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Diana's Flashcards > biochem exam 5 > Flashcards

biochem exam 5 Flashcards

1
Q

what are the three classes of genetic disorders that affect metabolic pathways?

A

lysosomal storage, toxin-generating, and energy production

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2
Q

what is lysosomal storage disorder?

A

caused by deficiencies in lysosomal enzymes or function –> substrates will accumulate over time, leading to swollen lysosomes and impaired cell structureand function

most LSDs present after 2-3 months of age and involve PROGRESSIVE DEGENERATION of neurologic function and skeletal deformities –> enzyme replacement therapy is used as treatment

ex: I-cell disease, Pompe disease, Gaucher, Tay-Sachs, Niemann-Pick

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3
Q

what is toxin-generating disorder?

A

result in accumulation of toxic substances –> treatment = avoiding unnecessary activation of affected pathway and/or inactivating or eliminating toxin

ex:
neurotoxin-generating: urea cycle defects, phenylketouria, maple syrup disease, organic acidurias, Refsum disease

other toxin-generating: G6PDH deficiency, hereditary fructose intolerance, galactosemia, dyslipidemias, primary oxaluria, homocystinuria

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4
Q

what is energy production disorder?

A

results in FASTING hypoglycermia, few are limited to muscle metabolism and result in muscle weakness with little or no association with faster metabolism (very FEW affect both fed and fasting metabolism, like pyruvate kinase deficiency in erythrocytes)

treatment = avoiding precipitating events (fasting, illness, exercise), ACUTE decompensation is treated by administration of IV glucose (to go back to fed state), some disorders of fasting metabolism become less severe as one reaches adulthood

ex: glycogen storage disorders (EXCEPT Pompe disease), defects in gluconeogenesis, MCAD deficiency

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5
Q

what are the 4 carbon non-essential AAs?

A

asparagine and aspartate (differ by one amide group)

OAA –> asp –> asn

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6
Q

what are the 2 or 3 carbon non-essential AAs?

A

glycine, serine, cysteine, and alanine

glucose –> 3-phosphoglycerate –> serine <–> glycine and serine –> cysteine, 3-phosphoglycerate –> 2-phosphoglycerate –> pyruvate <–> alanine

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7
Q

what are the 5 carbon non-essential AAs?

A

glutamine, glutamate, proline, anf argnine

citrate –> isocitrate – alpha-KG <–> glutamate –> glutamine or glutamate –> glutamate semialdehyde –> proline and arginine

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8
Q

what do glucogenic AAs produce?

A

pyruvate or TCA intermediates
use for gluconeogenesis

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9
Q

what to ketogenic AAs produce?

A

acetyl CoA

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10
Q

what AAs are ONLY ketogenic?

A

lysine and leucine

some AA may appear in both groups like tyrosine

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11
Q

how are the 2-3 carbon non-essential AAs degraded?

A

glucose <–> 3-phosphoglycerate which can convert to serine <–> glyine, serine –> 2-phosphoglycerate, or serine –> cysteine

2-phosphoglycerate + cysteine –> pyruvate <–> alanine

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12
Q

what is ser made?

A

from 3-PG and degraded to 2-PG

begins with oxidizing alcohol side chain of 3-PG to ketone making alpha-keto acid –> transamination making alpha-AA –> hydrolysis of phosphate –> SERINE –> transamination –> reduction –> phosphorylate –> 2-PG

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13
Q

how is serine gly made?

A

it is interconverted with ser by SERINE HYDROXYMETHYLTRANSFERASE and can also be degraded by glyoxylate pathyway or glycine cleavage enzyme

serine <–> glycine via serine hydroxymethyltransferase, glycine –> CO2, NH4+, and methyl attached to tetrahydro-folate via glycine cleavage enzyme OR transaminase and D-AA oxidase –> glyoxylate –> oxalate

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14
Q

what are serine hydroxymethyltransferase and glycine cleavage enzyme important?

A

these reactions are important because they provide carbons for the cofactor tetrahydro-folate (B9)

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15
Q

what is the oxalate produced from glycine important?

A

it can precipitate with calcium and form kidney stones

about 40% of oxalate production in the body is via this reaction

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16
Q

what happens when there’s a deficiency in the pyruvate-alanine aminotransferase?

A

can lead to PRIMARY OXALURIA type I because transaminase is not converting glycoxylate back to glycine, instead glycoxylate will build up and form oxalate = kidney stones

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17
Q

what is calcium oxalate?

