144 Bfcp2A Biochemistry Amino Acid Metabolism

Front 1

What disease results from an inheritied deficiency of neutral amino acid transporters?

Back 1

Hartnup disease

Front 2

What disease is caused by an inherited deficiency of the ornithine and cystine AA tranpsorters?

Back 2

cystinuria

Front 3

What are the essential amino acids?

Back 3

Phenylalanine Valine Threonine Tryptophan Isoleucine Methionine Histidine (Arginine) Leucine & Lysine

Front 4

What are the conditionally essential amino acis?

Back 4

Arginine Cysteine Glutamine Gycine Proline and Tyrosine

Front 5

What is glutathione synthesized from?

Back 5

glutamate, cysteine, and glycine

Front 6

Where is arginine synthesized?

Back 6

Partly in the intestinine (ornithine to citrulline) and partly in the kidney (& other organs) citrulline through a number of amino acids to arginine

Front 7

Why is arginine important?

Back 7

It affects metabolic, neurologic, and reproductive function and is a precursor to nitric oxide.

Front 8

How is arginine converted to NO?

Back 8

via nitric oxide synthase (citrulline is also produced and funnelled back to the TCA cycle), tetrahydrobiopterin is a cofactor and the reaction requires NADPH

Front 9

How is apartate synthesized?

Back 9

from oxaloacetate via apartate aminotransferase (ammoniacomes from glutamate, glutamate is produced in the reverse reaction using α-ketoglutarate as the α-keto acid and aspartate as the amine group donor (requires pyridoxal phosphate as a cofactor)

Front 10

How is asparagine synthesized and why is this clinically relevant?

Back 10

It is synthesized from aspartate via asparagine synthetase using glutamine as the nitrogen source. In leukemia, asparagine synthetase is methylate making asparagine a conditionally essentially amino acid (and its metabolism a good drug target).

Front 11

What is the precursor to serine?

Back 11

3-phosphoglycerate (a glyoclytic intermediate)

Front 12

How is glycine synthesized?

Back 12

Glycine is derived from cerine, ammonia, and carbone dioxide and requires folate deriviatives.

Front 13

How is cysteine derived?

Back 13

cysteine is derived from serine (but it's sulfur comes from methionine, therefore, it can become conditionally essential)

Front 14

What is the structure of glutathione?

Back 14

It is a tripeptide derived from glutamate, cysteine, and glycine. The middle cysteine moiety is importante because it is where the reductive power of glutathione is derived from (disulfide bond forms).

Front 15

What is classical PKU?

Back 15

It is an inborn error of metabolism (autosomal recessive) that is the result of phenylalanine hydroxylase deficiency. It leads to phenylalanine accumulation and is treated by low phenylalanine diets and supplemental amino acids. On the screening register.

Front 16

What is non-classical PKU?

Back 16

It is an autosomal recessive disease that is the result of dihydrobiopterin reductase deficiency. This deficiency prevents dihyrdrobiopterin from being reconverted to tetrahydrobiopterin which is a necessary cofactor in phenylalanine to tyrosine conversion via phenylalanine hydroxylase (also important with serotonin, norepinephrine and NO synthesis--a serious deficiency).

Front 17

Why is PKU harmful?

Back 17

Toxic compounds derived from phenylalanine are synthesized in a greater quantity via an aminotransferase than is normally seen in a healthy individual.

Front 18

Why is tyrosine important?

Back 18

It's a precursor to dopamine, norepinephrine, epinephrine and melanine (melanine is via tyrosinase rather than tyrosine hydroxylase). It is also an important component of thyroid hormones.

Front 19

What causes albinism?

Back 19

Tyrosinase deficiency. Some other complications include poor eyesight and extreme sensitivity to sunlight.

Front 20

Why is tyrosine important to the endocrine system?

Back 20

It is used to generate throxine (T4) and triiodothryonine (T3) via the modification of tyrosine residues of the thyroglobulin protein in the thyroid gland.

Front 21

When does complete oxidation of amino acids typically occur?

Back 21

In the postpriandal state; in the fasting state the body goes through great lengths to avoid breaking down protein (ketogenesis, etc.)

Front 22

What are the ketogenic (not strictly) amino acids?

Back 22

phenylalanine, tyrosine, tryptophan, leucine, lysine, isoleucine

Front 23

Which enzyme is shared via the anaplerotic reactions of the "I Want My MTV" amino acids and an intermediate in odd chain fatty acid degradation and what is the clinical significance of this enzyme?

Back 23

Methylmalonyl CoA mutase converts propionyl-CoA to succinyl-CoA in conjunction with coenzyme B12. An inheritied enzyme deficiency with this enzyme, an inability to convert vitamin B12 to the coenzyme form, or a nutritional deficiency in vitamin B12 ca all cause methylmalonic acidemia.

Front 24

What common enzyme is used to degrade the branched chain amino acids leucine, isoleucine, and valine?

Back 24

branched-chain α-keto acid dehydrogenase complex (multi-protein complex similar to pyruvate dehydrogenae and α-ketoacid dehydrogenase of the MTv anaplerotic pathway)

Front 25

What is the clinical significance of branched-chain α-ketoacid dehydrogenase?

Back 25

A deficiency in this enzyme leads to the accumulation of sweet smelling α-ketoacids excretion causing "maple syrup urine disease." It is on the Michigan Newborn Screening Program register. Treatment is protein restricted diet supplement with thiamin B1 for residual dehydrogenase complex.

Front 26

What amino acid catabolic enzyme is used as a chemotherapeutic treatment in some leukemias?

Back 26

aparaginase (asparagine is a conditionally essential amino acid in acute lymphoblastic leukemia cells)

Front 27

When is pyruvate converted to oxaloacetate for gluconeogenesis in the liver?

