Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FA13 Biochemistry > Biochem-02-Genetics_Nutrition > Flashcards

Biochem-02-Genetics_Nutrition Flashcards

1
Q

Codominance

A
  • both alleles contribute to the phenotype

* example: Blood groups A,B, AB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Variable expressivity

A
  • Phenotype varies among individuals with the same phenotype

* example: 2 patients with neurofibromatosis type 1 (NF1) may have varying disease severity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Incomplete penetrance

A
  • Not all individuals with a mutant genotype show the mutant phenotype
  • example: BRCA1 gene mutations do not always result in breat or ovarian cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Pleiotropy

A
  • One gene contributes to multiple phenotypic effects

* PKU causes many seemingly unrelated symptoms, from mental retardation, to hair and skin changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Imprinting

A
  • Differences in gene expression depend on whether the mutation is of maternal or parental origin
  • example: Prader-Willi (Paternal on chromosome 15) and Angelman’s (Maternal on chromosome 15) syndromes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Anticipation

A
  • Increased severity or earlier onset of disease in succeeding generations
  • example: Huntington’s disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Loss of heterozygosity

A
  • If a patient inherits or develops amutation in a tumor suppressor gene, the complimentary allele must also get delete/dumtated before cancer develops
  • This is not true of oncogenes
  • example: retinoblastoma and the “two-hit hypothesis”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Dominant negative mutation

A
  • A mutation that exerts a dominant effect even if there is still another functional copy
  • example: mutation of a transcription factor in its allosteric sit, which allows it to bind DNA but prevents the wild-type good factor from binding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Linkage disequilibrium

A
  • Tendency for certain aleles at 2 linked loci to occur together more often that expected by chance
  • measured ina population, not a family; often varies in different populations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mosaicism

A
  • when cells in the body differe in genetic makeup due to postfertilization mutations during mitosis
  • example: mutation in precursor of bone marrow stem cell leads to a hematologic mosaic individual
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Germ-line mosaicism (Gonadal mosaicism)

A

Mosaicism of an individual’s gametes, which can produce disease in its offspring that is not present in the individual itself

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Chimeric individual

A

Derived from different zygotes that fuse (as opposed to a mosaic, which is one zygote)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Heteroplasmy

A

Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Uniparental disomy

A
  • Offspring receives 2 copies of a chromosome from one parent and nocopies from the other
  • Heterodisomy (heterozygous) indicates a meiosis I error
  • Isodisomy (homozygous) indicates a meiosis II error, or postzygotic chromosomal duplication of one chromosome and loss of the other
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Hardy-Winberg population genetics

A
  • p^2 + 2pq + q^2 = 1
  • p + q = 1
  • assumptions: no mutation at the locus, no selection for a genotype, random mating, no net migration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Imprinting

A

• At some loci, only one allele is active and the other is inactive (imprinted/inactivated by methylatinon); when that single allele is inactivated there will be a disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Prader-Willi syndrome

A
  • Paternal allele is not expressed in a number of genes in chromosome 15
  • Leads to mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
  • Can also be due to uniparental disomy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Angelman’s syndrome

A
  • Maternal allele is not expressed in a number of genes in chromosome 15
  • Leads to mental retardation, seizures, ataxia, inappropriate laughter
  • Can also be due to uniparental disomy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Modes of inheritance

A
  • Autosomal dominant: often due to defects in structural genes; multiple generations
  • Autosomal recessive: Often due to enxyme deficiencies; usually only one generation; comonly more severe than dominant disorders
  • X-linked recessive: more severe/common in males
  • X-linked dominant
  • Mitochondrial inheritance: often due to failures in oxidative phosphorylation; variable expression due to heteroplasmy; all offspring of females affected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Hypophosphatemic rickets (vitamin D-resistant rickets)

A
  • X-linked dominant disorder
  • results in increased phosphate wasting at proximal tubule
  • results in rickets-like presentation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Mitochondrial myopathies

