Biochemistry: Biosynthesis And Degradation Of Amino Acids

Front 1

What are the general functions of amino acids?

Back 1

1. Protein synthesis
2. Metabolic energy
3. Biosynthetic products.

Front 2

What's the difference between positive and negative nitrogen balance?

Back 2

Positive: Nitrogen consumed is greater than nitrogen excreted. It implies net protein synthesis and happens when recovering from starvation, growth, or pregnancy.

Negative: Nitrogen consumed is less than nitrogen excreted. It implies mobilization of amino acids, tissue necrosis, or a poor quality diet from starvation, burns, or surgery.

Front 3

What are essential amino acids?

Back 3

Can not be made in our bodies.

Histidine (H)
Isoleucine (I)
Leucine (L)
Lysine (K)

Methionone (M)
Valine (V)
Phenylalanine (F)

Threonine (T)
Tryptophan (W)

(HILL MVP TT)

Front 4

Which amino acids should be essential?

Back 4

They cannot be synthesized at a rate to sustain growth.

Cyteine (from methionine) and Tyrosine (from phenylalanine) can be synthesized in the body but only if their precursors (which are essential amino acids) are present.

Arginine (from urea cycle) is considered "semi-essential" because the capacity for its synthesis is limited.

Front 5

Which amino acids are non-essential and what are their precursors?

Back 5

Alanine from pyruvate
Glycine from pyruvate
Asparagine from OAA
Aspartic acid from OAA
Glutamic acid from aKG
Glutamine from aKG
Proline from glutamate
Serine from 3PG

Front 6

How is glutamic acid synthesized from a-ketogluterate? Cofactor? Cofactor in reverse direction?

Back 6

Transamination reaction: an amino acid (alanine or aspartate) exchanges its amine group for the oxy group in aKG. The products are glutamate and pyruvate or OAA (from alanine or aspartate accordingly)

Vit B6 (pyridoxine)

Reverse reaction: Can be the exact reverse reaction OR...

Glutamate dehydrogenase uses NAD+ or NADP+

Front 7

How is glutamine synthesized from glutamic acid (glutamate)?

Back 7

Glutamine synthase + NH3.

Uses ATP --> ADP

Front 8

What enzyme removes free ammonia from glutamine?

Back 8

Glutaminase

(gln --> glu)

Front 9

How is alanine synthesized?

Back 9

Transamination reaction: Another amino acid exchanges its amine group for the oxy group in pyruvate, turning the pyruvate into alanine.

Vit B6 (pyridoxine)

Front 10

What methyl donor is an intermediate in the pathway for conversion of methionine to cysteine? What other non-essential amino acid is required for this pathway?

Back 10

Methyl donor: SAM, which is synthesized from methionine and ATP (all three PO4s are released)

Serine is also involved in this reaction.

Front 11

Which amino acid is a precursor for proline synthesis?

Back 11

Glutamate

Front 12

Which four carbon citric acid cycle intermediate is transaminated to and from aspartate?

Back 12

Oxaloacetate (OAA)

Front 13

What's the nitrogen source for aspartate --> aspargine?

What's the nitrogen source for conversion of glutamate to glutamine?

Back 13

From glutamine (turns into glutamate)


Glutamine is synthetized by the enzyme glutamine synthetase from glutamate and ammonia

Front 14

How do you turn serine --> glycine? Is it reversible? Vitamin cofactor? Active form?

Back 14

Enzyme: Serine hydroxymethyl transferase

Reversible

Tetrahydrofolate (THF) folic acid and B6 active form pyridoxal phosphate, PLP

Front 15

What is the purpose of amino acid catabolism during fasting?

Back 15

The carbon skeletons of amino acids can be used to create intermeidate steps necessary for energy production, to synthesize glucose or to synthesize ketone bodies. They can also be used to synthesize other amino acids and fatty acids. The TCA cycle receives the carbon skeleton for most amino acids.

