Biochemistry Exam Iii - Amino Acids

Front 1

- Phosphoglycerate
- Pyruvate
- Oxaloacetate
- alpha-ketoglutarate

Back 1

Nonessential amino acids are derived from these glycolytic and TCA intermediates

Front 2

- Pyruvate
- a-KG
- Fumarate
- Oxaloacetate
- Succinyl CoA

- Acetyl CoA
- Acetoacetate

Back 2

7 metabolic intermediates derived from the 20 amino acid degradation

Front 3

______ can be synthesized from the glycolytic intermediate 3-phosphoglycerate.

3-PG is oxidized, trasaminated by glutamate, and dephosphorylated

Back 3

Serine

Front 4

_____ and ______ can be derived from serine.

Back 4

Glycine and cysteine

Front 5

________ can be produced from serine by a reaction in which a methylene group is transferred to tetrahydrofolate (FH4)

Back 5

Glycine

Front 6

_______ derives its carbon and nitrogen from serine.

The essential amino acid methionine supplies the sulfur

Back 6

Cysteine

Front 7

_______ can be derived by transamination of pyruvate

Back 7

Alanine

Front 8

_______ can be derived from oxaloacetate by transamination

Back 8

Aspartate

Front 9

______ is produced from aspartate by amidation

Back 9

Asparagine

Front 10

______ is derived from alpha-ketoglutarate by the addition of NH4+ via the glutamate dehydrogenase reaction or by transamination.

Glutamine, proline and arginine can be derived from _________

Back 10

Glutamate

Front 11

__________ is produced by amidation of glutamate

Back 11

Glutamine

Front 12

_______ and ________ can be derived from glutamate semialdehyde.

GS is formed by reduction of glutamate

Back 12

Proline and arginine

Front 13

______ can be produced by cyclization of glutamate semialdehyde

Back 13

Proline

Front 14

_________, via three reactions of the urea cycle, can be derived from ornithine, which is produced by transamination of glutamate semialdehyde

Back 14

Arginine

Front 15

________ is syntehsized by hydroxylation of the essential amino acid phenylalanine in a reaction that requires tetrahydrobiopterin.

Back 15

Tyrosine

Front 16

- Lysine
- Isoleucine
- Threonine
- Tryptophan

Back 16

These four amino acids can form acetyl CoA.

Front 17

- Phenylalanine
- Tyrosine

Back 17

These amino acids can form acetoacetate

Front 18

Leucine

Back 18

Degraded to form HMG-CoA, which can be turned into acetoacetate or acetyl-CoA.

Front 19

- Threonine
- Isoleucine
- Methionine
- Valine

Back 19

These four amino acids form Propionyl CoA

Propionyl CoA -> Methylmalonyl CoA -> Succinyl CoA

Front 20

This carrier of one-carbon groups transfers the most oxidized form, from CO2

Back 20

Biotin

Front 21

- Tetrahydrofolate (FH4)
- Vitamine B12
- S-adenosylmethionine (SAM)

Back 21

Transfers one-carbon units less oxidized than CO2

Front 22

_______ is the primary one-carbon carrier in the body.

Attachment of these one-carbon groups to ___ are referred to as the one-carbon pool.

Back 22

Tetrahydrofolate, FH4

Front 23

Methotrexate is used in cancer chemotherapy to block nucleotide synthesis, (which involve FH4 derivatives), especially the formation of thymidine.

It is also used to treat various forms of arthritis

Back 23

Medicinal uses of Methotrexate.

Blocks reduction step of DHF reductase.

Methotrexate is an analog of dihydrofolate (thus, it is a competitive inhibitor of dihydrofolate reductase)

Front 24

This is the only non-essential amino acid that is glucogenic and ketogenic

Back 24

Tyrosine

Front 25

- Isoleucine
- Threonine
- Phenylalanine
- Tryptophan

Back 25

Essential amino acids that are ketogenic and glucogenic

Front 26

- Histidine
- Methionine
- Valine

Back 26

Essential amino acids that are glucogenic only

Front 27

- Leucine
- Lysine

Back 27

Essential amino acids that are ketogenic only

Front 28

1. Active form is tetrahydrofolate (FH4)

2. FH4 - carries the one carbon pool

3. Required in diet

4. Deficiencies seen in alcoholics

5. Deficiencies in pregnant women - risk of neural tube defects

Back 28

Folic acid

Front 29

- Serine (major source)
- Glycine
- Histidine (via FIGLU)
- Tryptophan (via formate)