A
  • Groupe of rare mitochondrially-inherited disorders
  • result from mutations affecting mitochondrial function
  • Often present with myopathy and CNS disease
  • Muscle biopsy often shows “ragged red fibers”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Achondroplasia

A
  • Autosomal dominant
  • Cell-signaling defect of fibroblast growth factor receptor 3
  • results in dwarfism: short limbs, larger head, but trunk size is normal
  • associated with advanced paternal age
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Autosomal-dominant polycystic kidney disease (ADPKD) (adult polycistic kidney disease)

A
  • Autosomal dominant (the infantile form is recessive)
  • 85% of cases are due to mutation in PKD1 in chromosome 16
  • Always bilateral, massive enlargement of kidneys due to multiple large cysts
  • patients present with flank pain, hematuria, hypertension, progressive renal failure
  • associated with polycystic liver disease, berry aneurysms, mitral valve prolapse
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Familial adenomatouse polyposis (FAP)

A
  • Autosomal dominant
  • Mutations of APC gene in chromosome 5
  • Colon becomes covered with adenomatous polyps after puberty; progresses to colon cancer unless the colon is resected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Familial hypercholesterolemia (hyperlipidemia type IIA)

A
  • Autosomal dominant
  • Elevated LDL due to defective or absent LDL receptor
  • Heterozygotes (1:500) have cholesterol ~ 300 mg/dL; Homozygotes (very rare) have cholesterol ~ 700+ mg/dL, severe athersoclerotic disease early in life, and tendon xanthomas (classically in the achilles tendon); MI may develop before age 20
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Hereditary hemorrhagic telangiectasia (HHT) (Osler-weber-rendu syndrome)

A
  • Autosomal dominant disorder of blood vessels

* findings: telangiectasia, recurrent epistaxis, skin discolorations, arteriovenus malformations (AVMs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Hereditary spherocytosis

A
  • Autosomal dominant
  • Spheroid erythrocytes due to spectrin or ankyrin defect (which lead to membrane bleb formation)
  • Hemolytic anemia with increase MCHC
  • splenectomy is curative
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Huntington’s disease

A
  • Autosomal dominant
  • trinucleotide repeate disorder (GAG)n of gene in chromosome 4 {Hunting 4 food}
  • leads to depression, progressive dementia, choreiform movements, caudate atrophy, and decreased levels of GABA and Ach in the brain
  • symptoms manifest between the ages of 20 and 50
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Marfan’s syndrome

A
  • Autosomal dominant
  • mutation in fibrillin-1 gene
  • connective tissue disorder affecting skeleton, heart, and eyes
  • findings: tall with long extremitis, pectus excavatum, hypermobile joints, arachnodactyly (long, tapering fingers and toes)
  • cystic medial necrosis of aorta can lead to aortic incompetence and disecting aortic anneurysms
  • can have a floppy mitral valve
  • can get subluxation of lenses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Multiple endocrine neoplasias (MEN)

A
  • Autosomal dominant
  • Several distinc syndrome (1, 2A, 2B) characterized by familial tumors of endocrine glands
  • Can affect pancrease, parathyroid, pituitary, thyroid, and adrenal medulla
  • MEN 2A and 2B are associated with ret gene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Neurofibromatosis type 1 (von recklinghausen’s disease)

A
  • Autosomal dominant
  • mutation on long arm of chromosome 17
  • Findings: café-au-lait spots, neural tumors lisch nodules (pigmente diris hamartomas), skeletal disorders (e.g., scoliosis), optic pathway gliomas
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Neurofibromatosis type 2

A
  • Autosomal dominant
  • affects NF2 gene on chromosome 22
  • leads to bilateral acousic schwannomas, juvenile cataracts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Tuberous sclerosis

