmethionine (SAM): produced in the first step of methionine degradation and converted to S-adenoyslhomocysteine (SAH).
ii. SAM is major Carbon donor and a “high energy storage unit” like ATP.

b. Tetrahydrofolate (THF) is synthesized in bacteria and its precursor, folate, is a vitamin for mammals.
i. The one-carbon group, in any of three oxidation states, is bonded to N-5 or N-10 or to both.
ii. The most reduced form of the cofactor carries a methyl group, a more oxidized form carries a methylene group, and the most oxidized forms carry a methenyl, formyl, or formimino group.
iii. The different forms of tetrahydrofolate are interconvertible and serve as donors of one-carbon units in a variety of biosynthetic reactions.

Question 38

Glutathione (GSH) as a redox buffer

Answer 38

a. GSH is a highly soluble tripeptide as opposed to Cys.
b. As high as millimolar in some tissues.

c. Functions:
i) thiol acts as redox buffer (“SH buffer”) to maintain proteins in their reduced forms (i.e. intracellular proteins) and regulate activity (i.e. enzymes)
ii) Cofactor for several enzymes (i.e. Glutathione transferase, GST).
iii) Reduce hydrogen peroxide (H2O2) to water and general protection against ROS (radical oxidizing species).

Question 39

Tryptophan Metabolism

Answer 39

a. Trp is metabolized to pyruvate or acetyl-CoA.
b. Trp is first hyroxylated by tryptophan hydroxylase using tetrahydrobiopterin (BH4) as a cofactor
c. Trp is used to produce serotonin (neurotransmitter), melatonin (hormone), and niacin (energy).

Question 40

Phe & Tyr Metabolism

Answer 40

a. Phe, Tyr are metabolized to fumerate or acetoacetate.
b. Phe is hydroxylated by phenylalanine hydroxylase to produce Tyr using BH4 cofactor

c. Tyr is hydroxylated by tyrosine hydroxylase to produce DOPA using BH4, which is subsequently metabolized to:
i. Catecholamines, which include DOPA, dopamine, norepinephrine, epinephrine.
ii. Melanin, which is a pigment produced as a complex combination of several molecules derived from Tyrosine metabolism.

d. Metabolic diseases in Tyr metabolism include:
i. Phenylketonuria (PKU), which is a defect in phenylalanine hydroxylase that leads to build-up of alternative byproducts (phenyllactate, phenylacetate, and phenylpyruvate).
ii. Tyrosinemias are defects in the mutli-step tyrosine degradation categorized as types I, II, and III that refer to the particular dysfunctional enzyme involved.

Question 41

BH4 is used as a cofactor for first degradation

Answer 41

a. Phe: Phenylalanine hyroxylase
b. Tyr: Tyrosine hyroxylase
c. Trp: Tryptophan hydroxylase

Question 42

The sulfer containing amino acids.

Answer 42

a. Two of the 20 amino acids contain sulfer.
1) Methionine–> Essential amino acid
2) Cysteine—> Non-essential amino acid, because it’s synthesized from Met.

b. Cysteine can form disulfide crosslinks with another cysteine to produce cystine.

Question 43

Cys is critical for forming disulfides

sulfur containing A.A

Answer 43

a. Disufide cross-links are critical for the stability of many proteins.
b. These include hormones, cytokines, receptors (i.e. extracellular).

Question 44

S-adenosylmethionine (SAM)

Answer 44

a. 1st step of Met degradation:
i. Methionine → SAM by the ATP-dependent reaction below.

b. Activated sulfer.
c. Also known as adoMet.

Question 45

Methionine degradation, cysteine synthesis

Answer 45

Summary:

Met + Ser = Cys

Question 46

S-adenosylmethionine (SAM)

Answer 46

a. Regeneration of methionine from
homocysteine (catalyzed by Methionine
synthase) requires TWO coenzymes:
 1) N5-methyl-tetrahydrofolate (THF)
 2) Vitamin B12

b. The methyl group is transferred from
THF to B12 to homocysteine.

Question 47

Disorders in sulfer amino acid metabolism

Answer 47

1) Hyperhomocysteinemia: low levels of folate, B6, & B12 (vascular disease).
i. Cysteine is now essential and treat with folate, B6, & B12.

2) Homocystinuria: defect in cystathionine-β-synthase (CBS) leads to mental retardation,osteoporosis, & vascular disease.
i. Cysteine is now essential.
ii. Can treat with Vit B6 to “force” CBS activity.