Back 29

Sources of 1-carbon units

Front 30

- dTMP
- Serine, derived from Glycine
- Purines
- B12-CH3

Back 30

Recipients of 1-carbon units

Front 31

1. Required in the diet (Liver stores up to 6 years supply)


2. Active part is the cobalt atom coordinated to the corrin ring
- Reacts with carbon of a methyl group (methylcobalamin)
or deoxyadenosine (deoxyadenosylcobalamin)

3. Two reactions in the body:

a. Rearranges the methyl group of methylmalonyl CoA to form succinyl CoA
- Part of the degradation route for the conversion of carbons from:
- Valine
- Isoleucine
- Threonine
- Methionine

b. Transfers a methyl group to homocysteine forming:
- Methionine

Back 31

Vitamin B12 (Cobalamin)

Front 32

SAM is produced from methionine and ATP

Transfers methyl groups to precursors that form the following:

- Creatine
- Phosphatidylcholine
- Epinephrine
- Melatonin
- Methylated nucleotides

Back 32

S-Adenosylmethionine (SAM)

Front 33

Biological roles of _______ transaminase

1. Protein synthesis

2. Transports nitrogen from peripheral tissue to the liver (2nd highest circulating amino acid)

3. Major gluconeogenic amino acid - serves as a carbon source for glucose.

Back 33

Alanine Transaminase (ALT)

Favors Alanine and a-KG in muscle.

Favors pyruvate and glutamate in liver

Front 34

Major sites of serine synthesis?

Back 34

- Liver

- Kidney

Front 35

1. Protein synthesis
2. Component of:
a. phsphatidylethanolamine
b. phsphatidylserine
c. sphingolipids (PLP-dependent decarboxylation)
3. Serves as a carbon source for glucose
4. Synthesis of acetylcholine
5. Synthesis of cysteine
6. 1-carbon units
7. Synthesis of glycine

Back 35

Biological roles of serine

Front 36

Increased serine levels
- Repression of 3-phosphoglycerate dehydrogenase
- Serine inhibits phosphoserine phosphatase

Decreased serine levels
- Induction of 3-phosphoglycerate dehydrogenase
- Release of phosphoserine phosphatase inhibition

Back 36

Regulatory mechanisms of body serine levels.

Note: most protein regulation is similar to this.

Front 37

- Serine and its metabolites (pyruvate and glycine) are precursors to sphingolipids and phospholipids.

- SAM methylates phosphatidylethanolamine to produce phosphoatidylcholine

- Hydrolysis of phosphatidylcholine releases choline.

- Acetylation of choline generates acetylcholine

Back 37

Key points on specialized products from serine

Front 38

1. Protein synthesis
2. 1-Carbon pool
3. Synthesis of purines
4. Synthesis of porphyrins
5. Synthesis of glutathione
6. Synthesis of creatine
7. Sythesis of glycine conjugated bile salts

Back 38

Biological roles of glycine

Front 39

- Gly, Arg, SAM and ATP are used to make creatine phosphate

- Kinase reaction is reversible

- Creatine and creatine phosphate are found in muscle and brain

Back 39

Synthesis of Creatine and Creatine phosphate.

Note: creatine phosphate is very high energy, so high that it is reversible to form creatine and ATP.

Front 40

- Creatinine has no known function

- The amount of creatine produced is related to muscle mass.

- The level of creatinine cleared by the kidneys is a measure of renal function

Back 40

Creatinine is the result of spontaneous creatine phosphate cyclization.

The ratio of compound/creatinine is measured for clinical use.

Front 41

- Absense of transamination reaction which converts glyoxalate back to glycine.

- Absence of TPP

- Results in renal failure

Back 41

Type I primary oxaluria

Causes build up of calcium oxalate, kidney stones.

Front 42

- Characterized by severe mental retardation and epilepsy.
- Patients often die in infancy.

Deficiency in glycine enzyme complex.
- Increase NT concentration along with formation of kidney stones.
- NT is inhibitory.

Back 42

Nonketotic hyperglycinemia

Treatment - sodium benzoate: reacts with glycine to form hipurate.

Front 43

1. Glutathione
2. Sulfur metabolism
3. Protein biosynthesis
4. Taurine
5. Taurine conjugated bile salts

Back 43

Biological roles of cysteine

Front 44

What is the major degradation destination for methionine and homocysteine?

Back 44

Degradation into Succinyl CoA

Front 45

In this environment, you are likely to find cysteine and homocysteine floating around.

Back 45

Intracellular / Reducing environment

Front 46

In this enviornment, you are likely to find cystine and homocystine floating around.