Back 27

under fasting, starvation, and uncontrolled diabetic conditions

Front 28

What are some of the key features of a disease caused by the accumulation of tyrosine crystals?

Back 28

Tyrosinemia II leads to the erosion of cornea, palms, and soles and is treated by a low tyrosine diet. It's cause is an inherited deficiency of tyrosine aminotransferase, an enzyme involved in the first step of tyrosine degradation requiring PLP as a cofactor.

Front 29

What is a rather benign disease that leads to the excretion of a tyrosine metabolite known as p-hydroxyphenylpyruvate?

Back 29

Tyrosinemia III is a very rare inherited deficiency of the p-hydroxyphenylpyruvate dioxygenase.

Front 30

Which tyrosine related disease leads to the excretion of a tyrosine metabolite that turns to a black color in the presence of oxygen?

Back 30

Alkaptonuria is a disease resulting from the inherited deficiency of homogentisate 1,2-dioxygenase. Accumulation of homogentisate also leads to accumlation in soft tissue (including the eye) and joints that leads to arthritis and disc calcifcations.

Front 31

Which tyrosine related disease is the most severe and often requires a liver transplant?

Back 31

Tyrosinemia I results from an inherited deficiency of fumarylacetoacetase. It is treated by a diet low in phenylalanine and tyrosine combined with a druge known as NTBC that actually inhibits p-hydroxyphenylpyruvate dioxygenase (like tyrosinemia III) and allows excretion of p-hydroxyphenylpyruvate, delaying the need for liver transplant.

Front 32

What is the nitrogen balance during periods of growth?

Back 32

positive beause synthesis > degradation

Front 33

What is the typical first step in amino acid and nucleotide degradation?

Back 33

the loss of an amino group

Front 34

How do aminotransferase typically work?

Back 34

They transfer an α-amino acid group form amino acid 1 to an α-ketoacid of amino acid 2?

Front 35

What is the most common recipient of of an amino group from an amino transferase?

Back 35

α-ketoglutarate (resulting in glutamate)

Front 36

What cofactor is needed for aminotransferases?

Back 36

PLP (vitamin B6)

Front 37

Which aminotransferases are important clinically and why?

Back 37

ALT (alanine aminotransferase)--is predominantly in the liver; high levels are observed with viral hepatitis, ischemic liver injury, toxin or drug-induced liver injury, prolonged hypotension, and acute heart failure. AST (aspartate aminotransferase)--similiar levels among liver, heart, and kidney but will be elevated in liver and kidney diseae with heart damage. High levels also indicate prolonged hypotension, acute heart failure, and myocardial infarction (used in conjunction with LDH and CK).

Front 38

What are some enzymes that release free ammonia?

Back 38

dehydratases (serine, threonine); lyases (histidine, phenylalanine, aspartate); deaminases (purines & pyrmidines)

Front 39

How is ammonia transported from extrahepatic tissues to liver?

Back 39

via the amino acids glutamine, alanine, and serine (primarily)

Front 40

What enzymes are important for releasing ammonia from glutamine in liver mitochondria?

Back 40

glutaminase & glutamate dehydrogenase

Front 41

What activates the first step of the urea cycle?

Back 41

n-acetylglutamate

Front 42

Where does arginine de novo synthesis occur?

Back 42

in the urea cycle

Front 43

Where does the urea cycle occur?

Back 43

in mitochondria and cytoplasm

Front 44

What's the first step of the urea cycle?

Back 44

Conversion of ammonia liberated by glutamate dehydrogenase to carbomoyl phosphate via carbomoyl phosphate synthetase I (CPSI).

Front 45

What does CPSI require as an activator?

Back 45

n-acetylglutamate

Front 46

What are the requirements for n-acetylglutamate production?

Back 46

an excess of acetyl CoA, adequate glutamate, and adequate arginine will allow acetylglutamate synthase to convert glutamate to n-acetylglutamate

Front 47

When is th urea cycle unregulated?

Back 47

during starvation and high protein diets

Front 48

What is needed to convert carbomyl phosphate into a substrate that can be exported to the cytosol?

Back 48

ornithine transcarbamylase is an enzyme that converts carbamoyl phosphate to citrulline for which there are mitochondrial transporters

Front 49

For which urea cycle enzyme is there an inherited deficiency that can affect the synthesis of arginine (ultimately making it essential)?

Back 49

arginosuccinate lyase (ASL)

Front 50

What amino acid is required for the synthesis of argininosuccinate from citrulline and how is it supplied?

Back 50

aspartate can come from cytosolic pools or be supplied via from the TCA cycle via conversion of oxaloacetate to aspartate by aspartate aminotransferase

Front 51

How is urea ultimately formed?

Back 51

from arginine via arginase (also liberating ornithine to be recycled through the cycle)

Front 52

What cycle do some cells have to synthesize NO from UREA cycle intermediates?

Back 52

the arginine-citrulline cylce

Front 53

What are some common features of urea cycle disorders?

Back 53

hyperammonemia, hyperglutaminemia, present as hyperammonemic encephalopathy in neonates (except ARG1 deificiency), autosomal recessive (except OTC deficiency which is X-linked, and most common)

Front 54

What are two major modes of ammonia production in skeletal muscle?

Back 54

amino acid metabolism and AMP deamination (during exercise)

Front 55

What treatments are used to reduce ammonia levels via alternate nitrogen waste pathways?

Back 55

benzoate (glycine) and phenylacetate (glutamine) allow ammonia from amino acids to be excreted via hippurate and phenylacetylglutamine

Front 56

How is ASL deficiency treated?

Back 56

with pharmacological amounts of arginine