A
  • Autosomal dominant
  • Incomplete penetrance with variable presentation
  • causes non-malignant tumors to grow in many vital organs
  • findings: facial lesions (adenoma sebaceum), hypopigmented “ash leaf spots” on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, renal angiomyolipomas, cardiac rhabdomyomas, incrased incidence of astrocytomas
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

von Hippel-Linday disease

A
  • Autosomal dominant
  • Associated with deletion of VHL gene (tumor suppressor) on chromosome 3 short arm
  • results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors
  • findings: hemangioblastomas of retina, cerebellum, medulla
  • majority of affected individuals develop multiple bilateral renal cell carcinomas and other tumors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Inheritance mode of Albinism

A

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Inheritance mode of ARPKD (formerly infantile polycistic kidney disease)

A

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Inheritance mode of Cystic fibrosis

A

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Inheritance mode of Glycogen storage diseases

A

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Inheritance mode of hemochromatosis

A

Autosomal recessive

40
Q

Inheritance mode of mucopolysaccharidoses (except Hunter’s)

A

Autosomal recessive

41
Q

Inheritance mode of phenylketonuria

A

Autosomal recessive

42
Q

Inheritance mode of sickle cell anemias

A

Autosomal recessive

43
Q

Inheritance mode of sphingolipidoses (except Fabry’s)

A

Autosomal recessive

44
Q

Inheritance mode of Thalassemias

A

Autosomal recessive

45
Q

Cystic fibrosis

A
  • autosomal recessive defect in CFTR gene on chromosome 7; commonly deletion of Phe 508
  • Mutation causes abnormal protein folding, l,eading to degradation of channel before reacing the cell surface
  • CFTR channel secretes Cl- in lungs and GI tract; this moves Na+ and water as well
  • CFTR channel reabsorbs Cl- from sweat
  • Defective Cl- channel leads to the secretion of abnormally thick mucus that plugs lungs, pancreas, and lever
  • Patients can get recurrent pulmonary infections (pseudomonas specias and S. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), nasal polyps, and meconium ileus (stools get stuck in ileus) in newborns
  • Infertility in males due to bilateral absence of vas deferens
  • Fat-soluble vitamin deficiencies
  • failure to thrive in infancy
  • Most common lethal genetic disease of white population
  • increased oncentration of Cl- in sweat test is diagnostic
  • treatment: N-acetylcysteine to loosen mucous plugs (it cleaves disulfide bonds within mucous glycoproteins)
46
Q

Inheritance mode of Bruton’s agammaglobulinemia

A

X-linked recessive

47
Q

Inheritance mode of Wiskott-Aldrich syndrome

A

X-linked recessive

48
Q

Inheritance mode of Fabry’s disease

A

X-linked recessive

49
Q

Inheritance mode of G6PD deficiency

A

X-linked recessive

50
Q

Inheritance mode of Ocular albinism

A

X-linked recessive

51
Q

Inheritance mode of Lesch-Nyhan syndrome

A

X-linked recessive

52
Q

Inheritance mode of Duchenne’s and Becker’s muscular dystrophy

A

X-linked recessive

53
Q

Inheritance mode of Hunter’s syndrome

A

X-linked recessive

54
Q

Inheritance mode of Hemophilia A and B

A

X-linked recessive

55
Q

Inheritance mode of Ornithine transcarbamoylase deficiency

A

X-linked recessive

56
Q

Duchenne’s muscular dystrophy

A
  • X-linked recessive disorder
  • frameshift mutation that leads to the deletion of dystrophin (DMD) gene (longest known human gene, so it has a higher rate of sponaneous mutation)
  • dystrophin helps anchor muscle fibers, primairly in skeletal and cardiac muscle; deletion leads to accelerated muscle breakdown
  • onset before 5 years of age
  • weakness begins in pelvic girdle muscles and progresses superiorly
  • pseudohypertrophy of calf muscles (fibrofatty replacement of muscle)
  • cardiac myopathy
  • Gowers’ maneuver (patient needs to use upper extremities to stand up)
  • diagnose by looking at increased CPK and muscle biopsy
57
Q

Becker’s muscular dystrophy

A
  • X-linked recessive mutation of dystrophin gene
  • less severe than Duchenne’s with onset in adolescence or early adulthood
  • diagnose by looking at increased CPK and muscle biopsy
58
Q

