Conversion Of Amino Acids To Specialized Products and Purine/Pyrimidine Nucleotide Metabolism Flashcards

1
Q

Creatine

A

. Reserve of high-energy phosphate in muscle that can be rapidly mobilized to regenerate ATP from ADP during muscle contraction
. ADP + Cr-P ATP + Cr via creatine kinase

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2
Q

Creatine synthesis

A

. In kidney
. Guanidine group of Arg transferred to Gly forming guanidinoacetate (GAA)
. GAA brought to liver and methylated by S-adenosylmethionine to form creatine
. Brough to muscle

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3
Q

T/F small portion of total creatine is irreversibly cyclized to creatinine and excreted in urine

A

T

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4
Q

Urinary creatinine is estimate of ___

A

Muscle mass

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5
Q

Serum creatinine is measure of ____

A

Kidney function

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6
Q

S-adenosylmethionine

A

. Used in over 35 rxns as methyl donor
. Contains activated methyl group formed via condensation w/ ATP
. This can be used in methylation rxns catalyzed by methyltransferase enzymes

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7
Q

After methylation rxns. S-adenosylmethionine is converted to ___

A

Adenosylhomocysteine

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8
Q

How is methionine regenerated from homocysteine?

A

. Betaine from choline or 5-methyltetrahydrofolate as methyl donor (Vit. B12 dependent)
. Homocysteine then used to make cysteine or is excreted in urine

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9
Q

Nitric oxide and physiological mechanism

A

. Gas molecule
. Vasodilator, neurotransmission, immune function/inflammation
. Generated from guanidine nitrogen of Arg through nitric oxide synthase
. Formed in endothelial cells
. Diffuses into smooth muscles and binds to/stimulated gaunylyl cyclase
. Inc. cGMP and smooth muscle relaxation

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10
Q

NO isozymes

A

. Constitutive (cNOS)
. Inducible (iNOS)
. Neuronal (nNOS) in brains and nervous tissue as signaling molecule

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11
Q

Thyroid hormone synthesis

A

. Thyroxine (T4) and triiodothyronine (T3)
. Iodination and coupling of Tyr residues on prohormone thyrogobulin
. T4/3 proteolytically released from thyroglobulin is response to TSH

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12
Q

T3/4 functions

A

. Regulate metabolism

. Mediate thermogenesis

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13
Q

Iodine deficiency

A

Lack of iodine causes hypothyroidism and goiter

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14
Q

Melanin

A

. Formed via Tyr via enzyme tyrosinase as shown below
. Synthesized in skin
.

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15
Q

Albinism

A

. Results from deficiency of tyrosinase in melanocytes

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16
Q

Catecholamine neurotransmitters

A

. From Tyr
. Sequentially L-dopa, dopamine, NE, and epinephrine
. NE and E are regulators of carb, protein, and lipid metabolism

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17
Q

DOPA-decarboxylase is ____ dependent

A

B6

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18
Q

Conversion of dopamine to NE rxn

A

. Catalyzed by copper-containing enzyme dopamine beta-hydroxylase
. Dependent on Vit. C (ascorbate)

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19
Q

Parkinson’s disease and treatment mechanism

A

. Dopamine neuron degeneration
. Uses L-dopa and DOP carboxylase inhibitor doesn’t cross BB to control symptoms
. L-dopa taken up by neurons and converted to dopamine by DOPA-decarboxylase
. Carbidopa minimizes decarboxylation of L-dopa in liver and other tissues outside of brain
. MAO and COMT inhibitors help too

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20
Q

Catecholamines are inactivated by ____

A

. Oxidative deamination
. O-methylation
. Also inactivate serotonin

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21
Q

MAO inhibitors

A

. Antidepressant drugs that prolong NE and serotonin

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22
Q

Serotonin formation

A

. 2-step rxn involving hydroxylation (BH4 dependent) and decarboxylation (B6 dependent) of Trp

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23
Q

Melatonin formation

A

. In pineal gland
. Serotonin converted
. Involved in entrainment of circadian rhythm

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24
Q

Gamma-aminobutyric acid (GABA)

A

. Glu synthesized from direct amidation w/ ammonia or transamination of alpha-ketoglutarate
. Glu decarboxylated by Glu decarboxylase (GAD) to form GABA

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25
Q

GABA shunt

A

. GABA stored in vesicles
. Released into synapse
. Acts on GABA receptors for inhibitory action potential
. Uptakes through GABA transporters around neurons
. Metabolized through transamination into succinic semialdehyde catalyzed by GABA-transaminase

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26
Q

Acetylcholine formation

A

. Formed by Ser by sequential decarboxylation, methylation, and acetylation

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27
Q

Histamine

A

. Vasodilator
. Formed by decarboxylation of His
. Secreted from mast cells in response to inflammatory and allergic rxns

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28
Q

Antihistamine drugs

A

. Modulators of allergic responses from inc. histamine secretion

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29
Q

Activated precursors of DNA and RNA

A

. nucleotides

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30
Q

Activated intermediates in biosynthesis

A

. UDP-glucose in glycogen synthesis
. Adenosyl methionine in methyl-transfers
. CDP-alcohol in membrane phospholipid biosynthesis

