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

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

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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
GABA shunt
. 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
26
Acetylcholine formation
. Formed by Ser by sequential decarboxylation, methylation, and acetylation
27
Histamine
. Vasodilator . Formed by decarboxylation of His . Secreted from mast cells in response to inflammatory and allergic rxns
28
Antihistamine drugs
. Modulators of allergic responses from inc. histamine secretion
29
Activated precursors of DNA and RNA
. nucleotides
30
Activated intermediates in biosynthesis
. UDP-glucose in glycogen synthesis . Adenosyl methionine in methyl-transfers . CDP-alcohol in membrane phospholipid biosynthesis
31
Nucleotides in cellular communication and regulation
.cAMP as second messenger . GTP/GDP . ADP in blood clotting
32
Foods high in nucleotides
``` . Organ meats . Anchovies . Yeast . Sardines . Dark beer ```
33
T/F dietary nucleotides are incorporated into DNA
F, they’re broken into Uric acid
34
Dietary nucleotides in GI tract
. 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
Location of nucleotide biosynthesis
Cytoplasm of all tissues
36
components of purine synthesis
. 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
Components of pyrimidine
``` . ATP . Aspartic acid, Gln . Folic acid . Make sUMP . UMP is modified to form pyrimidine nucleotides needed (CMP/TMP) ```
38
Nucleotide salvage of purines and pyramidines
. Recycling of free bases that become separated from sugar | . Several enzymes that attach an activated ribose to free base
39
Orotic aciduria
. 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
Latch-Nyhan syndrome
. 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
Folic acid
. 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
What foods are supplemented w/ folic acid
Breads and cereals
43
Anti-folate chemotherapy
. Kills all cells, not just cancer . Rapidly dividing cells killed first (gastric mucosa, hair follicle cells) . Hair loss and vomiting side effects
44
Fluorouracil drug
.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
Methotrexate
. Folate analog for chemo . Inhibits dihydrofolate reductase (DHFR)that furans H2folate + NADPH into H4folate . Starves rapidly growing cell for folate
46
Hydroxyurea
. Inhibits ribonucleotide reductase . Enzyme makes all deoxyribonucleotides needed by cell . Used for cancer and HIV treatment and sickle cell
47
Ribonucleotide reductase rxn
. Nucleotide diphosphate + NADPH -> deoxy-nucleotide disphosphate . Uses CDP, UDP, ADP, and GDP .dATP powerful inhibitor . Need NADPH
48
Sulfa drugs
. 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
Purine and pyrimidine catabolism
. 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
Severe combined immunodeficiency disease (SCID)
. 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
SCID treatment
. Children isolated . Bone marrow transplant w/ HLA identical donor . Gene therapy potential
52
Gout
. 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
High serum urate result of _____
. Too much uric acid production (excessive cellular breakdown) . Too little uric acid excretion (excessive renal retention)
54
Gout factors
. 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
High serum urate lab levels
. Males over 7.0 (onset 30-50) | . Females over 6.0 (onset 50-70)
56
Why is gout onset later in women?
Premenopausal estrogen levels cause inc. uric acid excretion from dec. urate reabsorption in kidney
57
How urate crystals damage tissue
. Cells take up crystals by phagocytosis . Cells rupture . Lysosomal enzymes released into tissue to induce inflammatory response
58
End product of purine catabolism
Uric acid
59
In neutral pH, uric acid forms crystals of ___
Sodium urate
60
In acidic pH, uric acid forms crystals of ___
. Uric acid | . Common in urine
61
Alllopurinol
. 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
Febuxostat
. Prevents acute gout attacks . Xanthine oxidase inhibitor . Works better than allopurinol due to less drug interactions but is more expensive
63
Probenecid
. Preventative treatment for gout | . Facilitates excretion of uric acid by blocking reabsorption in kidney
64
Colchicine
. 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
Indocin
. Used for acute gout attacks | . Non-steroidal anti-inflammatory
66
Elitek (rasburicase)
. 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
PRPP synthetase
. 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
PRPP aminotransferase
``` . 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
Mycophenolic acid
. Inhibitor of IMP dehydrogenase . Impairs growth of rapidly dividing Band T cells . Prevents graft rejection in transplant patients
70
Synthesis of GMP requires ___
ATP
71
Synthesis of ATP requires ____
GTP
72
Synthesis of GMP inhibits ___
Conversion of IMP to XMP | . First step unique to GMP synthesis
73
AMP inhibits conversion of __
. IMP to adenylsuccinate | . First stepunique to AMP synthesis
74
Carbamoyl phosphate synthetase II
. Regulatory step in pyrimidine synthesis . Inhibited by UTP . Activated by ATP and PRPP .
75
Carbamoyl phosphate synthetase I cycle in, compartment tissue, amino donor, and anabolic or catabolic?
. Urea cycle . Catabolic . Mitochondria in liver . Ammonia as donor
76
Carbamoyl phosphate synthetase II cycle in, anabolic or catabolic, compartment tissue,, and amino donor
. Pyrimidine biosynthesis . Anabolic . Cytosol and all tissue . Gln is donor
77
Cytidylate synthetase
. Changes UTP to CTP | . Goes from UMP -> UDP -> UTP is different enzyme
78
Ribonucleotide reductase
``` . UDP -> dUDP . Broad substrate specificity . Makes all deoxyribonucleotides needed by cell . Needed NADPH . DATP powerful inhibitor . Inhibited by hydroxyurea ```
79
Thymidylate synthase
.dUMP -> dTMP | . Important in chemotherapy
80
Purine salvage pathway
. 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
Pyrimidine salvage pathway
. Pyrimidine phosphoribosyltransferase used | . Makes pyrimidine nucleotide from pyrimidine base and PRPP
82
Purine nucleoside phosphorylase deficiency
``` . Loss of T cell function . Normal B cells . Symptoms: recurrent infections in infancy and childhood . Rare recessive mutation . Affects purine catabolism ```

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