Fragile X syndrome

A
  • X-linked defect
  • trinucleotide repeate disorder (CGG)n
  • affects the methylation and expression of the FMR1 gene, which is important for neural development
  • leads to mental retardation, macroorchidism (enlarged testes), long face with large jaw, large everted ears, autism, mitral valve prolapse
  • second most common cause of genetic mental retardation (after Down syndrome)
59
Q

Mutation type of Huntington’s disease

A

Trinucleotide repeat expansion (GAG)n

60
Q

Mutation type of Myotonic dystrophy

A

Trinucleotide repeat expansion (GTG)n

61
Q

Mutation type of Friedreich’s ataxia

A

Trinucleotide repeat expansion (GAA)n

62
Q

Mutation type of Fragile X syndrome

A

Trinucleotide repeat expansion (CGG)n

63
Q

Characteristics of trinucleotide repeat expansion diseases

A

May show genetic anticipation: successive generations show increased disease severity and lower age of onset

64
Q

Down syndrome

A
  • Trisomy 21 {Drinking Age is 21)
  • frequency 1:700; Most common viable chromosomal disorder; most common cause of genetic mental retardation
  • findings: mental retardation, flat facies, prominent epicanthal folds, simian crease, gap between first 2 toes, duodenal atresia, congenital heart disease (ostium primum ASD)
  • associated with increased risk of ALL and alzheimer’s disease
  • 95% of cases due to meiotic nondisjunction; associated with advanced maternal age; 1:25 women > 45; 1:1500 women < 20
  • 4% of cases due to Robertsonian translocation
  • 1% of cases due to down mosaicism (no maternal association)
  • quad test: low alpha-fetoprotein, high beta-hCG, low estriol, high inhibin A
  • ultrasound in first trimester shows increased nuchal translucency
65
Q

Edwards’Syndrome

A
  • Trisomy 18 {Election age is 18}
  • frequency: 1:8000; second most common trisomy resulting in live birth (after Down syndrome)
  • Findings: severe mental retardation, rocker-bottom feet, micrognathia (small jaw), low-set ears, clenched hands, prominent occiput, congential heart disease
  • death usually occurs withn a year of brith
  • quad screen: low alpha-fetoprotein, low beta-hCG, low estriol, normal inhibin A
66
Q

Patau’s syndrome

A
  • Trisomy 13 {Puberty age is 13}
  • frequency: 1:15,000
  • findings: severe mental retardation, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly (hemispheres don’t divide in two), polydactyly, congenital heart disease
  • death usually occurs within one year of brith
  • first-trimester pregnancy screen: low free beta-hCG, low PAPP-A, high nuchal translucency
67
Q

Quad test

A

Test during second trimester of mother plasma levels of: alpha-fetoprotein, beta-hCG, estriol, inhibin A

68
Q

Robertsonian translocation

A
  • Commonly involves acrocentric chromosomes (those with centromeres near their ends): 13, 14, 15, 21, 22
  • Long arms of two chromosomes fuse at the cnetromere; the two short arms fuse as well, but they are lost
  • Balanced translocations do not cause abnormal phenotype, but unbalanced translocation can result in miscarriage, stillbirth, and chromosomal impalanced (trisomies)
69
Q

Cri-du-chat syndrome

A
  • Congenital microdeletion of short arm of chromosome 5: 46,XX/XY, 5p-
  • Findings: microcephaly, moderate to severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities (VSD)
70
Q

Williams syndrome

A
  • Congenital microdeletion oflong arm of chromosome 7 (contains elastin gene)
  • findings : “elfin” facies, intellectual disability, hypercalcemia (increased sensitivity to vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems
71
Q