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31
Q

Nucleotides in cellular communication and regulation

A

.cAMP as second messenger
. GTP/GDP
. ADP in blood clotting

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32
Q

Foods high in nucleotides

A
. Organ meats
. Anchovies 
. Yeast 
. Sardines
. Dark beer
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33
Q

T/F dietary nucleotides are incorporated into DNA

A

F, they’re broken into Uric acid

34
Q

Dietary nucleotides in GI tract

A

. Broken down by stomach acid and enzymes (pancreatic phosphodiesterases, nucleases, and nucleotidases)
. Some used for ATP synthesis
. Most degraded/excreted, ribose or deoxyribose is metabolized

35
Q

Location of nucleotide biosynthesis

A

Cytoplasm of all tissues

36
Q

components of purine synthesis

A

. ATP
. amino acids Glu, Gly, Asp to provide nitrogen atoms and parts of carbon skeleton
. Folic acid (form is 10-formyl-tetrahydrofolate)
. Occurs in cytoplasm of all tissues
. Ring built bit by bit on ribose

37
Q

Components of pyrimidine

A
. ATP 
. Aspartic acid, Gln
. Folic acid
. Make sUMP
. UMP is modified to form pyrimidine nucleotides needed (CMP/TMP)
38
Q

Nucleotide salvage of purines and pyramidines

A

. Recycling of free bases that become separated from sugar

. Several enzymes that attach an activated ribose to free base

39
Q

Orotic aciduria

A

. Genetic disease of pyrimidine biosynthesis
. Autosomal recessive
. Low protein activity in pyrimidine synthesis
. Impaired ability to make cytosine, thymine, and uracil
. Accumulate orotic acid/orotate
. Symptoms: failure to thrive, macrocytic megaloblastic anemia, orotic aciduria
. Treatment: exogenous uridine (precursor to all 3 bases)

40
Q

Latch-Nyhan syndrome

A

. Genetic defect in purine salvage
. Affected enzyme: hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
. Catalyzes hypoxanthine + PRPP to IMP + pyrophosphate and guanine + PRPP to GMP and pyrophosphate
. X-linked, rare
. Symptoms: mental impairment, involuntary movements, self-mutilation, high uric acid levels, gout later in life

41
Q

Folic acid

A

. Water-soluble vit.
. Carries 1C units in enzymatic rxns
. Essential for rapid growth
. Structure: Pterin ring (p-aminobenzoate) and polyglutamate tail
. Named for oxidized form in pills, reduced derivatives are biologically active

42
Q

What foods are supplemented w/ folic acid

A

Breads and cereals

43
Q

Anti-folate chemotherapy

A

. Kills all cells, not just cancer
. Rapidly dividing cells killed first (gastric mucosa, hair follicle cells)
. Hair loss and vomiting side effects

44
Q

Fluorouracil drug

A

.inhibits thymidylate synthase by binding irreversibly
. Cells die by lacking thymidylate for DNA synthesis
.nontoxic substance that converts into toxic form in body (FdUMP)

45
Q

Methotrexate

A

. Folate analog for chemo
. Inhibits dihydrofolate reductase (DHFR)that furans H2folate + NADPH into H4folate
. Starves rapidly growing cell for folate

46
Q

Hydroxyurea

A

. Inhibits ribonucleotide reductase
. Enzyme makes all deoxyribonucleotides needed by cell
. Used for cancer and HIV treatment and sickle cell

47
Q

Ribonucleotide reductase rxn

A

. Nucleotide diphosphate + NADPH -> deoxy-nucleotide disphosphate
. Uses CDP, UDP, ADP, and GDP
.dATP powerful inhibitor
. Need NADPH

48
Q

Sulfa drugs

A

. Analogs of p-aminobenzoic acid
. Acts as substrate for folate biosynthetic enzyme incorporated into folate in bacteria
. Inhibits next step, bacteria starved for folate, dies
. Works bc bacteria can’t transport folate

49
Q

Purine and pyrimidine catabolism

A

. Break down pyrimidine ring into energy-yielding metabolites but not major energy pathway
. Can’t break down purine rings for ATP, they are converted to uric acid and excreted
. Pyrimidines broken down to acetyl CoA and succinyl CoA

50
Q

Severe combined immunodeficiency disease (SCID)

A

. Autosomal recessive disease in purine catabolism
. Adenosine deaminase (ADA) deficiency
. Don’t generate function B/T cells so people die by age 2
. Diagnosed by recurring infections, confirmed by measurement in blood
. Deoxyadenosine accumulates in blood and converted to dATP, ribonucleotide reductase inhibited, cells can’t divide

51
Q

SCID treatment

A

. Children isolated
. Bone marrow transplant w/ HLA identical donor
. Gene therapy potential

52
Q

Gout

A

. Chronic hyperuricemia w/ acute attacks of inflammatory arthritis from urate crystals in joints
. Affects 4% pop. And 50% develop arthritis in big toe, feet joints, or lower extremities
. Can have nephropathy from crystal damage to kidneys
. Diagnosed during 1st attack of inflammatory arthritis and confirmed by crystals in tissue sample

53
Q

High serum urate result of _____

A

. Too much uric acid production (excessive cellular breakdown)
. Too little uric acid excretion (excessive renal retention)

54
Q

Gout factors

A

. Age (old)
. Sex (more common in men, inc. in women after menopause)
. Weight (obese, high meat and alcohol)
. Drug use (drugs that inc. acidity of tissue, act as diuretic and dec. liquid uric acid is dissolved in, uric acid excretion inhibited)

55
Q

High serum urate lab levels

A

. Males over 7.0 (onset 30-50)

. Females over 6.0 (onset 50-70)

56
Q

Why is gout onset later in women?