Front 16

How is nitrogen removed from amino acids before catabolism of their carbon skeletons?

Back 16

Transamination, an alpha amino acid is turned into an alpha-keto acid, while the alpha-ketogluterate is turned into L-glutamate. Then nitrogen is released as ammonia using H2O, NADP+ or NAD+ and glutamate dehydrogenase to make alpha keto glutarate.

Front 17

Which amino acid carries nitrogen from muscle tissue to the liver?

Back 17

Alanine, via the alanine cycle.

Front 18

Can the liver consume branched chain amino acids?

Back 18

No, it lacks the necessary enzymes.

Front 19

What happens to branched chain keto acids (BCKA)?

Back 19

They enter the citric acid cycle to produce ATP

Front 20

What is the Alanine cycle?

Back 20

In the fasting state, degradation of muscle protein provides the carbon skeletons for liver gluconeogenesis.

The nitrogens produced by BCAA to BCKA (used in TCA cycle) is added onto pyruvate to form alanine, which is then carried to the liver. In the liver, the nitrogen is separated from alanine and enters the urea cycle, freeing up pyruvate, which through gluconeogenesis, is turned back into G6P and then Glucose, which is then transfered back to the muscles.

*No net glucose synthesis, nitrogen transported to liver for urea cycle.

Front 21

Which of the TCA cycle intermediates serve as an entry point for amino acid carbons?

Back 21

Pyruvate (not really TCA intermediate but it can go there

Acetyl-CoA
aKG
Succinyl-CoA
Fumarate
OAA

Front 22

Why is leucine considered to be ketogenic?

Back 22

It makes acetoacetate, precursor for ketone body synthesis.

Front 23

What is a glucogenic amino acid?

Back 23

One that can be converted for a glycolytic or TCA cycle intermediate.

Front 24

Is glutamate glucogenic?

Back 24

Yes

Front 25

What is the role of glutamate dehydrogenase in forming urea? Where is it located?

Back 25

Converts glutamate to aKG using NAD+ or NADP+, and water and releases an NH4 in a reversible reaction. ADP and GDP stimulates its reaction, and ATP and GTP inhibits this reaction.

Occurs primarily in liver and kidneys.

Front 26

What are the two steps in the urea cycle that happen in the mitochondria?

Back 26

1. Synthesis of carbamoylPO4 from CO2, NH4, 2ATP -->2ADP (synthase). Commited step and is stimulated by N-acetyl glutamate.

2. Carbamyl phosphate + ornithine --> citrulline (ornithine transcarbamoylase). Regulated.

Compartmentation in mitochondria prevents interference from pyrimidine synthesis by CPS II.

Front 27

What are the three steps in the urea cycle that happen in the cytoplasm?

Back 27

1. Citrulline + Aspartate --> Argininosuccinate. (argininosuccinate synthase). ATP --> AMP, where most problems occur.

2. Argininosuccitate --> arginine (arginiosuccinate lyase). Fumarate is a biproduct.

3. Arginine --> Ornithine + Urea (arginase)

Front 28

What's the source of ammonia for carbamoyl synthase I?

Back 28

Glutamate DH reactions or from transaminations.

Front 29

What is carbamoyl synthase II?

Back 29

Cytoplasmic enzyme that is needed for pyrimidine synthesis

Front 30

What reaction is catalyzed by ornithine transcarbamoylase? Where does it occur?

Back 30

Ornithine --> Citrulline

Mitochondrial matrix

Front 31

Where does citrulline react with aspartate and what enzyme catalyzes this reaction?

Back 31

Cytoplasm

Citrulline+Aspartate --> Arginosuccinate (arginosuccitate synthetase)

Front 32

Which are the energy requiring steps in the urea cycle? How many high energy bonds are consumed in the synthesis of one molecule of urea?

Back 32

Formation of carbamoyl phosphate (2ATP --> 2ADP)

Formation of arginiosuccinate (ATP --> AMP)

Four bonds

Front 33

What enzyme cleaves argininosuccinic acid and what are the products of the reaction? Where does this reaction occur?