22q11 deletion syndromes

A
  • microdeletion at 22q11
  • leads to aberrant development of 3rd and 4th branchial pouches
  • variable presentation including: cleft palate, abnormal facies, thymic aplasia leading to T-cell deficiency, cardiac defects, hypocalcemia (secondary to parathyroid aplasia)
  • DiGeorge syndrome: thymic, parathyroid, and cardiac defects
  • Velocardiofacial syndrome: palate, facial, and cardiac defects
72
Q

Fat-soluble vitamins

A
  • A, D, E, K
  • absorption is dependent on gut (ileum) and pancrease
  • toxicity is more common that for water-soluble vitamins because they accumulate in fat
  • malabsorption syndromes (steatorrhea), such as cystic fibrosis and sprue, or mineral oil intake can cause fat-soluble vitamin deficiencies
73
Q

Water-soluble vitamins

A
  • B1, B2, B3, B5, B6, B7, B9, B12, C
  • all wash out easily from body except B12 and folate (B9), which are stored in the liver
  • B-complex deficiencies often result in dermatitis, glossitis, and diarrhea
74
Q

Vitamin A

A

• Retinol {Retinol is vitamin A, so think retin-A (used topically for wrinkles and acne)}
• antioxidant
constituent of visual pigments (retinal)
essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucous-secreting cells)
• Prevents squamous metaplasia
• Used to treat measles and AML (subtype M3)
• Vitamin A can be of benefit in the treatment of measles infection in children
• Deficiency leads to: night blindness, dry skin
• Excess leads to: Arthralgias, fatigue, headaches, skin changes, sore throat, alopecia; teratogenic (cleft palate, cardiac abnormalities)
• found in liver and leafy vegetables

75
Q

Vitamin B1

A
  • Thiamine
  • In thiamine pyrophosphate (TPP),a cofactor for several enzymes in decarboxylation:
    • Pyruvate dehydrogenase (links glycolysis to TCA cycle)
    • alpha-ketoglutarate dehydrogenase (TCA cycle)
    • transketolase (HMP shunt)
    • Branched-chain amino acid dehydrogenase
    • {Alpha-ketoglutarate DH, TRansketolase, and Pyruvate DH are required for ATP synthesis}
  • Deficiency: Impaired glucose breakdown, leading to ATP depletion (worsened by glucose infusion); highly aerobic tissues(brain and heart) are afected first
  • Deficiency causes Wernicke-Korsakoff syndrome and beriberi; these are seen in malnutrition and alcoholism (secondary to malnutrition and malabsroptoin)
76
Q

Wernicke-Korsakoff

A
  • Thiamine (B1) deficiency {Ber1Ber1}
  • confusion, ophthalmoplegia, ataxia (classic triad)
  • confabulation, personality change, memorly loss (permanent)
  • damage to medial dorsan nucleus of thalamus, mammillary bodies
77
Q

Dry beriberi

A
  • Thiamine (B1) deficiency

* polyneuritis, symmetrical muscle wasting

78
Q

Wet beriberi

A
  • Thiamine (B1) deficiency

* high-output cardiac vailure (dilated cardiomyopathy), edema

79
Q

Vitamin B2

A
  • Riboflavin
  • cofactor in oxidation and reduction (component of FADH2, FMN) {FAD and FMN come from riboFlavin (B2 = 2 ATP)}
  • Deficiency leads to: cheilosis and corneal vascularization {the 2 C’s of B2}
80
Q

Vitamin B3

A
  • Niacin
  • constituent of NAD+, NADP+ (used in redox reactions) {NAD derived from Niacin (B3 = 3 ATP)}
  • derived from tryptophan; synthesis requires vitamin B6
  • Deficiency can cause glossitis; severe deficiency leads to pellagra (Diarrhea, dementia, dermaatitis) {the 3 D’s of B3: Diarrhea, dermatitis, dementia}
  • deficiency can be caused by:
    • Hartnup disease (decreased tryptophan absorpion)
    • malignant carcinoid syndrome (increased tryptophan metabolism)
    • INH/isoniazid (vitamin B6 depletion)
  • excess can cause facial flushing (due to pharmacologic doses for treatment of hyperlipidemia)
81
Q