Back 46

Extracellular / Non-reducing environment

Front 47

- Group of disorders involving defects in the metabolism of homocysteine
- Autosomal recessive disorder
- High plasma and urinary levels of homocysteine
- High levels of methionine (cystathionine synthase or cystathionase)
- Low levels methionine (vitamin B12, folate, N10-methylene-FH4 reductase)
- Low levels of cysteine (vitamine B6, cystathionine synthase, cystathionase)

Back 47

Homocystinuria

Front 48

Vitamin B6 deficiency

Back 48

Homocystinemia

Front 49

Most common cause of homocystinuria is a genetic defect in ____________ synthase

Major clinical manifestations
- Lens dislocation
- Osteoporosis
- Mental retardation
- Vascular occulsions

Back 49

Defect in cystathionine synthase

Front 50

- Benign
- Due to increased Km for methionine.
- Increased met requirement.

Back 50

Hypermethioninemia

Front 51

Specialized Product - Comes from breakdown of what amino acid?

3'phospoadenosine-5'-phosphosulfate (PAPS)
- Transfers sulfate groups to biological molecules (sulfur metabolism)

Back 51

Product of cysteine breakdown

Front 52

1. Protein synthesis
2. Contributes 2nd nitrogen for urea formation
a. Accepts nitrogen from glutamate via transmination reaction and eliminates nitrogen via arginino-succinate synthetase reaction.
3. Neurotransmitter
4. Precursor for synthesis of:
a: Asparagine
b. Purines
c. Pyrimidines

Back 52

Biological roles of aspartate

Liver favors aspartate formation.

Other tissues favor OAA and glutamate formation

Front 53

Some leukemic cells have lost the ability to synthesize asparagine.

What is the treatment?

Back 53

Supplementing with exogenous asparaginase.

Asparagine reacts via a deamidation reaction that hydrolyzes and cleaves off NH4+, forming aspartate.

Front 54

Amidotransferase reactions are unique in that they are always....

Back 54

irreversible and require ATP

Front 55

The only amino acids to undergo deamidation reactions

Back 55

Asparagine and glutamine

Front 56

- Aspartate (minor)
- Tyrosine
- Phenylalanine

Back 56

Amino acids that produce fumarate

Front 57

- Protein biosynthesis
- Production of tyrosine

Back 57

Two fates of phenylalanine

Front 58

- Required for rign hydroxylations (ie. Tyrosine and neurotransmitters)

- Synthesized from GTP

Back 58

Tetrahydrobiopterin (electron carrier)

Front 59

1. Protein biosynthesis
2. Precursor of:
a. melanins
b. catecholamines
c. thyroid hormones
Tetraiodothyroinine (T4) and Triiodothyronine (T3)
i. Secreted by thyroid acinar cells
ii. Control rate of oxidation in cells

Back 59

Biological roles of tyrosine

Front 60

- Enzymes responsible for inactivation and degradation of catecholamines.
- reactions can occur in any order
- Final products:
a. 3-methoxy-4-hydroxymandelic acid (epinephrine, norepinephrine)
b. Homovanillic acid (dopamine)

Back 60

Monoamine oxidase (MAO)and Catechol-O-methyltransferase (COMT)

Front 61

Complex mixture of biopolymers derived from tyrosine.
Produced in melanocytes
Passed to surrounding keratincytes.

Back 61

Melanin

Front 62

Eumelanin
- Brown and black pigments found in hair and skin (more abundant in peoples with dark skin)

Pheomelanin
- Cysteine derivatives of eumelanin and imparts a yellow to reddish hue (more abundant in fair-skinned peoples)

Back 62

Two broad categories of melanin

Front 63

What enzyme is responsible for conversion of tyrosine to melanin?

Back 63

Tyrosinase

Cofactor: Cu2+

Tyrosine -> DOPA -> Dopaquinone -> Melanin

Front 64

1. Protein synthesis

2. Eliminates nitrogen
a. Collects amino nitrogen via transamination reaction
- Predominant amino acid / a-ketoacid pair is glutamate/a-ketoglutarate
b. Urea formation
- Contributes 1st nitrogen to urea formation
- Contributes nitrogen to aspartate

3. Anabolic role
- Donates amino group for formation of other amino acids (transamination)

4. Excitatory neurotransmitter

5. Precursor for synthesis of:
a. glutamine
b. Proline
c. Arginine
d. Ornithine which gives rise to polyamines
e. Glutathionine, serves as a cellular reductant*
f. g-carboxyglutamate, critical amino acid of blood clotting proteins
g. g-aminobutyric acid (GABA), an inhibitory neurotransmitter
h. Purine

Back 64

Biological roles of glutamate

Glutamate and aspartate are excitatory neurotransmitters

Front 65

- Major inhibitory neurotransmitter in CNS

- GABA receptors are Cl- channels.