Back 33

Argininosuccinate --> arginine and fumarate (argininosuccinate lyase)

Cytoplasm

Front 34

What happens to fumarate?

Back 34

Converted to malate, then to OAA, then to aspartate or citrate.

Front 35

Which enzyme releases urea from arginine and what are the products of the reaction? Where does this reaction occur?

Back 35

Arginase

Cytoplasm

Front 36

What is the short time regulation of the urea cycle? Long term?

Back 36

High protein meals produce large amounts of ammonia. N-acetylglutamate (formed from glutamate and acetylCoA) stimulates for CPS I (mitochondrial form). CPS II (cytoplasmic form) is not affected.

Long term: Gene activation for urea cycle enzymes during starvation.

Front 37

Under extreme starvation, are the urea cycle enzyme concentrations increased or decreased? Why?

Back 37

They would increase since they would be breaking down lots of protein for energy.

Front 38

Hyperammonemia

Back 38

More Severe

Deficiency at CPS-I or ornithine transcarbamoylase

Metabolite prior to block is elevated (e.g. argininosuccinic aciduria)

Encephalopathy, symptoms neurological in nature

Front 39

Hyperammonemia with secondary oroticaciduria

Back 39

Deficiency in ornithine transcarbamoylase

Excess carbamoyl PO4 leaks into cytoplasm, pushes pyrimidine pathway

Orotic acid excess not converted to UMP (Uridine monophosphate, ribonucleotide)

Front 40

Hyperammonemia treatment

Back 40

Conjugation with benzoic acid and phenylacetic acid, which is then excreted in urine

Metabolic pathways shift to replace glycine and glutamine

Low protein, alcohol free diet helps. Sterilization of GI tract by broad spectrum of antibiotics is helpful for patients with hepatic encephalopathy.

Front 41

What small molecule with an alkaline pK accumulates when the urea cycle is genetically impared? How does protein restriction help?

Back 41

Ammonia. Protein restriction reduces ammonia relase by bacterial urases in the GI tract.

Front 42

What is the amino acid component of hippuric acid and the steps involved in its synthesis?

Back 42

Glycine

Benzoate becomes conjugated with glycine to form hippurate, which is excreted in urine

Front 43

Why would you administer benzoic acid or phenylacetate to a patient? How old is the patient likely to be?

Back 43

Administer if patient has an enzyme deficiency that is present in infancy, or for advanced liver cirrhosis in older individuals.

Front 44

Which amino acids are converted to pyruvate?

Back 44

Alanine
Cysteine
Glycine
Serine
Threonine
Tryptophan

Front 45

How is glutamine synthesized and degraded?

Back 45

Glutamate + ammonia + ATP --> Glutamine (glutamine synthase)

Glutamine --> Glutamate + H2O (glutaminase)

Front 46

What's the interconversion of glycine and serine?

Back 46

Serine <--> Glycine (serine hydroxymethyl transferase) THF <--> Methylene-THF

Difference is a methyl group, which is picked up by THF

Provides a route from glycine to pyruvate.

Threonine conversion also produces glycine.

Front 47

Explain the type of metabolites produced during branched-chain amino acid (BCAA) degradation and how these metabolites enter the TCA cycle

Back 47

BCAA are transaminated into keto acids (BCKA), BCKA then are converted to CoA thioesters by multienzyme complexes similar to aKG and pyruvate DH complexes.

Valine and isoleucine --> succinylcoA (glucogenic)

Leucine --> acetoacetylcoA (ketogenic)

Front 48

What is maple syrup urine disease?

Back 48

Enzyme deficiency of BCKA dehydrogenase, builds up BCKA (alpha ketoacid products) that gives diapers a burnt sugar, maple syrup odor. Neurologic symptoms, precipitated by fever, infection

Front 49

What is methylmalonic aciduria?