3) Cysteinuria : kidney stones (renal failure), due to defective in transporter of cysteine (& Ornithine, Lysine, Arginine) that leads to crystallization (in kidneys), treat with acetazolamide that makes cysteine more soluble.

Question 48

Homocysteine is bad

Answer 48

a. Vascular disease
 Autoimmune Disease (AD) where Hcy acts as a  pro-inflammatory molecule.

b. High Hcy leads to impaired wound healing
c. High Hcy correlated to cancer (Cervical Cancer)

Question 49

S-adenosylmethionine (SAM)
Charged Sulfer is highly reactive (“active sulfate”)
and SAM serves many biological roles. For example

Answer 49

Methylation via SAM-dependent enzymes act on proteins, nucleic acids, lipids, carbohydrates.
Reviews by Cheng & Roberts.

•Epigenetics, host defense.
Goll & Bestor (2005) Annu.Rev.Biochem 74, 481-514.

•Cancer (methylation/demethylation of DNA)
Wilson et al. (2007) Biochem. Biophys. Acta. 1775: 138-162

•High levels of Met and SAM critical in maternal diet.
Rees et al. (2006) J Nutr. Jun;136(6 Suppl):1701S-1705S

•SAM may help treat depression.
Papakostas et al. (2003) Curr Psychiatry Rep. Dec;5(6):460-6.

Question 50

1-carbon transfer

Tetrahydrofolate (THF)

Answer 50

a. THF is produced from vitamin B9 (Folic acid) by Dihydrofolate reductase (DHFR) in two reactions.
b. THF is essential for synthesis of amino acids & nucleic acids.

Question 51

Glutathione (GSH)

Why is GSH important??

Answer 51

a. GSH is a highly soluble tripeptide as opposed to Cys.
b. As high as millimolar in some tissues.

c. Functions:
i) thiol acts as redox buffer (“SH buffer”) to maintain proteins in their
reduced forms (i.e. intracellular proteins) and regulate activity (i.e. enzymes).
ii) Cofactor for several enzymes (i.e. Glutathione transferase, GST).
iii) Reduce hydrogen peroxide (H2O2) to water and general protection against
ROS (radical oxidizing species).

Question 52

Glutathione (GSH)

In Red Blood Cells

Answer 52

a. GSH is important for Red Blood Cells (hemoglobin).
b. The heme iron must be ferrous (Fe2+) to bind O2.
c. Oxidation of heme, ferrous (Fe2+) –>ferric (Fe3+) cannot bind Oxygen.
d. GSH can keep the heme reduced for functional hemoglobin.

Methemoglobin (Fe3+) + GSH ——> hemoglobin (Fe2+) + GSSG

Question 53

Glutathione (GSH)
3 important enzymes related to GSH

(doubt we need to know this for the test)

Answer 53

1. Glutathione peroxidase: oxidizes GSH to GSSG.
   i. Mutations lead to higher breast cancer risk.
2. Glutathione reductase: reduces GSSG to GSH
   i. Mutations are rare, but especially problematic for RBCs (heme).
3. Glutathione S-transferase: conjugation of GSH to agents.
   i. Detoxification (ROS), drug resistance, upregulated in tumors (isoform piGST).

Question 54

Trp Metabolism

Answer 54

a. Trp metabolized to Pyruvate or acetyl-CoA.
b. Trp–> Serotonin,Melatonin,Niacin
c. Tetrahydrobiopterin cofactor (BH4).

From Trp we get:

i) Serotonin (neurotransmitter)
ii) Melatonin (hormone)
iii) Niacin (vit B3, energy, NAD)

Question 55

Phe & Tyr Metabolism

Answer 55

a. Phe—> Tyr (Phenylalanine hydroxylase).
b. Phe, Tyr metabolized to fumerate, acetoacetate.
c. Tetrahydrobiopterin cofactor (BH4).
d. Tyr–> catecholamines, melanin.

e. Diseases
i. Phenylketonuria (PKU), tyrosinemia I,II,III.
ii. Parkinson’s & depression, albinism.

Question 56

phenylketonuria (PKU)

Answer 56

PKU overview
•Common inherited disorder (1:10,000)
•Phe & Phenylpyruvate accumulate in blood
•Phenylpyruvate is reduced & decarboxylated.
•Phenylacetate has characteristic smell.
•Excreted in urine.