- Recycled neurotransmitter (remember, catecholamines are not!)

Back 65

GABA

Enzyme: Glutamate decarboxylase (PLP)

Vitamin B6 deficiency = Convulsions (glutamate requires PLP for decarboxylation)

Drugs (eg benzodiazepines) enhance the effects of GABA are useful for treating epilepsy and depression.

Front 66

Histidine is an essential amino acid.

Histidine -> FIGLU -> Glutamate

Back 66

Glutamate cannot form histidine.

Important because histamine is a key neurotransmitter.

Front 67

1. Made mainly in the liver

2. Protective reductant
a. Reduces radicals and peroxides

3. Conjugation reactions to detoxification

Back 67

Glutathione (y-glutamylcysteinylglycine)

Tripeptide composed of Glutamate, Cysteine and Glycine.

Remember that bond between cysteine and glutamate? are not peptide bonds

Front 68

1. Protein synthesis
2. Precursor of:
a. Asparagine
b. Purines and pyrimidines
3. Nitrogen transport
4. Source of ammonia for urea formation
5. Excretion of ammonia into lumen of the renal tubule to buffer the urine (major role of kidney glutaminase)

Back 68

Biological Roles of glutamine.

Glutamate (product of glutamine degradation) follows GNG pathway

Front 69

Essential in children.

Required to support growth

Adequate amounts are released to carry out the biological role in adults.

Back 69

Arginine (adult nonessential)

Arginine cleaved by arginase to generate urea and ornithine
- Ornithine levels higher than required for urea.
i. Converted to either glutamate or proline

Front 70

_____ _____ has been implicated in a wide range of physiological and pathphysiological events including vasodilation (smooth muscle)
a. Activates guanylyl cyclase leading to increases in [cGMP]

b. Sildenafil (Viagra): inhibits phosphodiesterase which converts
cGMP to GMP

Back 70

Nitric oxide

A signal molecule that comes from arginine and is converted to citrulline and NO.

Front 71

Production of this molecule is quite unusual.

- Essential when dietary arginine is low or arginine synthesis is lacking.

Precursor of citrulline and polyamines.

Back 71

Ornithine

(product of proline degradation)

Front 72

- Degradation of ______ is the reverse of synthesis and occurs in mitochondria.

- Glutamate is produced

- Different enzymes are used

- Some of the glutamate semialdehyde makes ornithine

Back 72

proline

Front 73

1. Protein synthesis
2. Precursor of hydroxyproline

Back 73

Biological roles of proline

Front 74

- Putrescine has a foul odor

- Spermidine and spermine were isolated from semen

- An early signal for cell replication is elevated levels of ornithine decarboxylase

- Polyamines are highly cationic and are important for DNA synthesis and regulation of the replication process.

- Polyamine synthesis is linked to SAM and SAM decarboxylase

- Polyamines regulate SAM decarboxylase activity

Back 74

Polyamines and their properties

Synthesis requires ornithine and SAM

Front 75

Since DNA is negatively charged, these molecules are thought to aid in replication based on their postive charge.

Back 75

Important property of polyamines

Front 76

- Acceptor of carbamoyl phosphate in the urea cycle

- Precursor for the synthesis of polyamines

- Precursor for the synthesis of citrulline, arginine and proline

Back 76

Roles of Ornithine

Production of ornithine from glutamate is unusual
- When dietary arginine is limited

Front 77

When arginine levels are high, ornthine will be produced.
- Ornthine levels rise and semialdehyde accumulates, which inhibits ornthine transaminase.

Back 77

Usual direction of ornthine transaminase is in the direction of glutamate semialdehyde.

Front 78

- Serine
- Threonine
- Histidine
- Glycine
- Methionine

Back 78

Deamination reactions

All occur in the liver

Front 79

Common compound found in skin and sweat.

Product of histidine breakdown.

Back 79

Urocanate

Front 80

Compound that donates carbons to FH4 pool

Folate deficiency, it gathers in the urine.

Back 80

FIGLU

It is the precursor to glutamate.