Back 49

BCKAs are an additional source of propionylCoA. It feeds into the methylmalonic pathway. Excess spills into urine with either cobalamin deficiency or enzyme deficiency.

Front 50

What is the common route through which glutamine, proline, and arginine enter the TCA cycle?

Back 50

They are all degraded to glutamate, then glutamate is transminated to aKG.

Front 51

How does histidine get into the TCA cycle?

Back 51

Histidine --> --> FIGLU (histidase). Deficiency produces histidinemia.

FIGLU --> Glutimate, using THF. THF deficiency elevates urine FIGLU with oral histidine load.

Histidine --> Histamine in mast cells (decarboxylase)

Front 52

What is the clinical significance of FIGLU?

Back 52

FIGLU = formiminoglutamate (a metabolite of histidine degradation).

This is excreted in urine when there is a folate deficiency. THF is a formimino acceptor for the reaction from FIGUL --> Glutamate. False positives may occur if the patient lacks the formimino transferase enzyme. Enzyme deficiency is benign since FIGLU can be excreted through urine.

Front 53

Which amino acids can be converted to acetylCoA? What physiological conditions accelerates this conversion?

Back 53

Isoleucine and leucine. Hypoglycemia can accelerate this conversion because amino acids entering the TCA cycle can serve as precursors for glucose synthesis.

Front 54

What's a key reaction that allows amino acids to provide carbon skeletons for glucose synthesis?

Back 54

Deamination

Front 55

Methionine cycle

Back 55

Methionine --> SAM. Uses ATP

SAM --> SAH. Loses CH3

SAH --> Homocysteine. Loses adenosine.

Homocystine --> Methionine. CH3 gets added on from THF, uses B12 (cyanocobalmin)

Front 56

How does methionine convert to succinylCoA?

Back 56

Excess homocysteine is converted to succinylCoA by cystathionine synthase pathway.

Homocysteine + Serine --> Cystathionine (cystathionine synthase). Deficiency produces homocystinuria

Cystathionine --> PropionylCoA + Cystine

PropionylCoA --> MethylmalonylCoA

MethylmalonylCoA --> SuccinylCoA. Uses B12, blocked in methylmalonic acidemia.

Front 57

What is the structure of SAM (S-Adenosylmethionine) and it's metabolic function?

Back 57

SAM is methionine with a ribose and adenine bound to the S of methionine. It serves as a methyl donor.

Front 58

What molecule does ATP react to yield SAM?

Back 58

Methionine

Front 59

What adenosyl containing molecule is produced when SAM donates its carbon?

Back 59

SAH (s-adenylhomocysteine)

Front 60

What are some molecules that require donations from SAM in their synthesis?

Back 60

Epinephrine
Choline
Creatine
Nucleotides
Melatonin

Front 61

How is homocysteine converted to methionine?

Back 61

Through the addition by methyl-THF and B12.

Front 62

What is homocystinuria?

Back 62

Cystathionine synthase deficiency.

Folate and or cobalmin (B12) deficiency.

Elevated serum homocystines is atherosclerosis risk factor.

Front 63

What is folate polyglutamylation?

Back 63

Folate is trapped in the cell by a polyglutamate "tail"

Methotrexate (folate analog, cancer drug) also polyglutamylated.

Front 64

What is methyl trap in B12 deficiency?

Back 64

Methyl folate cannot convert to other forms. All folate can be tied up as methyl folate.

Front 65

How are catecholamines, tyrosine and melanin synthesized from phenylalanine?

Back 65

Phenylalanine --> Tyrosine --> DOPA --> Melanin, or Catechoamines.

Tyrosine --> Homogentisate --> --> Fumarate + Acetoacetate

Phenylalanine --> --> Phenylacetate, Phenylpyruvate Phenyllactate. These metabolites build up if phenylalanine hydroxylase does not work.

Front 66

What is the metabolic defect that produces alkaptonuria?