A

a strong irritant, contain need-like crystals that cause pain and edema after coming into contact with lips, tongue, oral mucosa, conjunctiva, or skin –> lasts up to 2 weeks

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18
Q

how is cys made?

A

made from serine with sulfur coming from methionine in form of homocysteine

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19
Q

what can a deficiency in cystathinone beta-synthase cause?

A

type 1 homocystinuria
patients will experience PREMATURE VASCULAR DISEASE with 25% dying from thrombic complications
signs = subluxation (dislocation) of lenses in eyes, mental retardation, and osteroporosis in childhood

20
Q

what is cys degraded?

A

catabolized to pyruvate and sulfate, also route for catabolism of met

  1. sulfyhydryl group oxidized to sulfinic acid then transmaionation with alpha-KG produces pyruvate, glutamate, and sulfite
  2. sulfite oxidized to sulfate which can be incorporated into PAPS or excreted in urine

serine + homocysteine –> cystathinone via beta-cystathionine synthetase using PLP as cofactor –> cystathionine –> cysteine + alpha-ketobutyrate via cystathionase using PLP as cofactor –> cysteine sulfinic acid –> sulfite –> sulfate –> PAPS or urine

note: alpha-ketobutyrate can be converted to propionyl CoA –> methymalonyl CoA –> succinyl CoA

21
Q

what is alanine made?

A

alanine aminotransferase of amino group from glutamate –> pyruvate

22
Q

how are glu, gln, pro, and arg made?

A

they’re all made from and degraded to alpha-KG

23
Q

what is the significance of his?

A

it is also degraded to alpha-KG, but CANNOT be synthesized by the body so it is an ESSENTIAL aa

HOWEVER, it is not rapidly degraded, so dietary requirements are low because it can be efficiently recycled

24
Q

how is glu and gln made?

A

glu is made from and converted to alpha-KG, gln is made from and converted to glu

glu <–> alpha-KG via GDH and aminotransferases

glu <–> gln via glutamine synthetase and glutaminase

25
Q

how is pro and arg made?

A

glutamate semialdehyde is an intermediate in synthesis and degradation of pro and arg

side chain of glut can be reduced to aldehyde –> glu semialdehyde –> semialdehydecan SPONTANEOUSLY CYCLIZE and be reduced to pro or ornithine via ornithine aminotransferase

via urea cycle, ornithine can be converted arg (undergo whole urea cycle to generate arg)

all processes are REVERSIBLE

26
Q

how is asp and asn made?

A

asp and asn are converted and made from OAA

OAA <–> asp via transamination using PLP
asp <–> asn via asparagine synthetase or reversed using asparaginase

asp –> asn uses N group from glutamine for transamination

this reaction is analogous to alpha-KG, glu, gln reaction

27
Q

how is fumarate formed?

A

asp, phe, and tyr generate fumarate during their catabolism
recall: fumarate can be generated in urea cycle from asp
phe and tyr are both degraded to fumarate and acetoacetate

28
Q

how is succinyl CoA formed?

A

met, thre, ile, and val are all degraded to succinyl CoA via propinyl CoA
recall: propionyl CoA is also made in oxidation of odd-chain FAs

conversion of propionyl CoA to succinyl CoA requires B7 (for propionyl CoA carboxylase) and B12 (for methylmalonyl mutase)

29
Q

what happens when there’s a deficiency in methylmalonyl mutase (B12 metabolism)?

A

results in methylmalonic acidemia (accumulation of methylmalonyl CoA, BCAA, thr, OCFA, VOMIT)

infants begin to develop symptoms when first introduced to solid foods of with first viral or bacterial increation (because this triggers fasting state which will result in protein metabolism)

treatment = low protein diet (decrease protein catabolism), often supplemented with B12 or carnitine

30
Q

what are met and thr degraded to?

A

they’re degraded to alpha-ketobutyrate which is converted to propionyl CoA

met –> homocysteine (add serine) –> cystathionine or thr –> alpha-ketobutyrate –> propionyl CoA

rxn of alpha-ketobutyrate –> propionyl CoA is catalyzed by pyruvate dehydrogenase and alpha-KG dehydrogenase (uses coenzymes TPP, lipoic acid, CoA, FAD, NAD+)

31
Q

how is met made from homocysteine?

A

via met synthetase using B12 and tetrahydrofolate

32
Q

what are the branched amino acids and what are they degraded to?