Vitamin B5

A
  • Pantothenate {B5 is “pento”thenate
  • Essential component of CoA (cofactor for acyl transfers) and fatty acid synthase
  • Deficiency leads to dermatitis, enteritis, alopecia, adrenal insuficiency
82
Q

Vitamin B6

A
  • Pyridoxine
  • it is converted to pyridoxal phsphate, which is a cofactor used in:
    • transamination (e.g., ALT and AST)
    • Decarboxylation reactions
    • Glycogen phoshporylase
  • Important for the synthesis of: cystathionine, heme, niacin, histamine, and neurotransmitters (serotonin, epinephrine, norepinephrine, GABA)
  • deficiency leads to: convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias (due to impaired hemoglobin synthesis and iron excess)
  • deficiency inducible by INH/isoniazid and oral contraceptives
83
Q

Vitamin B7

A
  • Biotin
  • Cofactor for carboxylation enzymes (adding 1-carbon group):
    • Pyruvate carboxylase: pyruvate to oxaloacetate
    • ACetylCoA carboxylase: acetyl-CoA to malonyl-CoA
    • Propionyl-CoA carboxylase: propionyl-CoA to methylmalonyl-CoA
  • Deficiency is rare; leads to dermatitis, alopecia enteritis
  • deficiency caused by antibiotic use or excessive ingestion of raw eggs {Avidin in egg whites avidly burns biotin}
84
Q

Vitamin B9

A
  • Folic acid
  • converted to tetrahydrofolate (THF), a conezyme for 1-carbon transfer/methylation reaction
  • Important for the synthesis of nitrogenous bases in DNA and RNA
  • found in leafy green vegetables {folate from foliage}
  • small reserve pool stored primarily in liver
  • deficiency leads to macrocytic, megaloblastic anemia (no neurologic symptoms as opposed to B12 deficiency)
  • most common vitamin deficiency in the US; seen in alcoholism and pregnancy
  • deficiency can be caused by many drugs (phenytoin, sulfonamides, MTX, etc)
  • supplemental folic acide in early pregnancy reduces neural tube defects
85
Q

Vitamin B12

A

• Cobalamin
• Cofactor for homocysteine methyltransferase: methyl-THF and homocysteine come in, THF and methionine come out
• cofactor for methylmalonyl-CoA mutase: isomerizes methlymalonyl-CoA to succinnyl-CoA
• deficiency leads to: macrocytic, megaloblastic anemia, hypersegmented PMNs, neurologic symptoms (accumulation of methylmalonyl in myelin sheath)
• prolonged deficiency leads to irreversible nervous system damage
• found in animal products and it is only synthesized by microorganisms
• very large reserve pool (several years) in the liver
Deficiency is usually caused by malabsorption (sprue, enteritis, diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn’s)
• Use schilling test to detect the etiology of the deficiency (test for absorption of radiolabeled B12)

86
Q

S-adenosyl-methionine (SAM)

A
  • Sam transfers methyl units in anabolic pathways
  • ATP + Methionine = SMA
  • required for the conversion of norepinephrine to epinephrine
  • regeneration of methionine (and thus SAM) is dependent on vitamin B12 and folate
87
Q

Vitamin C

A
  • ascorbic acid
  • Antioxidant found in fruits and vegetables
  • necessari for hydroxylation of proline and lysine in collagen synthesis
  • necessary for dopamine beta-hydroxylase, which converts dopamine to NE
  • facilitates iron absorption by keeping it in the Fe++ reduced state
  • deficiency leads to scurvy (swollen gums, brusing, ,hemarthrosis, anemia, poor wound healing) due to collagen synthesis defect
  • escess leads to nausea, vomiting, diarrhea, fatigue, sleep problems, risk of increased iron toxicity in predisposed individuals (transfusion, hemochromatosis, etc.)
88
Q