Front 81

- Synthesized and released by mast cells
- Mediator of allergic responses: vasodilatation and bronchoconstriction (H1 receptors)
a. H1 Blockers: Diphenhydramine (Benadryl), Loratidine (Claritin)

- Stimulates secretions of gastric acid (H2 receptors)
a. H2 Blockers: Cimetidine (Tagamet), ranitidine (Zantac)

Back 81

Histamine

Synthesized by Histidine decarboxylase (PLP)

Neurotransmitter

Front 82

Metal binding domain of:
- Hemoglobin
- Cytochromes
- Chlorophyll

Back 82

Porphyrins

Formed from succinyl CoA and Glycine

Front 83

What enzyme turns L-methymalonyl CoA into succinyl CoA?

Back 83

Methylmalonyl CoA mutase.

Vitamin B12 linked enzyme.

Turns a branched structure (methylmalonyl CoA) to an unbranched enzyme (succinyl CoA)

Front 84

Primary pathway for serine/threonine degradation.

Produces free NH3 - Source of ammonia for urea cycle

Back 84

Serine/threonine dehydratase.

PLP

Front 85

Branched Chain Amino Acid:

Generates:
- Succinyl CoA
- 3 NADH
- 1 FADH2

Back 85

Valine

Front 86

Branched Chain Amino Acid:

Generates:
- Acetyl CoA
- Succinyl CoA
- 3 NADH

Back 86

Isoleucine

Front 87

Branched Chain Amino Acid:

Generates:
- Acetyl CoA and acetoacetate.
- 1 NADH
- 1 FADH2

Back 87

Leucine

Front 88

Catabolism of BCAAs (Val, Iso, Leu) is carried out by almost all tissues

- 25% of the amino acids of a protein are BCAA

Energy generation

BCAAs can be converted to TCA intermediates

Major precursors of glutamine.

Back 88

Importance of BCAA's.

Brain:
- BCAA's produce glutamine, a source of nitrogen for neurotransmitter synthesis during fasting.

Front 89

Roughly 20% of the ATP supply in a resting muscle comes from BCAA oxidation

- Synthesizes glutamine, which effluxes from the muscle

a. Highest rate of BCAA oxidation occurs under conditions of acidosis

b. Glutamine production and its degradation in the kidney increase pH

Back 89

Skeletal muscle BCAA catabolism.

Front 90

Tryptophan reduces the dietary requirement of niacin

Insufficient dietary levels of niacin and Trp result in _______.

Symptoms are:
- dermatitis
- diarrhea
- dementia

Back 90

Pellegra

Front 91

- regulates sleep, mood & appetite (forms in brain)
- platelet aggregation & vasoconstriction (forms in platelets)
- smooth muscle contraction

Back 91

Serotonin's function as a neurotransmitter

Front 92

- Depression, migraines, schizophrenia & obsessive compulsive disorders

Back 92

Serotonin is used to treat these disorders

Front 93

The antidepressant, Prozac, inhibits reuptake of ________, thereby prolonging the ______ presence in the synaptic cleft

Back 93

serotonin

Front 94

Produced by the pineal gland in response to light-dark cycle
blood levels rise at night.

Possible roles:
- Organizing seasonal and circadian rhythms
- Regulating reproductive functions

Back 94

Melatonin roles.

Defect in dihydrobiopterin reductase (nonclassic PKU) leads to decreased synthesis of serotonin and melatonin.

Front 95

Transamination of this amino acid does not require PLP.

Glutamate receives the episilon amine group.

Back 95

Lysine.

Front 96

This molecule is an intermediate of lysine catabolism

Back 96

Saccharopine

Front 97

On proteins – e-amino group of lysine is trimethylated

- When protein is hydrolysed, e-N-trimethyllysine is liberated

- e-N-trimethyllysine is converted to carnitine

Back 97

Carnitine is required for transport of fatty acids into mitochondria

Front 98

1. Amino acids are derived from dietary proteins, body proteins and amino acid biosynthesis

2. Amino acid NH3 is removed

3. Amino acid carbon skeleton is converted inot a major metabolic intermediate

4. Amino acids are used to synthesize nitrogen-containing compounds.

Back 98

Properties of amino acids

Front 99

- Essential amino acids come from the diet.

- Amino acids are not stored

- Requirements of amino acids
a. Protein synthesis
i. Proteins are essential for body function
b. synthesis of other biomolecules (precursor function)
c. Major carbon source for gluconeogenesis
i. High protein and low carbohydrate intake
ii. Fasting, not prolonged fasting

- Excess amino acids are degraded.

- Defects in amino acid metabolism lead to many metabolic disease

Back 99

Metabolism of amino acids