A

Premenopausal estrogen levels cause inc. uric acid excretion from dec. urate reabsorption in kidney

57
Q

How urate crystals damage tissue

A

. Cells take up crystals by phagocytosis
. Cells rupture
. Lysosomal enzymes released into tissue to induce inflammatory response

58
Q

End product of purine catabolism

A

Uric acid

59
Q

In neutral pH, uric acid forms crystals of ___

A

Sodium urate

60
Q

In acidic pH, uric acid forms crystals of ___

A

. Uric acid

. Common in urine

61
Q

Alllopurinol

A

. Gout treatment for preventative for attacks
. Analog of xanthine and inhibits xanthine oxidase
. Converts xanthine oxidase to alloxanthine that inhibits enzyme even more
. Causes production of soluble compounds that are easier to excrete

62
Q

Febuxostat

A

. Prevents acute gout attacks
. Xanthine oxidase inhibitor
. Works better than allopurinol due to less drug interactions but is more expensive

63
Q

Probenecid

A

. Preventative treatment for gout

. Facilitates excretion of uric acid by blocking reabsorption in kidney

64
Q

Colchicine

A

. Used for acute gout
. Prevents and blocks inflammatory response that causes pain
. Binds to microtubules and prevents cell from phagocytosis crystals of uric acid

65
Q

Indocin

A

. Used for acute gout attacks

. Non-steroidal anti-inflammatory

66
Q

Elitek (rasburicase)

A

. Used to prevent gout int hose w/ tumor lysis syndrome
. People develop high uricemia from chemotherapy
. Genetically engineered form of enzyme uricase that converts uric acid to allantoin that is water soluble

67
Q

PRPP synthetase

A

. Used in purine biosynthesis
. Not committing step bc it is used in pyrimidine synthesis too)
. PRPP inhibited by purine nucleotide diphosphates and purine nucleotide triphosphates
. Activated by phosphate

68
Q

PRPP aminotransferase

A
. Regulatory step 
. Driven by hydrolysis of pyrophosphate 
. Inhibited by AMP, GMP, and IMP 
. Any small inc. in substrate will result in proportional inc. in enzyme activity 
. Sensitive to PRPP
69
Q

Mycophenolic acid

A

. Inhibitor of IMP dehydrogenase
. Impairs growth of rapidly dividing Band T cells
. Prevents graft rejection in transplant patients

70
Q

Synthesis of GMP requires ___

A

ATP

71
Q

Synthesis of ATP requires ____

A

GTP

72
Q

Synthesis of GMP inhibits ___

A

Conversion of IMP to XMP

. First step unique to GMP synthesis

73
Q

AMP inhibits conversion of __

A

. IMP to adenylsuccinate

. First stepunique to AMP synthesis

74
Q

Carbamoyl phosphate synthetase II

A

. Regulatory step in pyrimidine synthesis
. Inhibited by UTP
. Activated by ATP and PRPP
.

75
Q

Carbamoyl phosphate synthetase I cycle in, compartment tissue, amino donor, and anabolic or catabolic?

A

. Urea cycle
. Catabolic
. Mitochondria in liver
. Ammonia as donor

76
Q

Carbamoyl phosphate synthetase II cycle in, anabolic or catabolic, compartment tissue,, and amino donor

A

. Pyrimidine biosynthesis
. Anabolic
. Cytosol and all tissue
. Gln is donor

77
Q

Cytidylate synthetase

A

. Changes UTP to CTP

. Goes from UMP -> UDP -> UTP is different enzyme

78
Q

Ribonucleotide reductase

A
. UDP -> dUDP
. Broad substrate specificity 
. Makes all deoxyribonucleotides needed by cell 
. Needed NADPH
. DATP powerful inhibitor 
. Inhibited by hydroxyurea
79
Q

Thymidylate synthase

A

.dUMP -> dTMP

. Important in chemotherapy

80
Q

Purine salvage pathway

A

. HGPRT used to make IMP or GMP and pyrophosphate from PRPP and hypoxanthine (IMP) or guanine (GMP)
. APRT forms AMP and pyrophosphate from adenine and PRPP

81
Q

Pyrimidine salvage pathway

A

. Pyrimidine phosphoribosyltransferase used

. Makes pyrimidine nucleotide from pyrimidine base and PRPP

82
Q

Purine nucleoside phosphorylase deficiency

A
. Loss of T cell function 
. Normal B cells 
. Symptoms: recurrent infections in infancy and childhood
. Rare recessive mutation 
. Affects purine catabolism