A

val, ile, and leu

VAL is degraded to propionyl CoA, ILE to propionyl CoA and acetyl CoA, LEU to acetyl CoA and acetoacetate also ONLY ONE OF TWO AAs THAT IS SOLELY KETOGENIC

about 20% of AA in proteins are branched chain, and BCAAs have lots of oxidizable carbon so they play a large role in ENERGY PRODUcTION in fasting state

33
Q

explain the reaction of BCCAs

A

val, ile, and leu are all firs transaminated and then undergo oxidative decarboxylation via branched chain alpha-ketoacid DH

deficiency in alpha-ketoacid DH results in MAPLE SYRUP URINE DISEASE

34
Q

what is the maple syrup urine disease?

A

MSUD is caused by deficiency in alpha-ketoacid DH

acute PRESENTATION occurs when protein catabolism INCREASES due to fasted metabolism to consumption of BCAAs

35
Q

what can alpha-ketoisocaproic acid trigger?

A

derived from leu and triggers neuronal apoptosis

leu, ile, and val complete with other large neutral AA (like phe and trp) for entry into brain –> leads to depletion of AA needed for neurotransmitter synthesis

36
Q

what are the treatments for MSUD?

A

based on prevention of acute episodes and remediation of neural AA deficits (reversal of catabolic state; IV glucose initially then high calorie intake)

prevention of acute episodes
- tight regulation of BCAA consumption
- weekly AA monitoring
- early detection and treatment of infections or other physiologic stresses

remediation of neural AA deficits
- supplementation with tyr, trp, met, phe, his, thr, gln

37
Q

what is organic aciduria?

A

inherited disorders caused by deficiencies in enzymes involved in AA carbon skeleton degradation

alpha-ketoacids accumulate and contribute to development of metabolic acidosis, hyperammonemia, and neurologic damage

38
Q

what is the presentation of organic aciduria?

A

acute presentation with metabolic compensation = vomiting, metabolic acidosis, hypoglycemia, hyperammonemia (some cases it’s caused by inhibition of N-acetylglutamate synthase which makes N-acetylglutamate that activates CPSI)

39
Q

what are the long-term consequences of organic aciduria?

A

developmental dlay, ataxia, heart, kidney, and pancreatic problems

40
Q

what are the treatments of organic aciduria?

A
  • restriction of triggering AA
  • avoidance of fasting and monitoring of illness
  • supplementation with carnitine or glycine to facilitate production and elimination of acid-conjugates
  • vitamin supplementation
  • treatment of hyperammonemia as needed
41
Q

what is the function of ketogenic AAs?

A

they produce acetyl CoA or acetoacetate

trp catabolism is complex – it can be converted to nicotinamide portion of NAD/P, it’s ketogenic (acetyl CoA) AND glucogenic (can be converted to alanine –> pyruvate –> glucose), also generate formate

lys –> acetyl CoA

thr has two metabolic routes – one generates propionyl CoA via alpha-ketobutyrate and another generates glycine and acetate/acetyl CoA

42
Q

what happens when there’s defects in phe and tyr catabolism?

A

associated with many diseases
phe is hydroxylated to tyr by PHENYLALANINE HYDROXYLASE –> deficiency in hydroxylase or cofactor (tetrahydrobiopterin) results in phenylketouria (PKU)

tyr aminotransferase also transaminates phe, explaining accumulation of phenylketone in PKU

43
Q

what is the function of homogenitsate oxidase?

A

phe –> tyr via phe hydroxylase –> hydroxyphenylpyruvate –> homogentisate via decarboxylation –> fumarate and acetoacetate via homogentisate oxidase

deficiency in homogentisate oxidase reulst in ALKAPTOURIA

44
Q

what is the difference between classic and nonclassic PKU?

A

classic = deficiency in phe hydroxylase
nonclassic = deficiency in cofactor tetrahydrobiopterin

45
Q

explain PKU

A

accumulated phe inhibits transport of other large hydrophobic AAs to brain, causing altered neurotransmitter synthesis leading to problems in PSYCHOMOTOR development

decreased synthesis of CATECHOLAMINES may cause mood disorders in older patients

phenypyruvate (phenyllactate and pneylacetate) , produced by transamination of phe, accumulates in serum and urine (musky or mousy odor)

tyr is precursor of melanin (lack of melanin results in albinism)

46
Q

what is the treatment for PKU?

A

restriction of dietary phe and sometimes supplementation with large hydrophobic AAs

nonclassical PKU can be treated with tetrahydrobiopterin which can also benefit some individuals with class PKU

47
Q
A

Diana's Flashcards (8 decks)

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