Back 66

Deficiency in homogentisate oxidase

Excretion of homogentisate in urine (black urine)

Benign

Enzyme is used in catabolism of tyrosine

Homogentisate --> --> Fumarate + Acetoacetate

Homogentisate also deposits in cartilage (ochronosis), affects the vetebral column, back pain by age 30, joint replacements by age 50.

Front 67

What is the synthesis of DOPA from phenylalanine?

Back 67

Phenylalanine --> Tyrosine (phenylalanine hydroxylase). Requires NADPH and BioH4 --> BioH2

Tyrosine--> DOPA

DOPA forms catecholamines and melanin.

Front 68

PKU

Back 68

Deficiency in phenylalanine hydroxylase.

Builds up phenylpyruvate, phenylacetate, phenyllactate.

Mental retardation. Neurotoxic before age 6 because of developing brain. At adolescence, brain becomes insensitive to altered metabolism in PKU. Treated by dietary restriction of phenylalanine.

Front 69

Inherited enzyme deficiencies

Back 69

Intermediates in blocked pathways can increase flow into other pathways or spill into the blood. Incompletely degraded macromolecules can accumulate in lysosomes or spill into the blood.

Front 70

PKU I vs. PKU II

Back 70

I: Blocked phenylalanine --> tyrosinase (phenylalanine hydroxylase)

II: Blocked biopterin reductase (BH4-->BH2 by NADPH-->NADP)

This is the malignant form, that still results in brain damage even in low phenylalanine diet because of biopterin reductase deficiency. This enzyme is needed for neuro transmitters.

Front 71

What produces serotonin? Melatonin? What is the amino acid precursor?

Back 71

Tyrptophan --> 5hydroxytroptophan --> serotonin --> melatonin

Seratonin: Produced in the brain, pineal gland, chromaffin cells in the gut. Peripheral vasodialation, neurotransmitter.

Melatonin: Produced in the pineal gland, converted from serotonin.

Front 72

How is carnitine synthesized?

Back 72

From lysine.

Trimethyllysine (modified lysine) is cleved from protein, pathway requiring ascorbate (methyl donor) and iron produces carnitine.

Deficiencies in carnitine production produces myopathic (muscle only) or systemic symptoms.

Front 73

What is Niacin synthesized from?

Back 73

Tryptophan

A part of the degradative pathway. Not sufficient for minimum daily requirement

Front 74

Cystinuria

Back 74

Impared reabsorption of dibasic amino acids in kidney and intestinal lumen.

Lysine, arginine, ornithine, cystine (cys-S-S-cys)

Kidney stones from cystine

Defective membrane transporter.

Front 75

Hartnup disease

Back 75

Defective intestinal absorption of tryptophan and niacin

Pellagra symptoms: Dermatitis, neurological.

Front 76

What are the precursors for creatine?

What is the function of creatine phosphate?

Back 76

Derived from arginine, glycine, SAM.

Creatine (phosph)kinase (CPK), reversible phosphorylation by ATP, energy storage.

ATP is generated in contracting muscle by the reversible creatine kinase reaction. This is only for the first few seconds of contraction.

Front 77

What is creatinine and how is it different from creatine?

Back 77

Creatine phosphate is nonenzymatically degraded into creatinine (PO4 released). Creatinine is utilized in urinalysis as a test of glomerular filtration rate (GFR)

Front 78

What is the function and precursors for mealanin?

Back 78

Functions as a UV sponge. Tyrosine absorbes UV light (aromatic rings). Melanin is polymerized doqaquinone; a potent UV screen.

Melanosomes are localted distal to the nucleus, absorbs UV radiation before reaching DNA.

Front 79

What is the function and precursors for melatonin?

Back 79

From tryptophan, functions as a regulator of sleep cycles

Front 80

Where is melanin synthesized? How is this related to its function?

Back 80

Melanin is synthesized by melanosomes, which are located distal to the nucleus. They are on the outer portion (the sunny side) of the cell. This way, UV light is absorbed before it can reach DNA.