Vitamin D

A
  • D2 = ergocalciferol (ingested from plants)
  • D3 = cholecalciferol (consumed in milk, formed in sun-exposed skin)
  • 25-OH D3 is the storage form
  • 1,25 (OH)2 D3 (calcitriol) is the active form
  • calcitriol increases intestinal and renal absorption of calcium and phosphate; it leads to increases in bone mineralization
  • Deficiency leads to rickets in children (bone pain and deformity), and osteomalacia in adults (bone pain and muscle weakness), hypocalcemic tetany
  • Breast milk has less vitamin D (supplement in dark-skinned patients)
  • Excess leads to: hypercalcemia, hypercalciuria, loss of appetite, stupor;
  • Excess seen in granulomatous diseases (increased activation of vitamin D by epithelioid macrophages): sarcoidosis, TB, hodgkin’s disease, non-hodgkin’s lymphoma
89
Q

Vitamin E

A
  • antioxidant that protects arythrocytes and membranes from free-radical damage {E is for Erythrocytes}
  • deficiency leads to increased fragility of erythrocytes (hemolytic anemia), muscle weakness, posterior column and spiocerebellar tract demyelination
90
Q

Vitamin K

A
  • catalyzes gamma-carboxylation of glutamic acid residues on proteins concerned with coagulation (V, VII, IX, X, protein C, protein S) {K is for Koagulation}
  • synthesized by intestinal flora
  • Warfarin inhibits Vitamin K Epoxide Reductase (VKOR), which is necessary for the recycling of vitamin K so it can serve as a cofactor
  • Deficiency can lead to neonatal hemorrhage (increased PT and PTT but normal bleeding time) because neonates have no intestinal flora
  • deficiency can occur after prolonged use of broad-sprectum antibiotics
  • Not found in breast milk; neonates are given vitamin K injection at birth to prevent hemorrhage
91
Q

Zinc

A
  • Essential for the activity of hundreds of enzymes
  • Important in the formation of zinc fingers (transcription factor motif)
  • Deficiency leads to: delayed wound healing, hypogonadism, decreased adult hair (axillary, facial, pubic), dysgeusia, anosmia
  • zinc deficiency may predispose to alcoholic cirrhosis
92
Q

Ethanol metabolism

A
  • Ethanol is converted to acetaldehyde by alcohol dehydrogenase; In the process NAD+ is converted to NADH; this occurs in the cytosol
  • Acetaldehyde is converted to Acetate by acetaldehyde dehydrogenase; in the process NAD+ is converted to NADH; this occurs in mitochondria
  • NAD+ is the limiting reagent
  • Alcohol dehydrogenase operates via zero-order kinetics
93
Q

Fomepizole

A
  • Inhibits alcohol dehydrogenase

* antidote for methanol or ethylene glycol poisoning

94
Q

Disulfiram (antabuse)

A

Inhibits acetaldehyde dehydrogenase, leading to acetaldehyde accumulation (contributes to hangover symptoms)

95
Q

Ethanol hypoglycemia

A
  1. Ethanol metabolism increases the NADH/NAD+ ratio in the liver
  2. The increased ratio diverts Pyruvate to lactate (converts NADH to NAD+); it also diverts oxaloacetate to malate (converts NADH to NAD+)
  3. These reactions inhibit gluconeogensis and stimulate fatty acid synthesis, which lead to hypoglycemia and hepatic fatty change (hepatocellular steatosis) seen in chronic alcoholics
    • Overproduction of lactate leads to acidosis
    • Depletion of oxaloacetate shuts down the TCA cycle, shunting acetyl-CoA into ketone body production
    • Breakdown of excess malate increases NADPH and thus fatty acid syntheis
96
Q

Kwashiorkor

A
  • Protein malnutrition resulting in:
  • skin lesions
  • edema
  • liver malfunctions (fatty change due to decreased apolipoprotein syntehsis)
  • anemia
  • clinical picture is small child with swollen belly
97
Q

Marasmus

A

Energy malnutrition resulting in
• tissue and muscle wasting
• loss of subcutaneous fat
• variable edema

FA13 Biochemistry (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions