Biochemistry Flashcards

Question

What is the mechanism of action of allopurinol?

Answer 1

it inhibits xanthine oxidase of the purine metabolism pathway

Answer 2

it inhibits xanthine oxidase of the purine metabolism pathway

Answer 3

- deficiency of ADA, a protein required for degradation of adenosine and deoxyadenosine - absence causes an increase in dATP, which is toxic to lymphocytes - a major cause of autosomal recessive SCID

Answer 4

those rich in A and T

Answer 5

prevent strands from re-annealing during DNA replication

Answer 6

they inhibit prokaryotic topoisomerase II (DNA gyrase) and topoisomerase IV

Answer 7

etoposides are selective for eukaryotic topoisomerase II whereas fluoroquinolones are selective for prokaryotic ones

Answer 8

inhibit eukaryotic topoisomerase II

Answer 9

inhibit eukaryotic topoisomerase II

Answer 10

synthesis is 5' to 3'

Answer 11

- III has 5' to 3' synthesis and 3' to 5' proofreading activity - I degrades RNA primers and replaces them with DNA

Answer 12

an RNA-dependent DNA polymerase that adds DNA to 3' ends of chromosomes to avoid loss of genetic material

Answer 13

a point mutation from a purine to pyrimidine or pyrimidine to purine

Answer 14

a point mutation from a purine to purine or pyrmidine to prymidine

Answer 15

one in which the new amino acid is similar in chemical structure to the previous

Answer 16

- low glucose leads to more AC activity and the resulting cAMP activates CAP, an inducer which binds DNA and activates the transcription complex - high lactose binds the repressor protein and prevents it from binding the operator instead, which would otherwise block the transcription complex from moving downstream

Answer 17

defect in nucleotide excision repair prevents repair of pyrimidine dimers formed by UV light

Answer 18

- nucleotide excision: repairs bulky, helix-distorting lesions during G1 - base excision repair: repairs altered bases (e.g. spontaneous/toxic deamination) throughout the cell cycle - mismatch repair: fixes mismatched pairs after DNA replication during G2

Answer 19

aka HNPCC, this is caused by a defect in mismatch repair

Answer 20

- endonuclease release the damaged oligonucleotides | - DNA polymerase and ligase fill and reseal the gap

Answer 21

- base-specific glycosylase removes the altered base and creates an AP site - AP-endonuclease cleaves the 5' end of the segment to be removed and lyase cleaves the 3' end - DNA polymerase-beta fills the gap and ligase seals it

Answer 22

- used to repair a double strand break - simply brings together and joins the ends of two DNA fragments without any requirement for homology and so some DNA may be lost

Answer 23

mRNA is read in the 5' to 3' direction and protein synthesis occurs from the N- to C-terminus

Answer 24

AUG (codes for methionine in eukaryotes and fMet in prokaryotes)

Answer 25

UGA, UAA, UAG

Answer 26

they often have a modified 3'OH, which prevents addition of the next nucleotide

Answer 27

a promoter sequence

Answer 28

a site upstream from the gene locus which is AT-rich and is where RNA polymerase II and other transcription factors bind DNA

Answer 29

a site on DNA where negative regulators (i.e. repressors) bind

Answer 30

- I makes rRNA - II makes mRNA - III makes 5S rRNA and tRNA

Answer 31

- a compound found in Amanita phalloides (i.e. death cap mushrooms) - causes severe hepatotoxicity because it inhibits RNA polymerase II

Answer 32

it inhibits RNA polymerase in prokaryotes

Answer 33

it inhibits RNA polymerase in both prokaryotes and eukaryotes

Answer 34

aka heterogeneous nuclear RNA, it is the initial transcript that is then modified to become mRNA

Answer 35

- it must acquire a 5' cap, undergo polyadenylation of the 3' end, and undergo splicing out of introns - these processes all occur in the nucleus

Answer 36

- aka cytoplasmic processing bodies, they are responsible for mRNA quality control as well as occasionally the storage of mRNAs for future translation - have exonuclease activity, decapping enzymes, and miRNAs

Answer 37

small nuclear ribonucleoproteins responsible for splicing of pre-mRNA

Answer 38

a lopped intermediate that is generated during the coursing of intron splicing

Answer 39

they are directed against spliceosomal snRNPs and are highly specific for SLE

Answer 40

- they are antibodies against sliceosomal snRNPs | - associated with mixed connective tissue disease

Answer 41

- small, noncoding RNA molecules that post-transcriptionally regulate protein expression - binding triggers degradation or inactivation of the target mRNA - they are often contained within introns and can have multiple mRNA targets

Answer 42

- the acceptor stem is a conserved CCA 3' terminus on all tRNA that is covalently bound to the matching amino acid - T-arm contains a sequence necessary for tRNA-ribosome binding - D-arm contains dihydrouridine residues necessary for tRNA recognition by the correct aminoacyl-tRNA synthetase

Answer 43

an ATP-dependent enzyme that charges tRNA with the matching amino acid

Answer 44

eukaryotes on an 80S complex and prokaryotes on a 70S

Answer 45

- ATP is required for charging tRNA | - GTP is required for binding and translocation

Answer 46

- A: binding site for charged tRNA - P: accommodates the growing peptide - E: holds empty tRNA as it exits

Answer 47

CDKs are constitutively expressed but inactive until they bind a phase-specific cyclin

Answer 48

- induces p21, which inhibits CDK - results in hypophosphorylated Rb, which is the active form - Rb binds and inactivates E2F - this inhibits the G1-S progression

Answer 49

the hypophosphorylated form

Answer 50

- those that remain in Go unless stimulated to enter G1 | - includes hepatocytes and lymphocytes

Answer 51

it is the site of synthesis of secretory proteins

Answer 52

RER in neurons, which synthesize peptide neurotransmitters for secretion

Answer 53

- site of steroid synthesis and detoxification of drugs and poisons - hepatocytes and steroid-hormone producing cells of the adrenal cortex and gonads

Answer 54

it is the distribution center for proteins and lipids from the ER to the vesicles and plasma membrane

Answer 55

this is added in the golgi and is added to proteins to be trafficked to lysosomes

Answer 56

a kind of sorting center for material from outside the cell or from the Golgi, which sends these items to lysosomes for destruction or back to the membrane/golgi for continued use

Answer 57

- an inherited lysosomal storage disorder - arises from a defect in N-acetylglucosaminyl-1-phosphotransferase - the defect causes a failure of the Golgi to phosphorylate mannose residues on glycoproteins, so proteins necessary for the functioning of lysosomes are secreted extracellularly rather than delivered to lysosomes - presents with coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes; usually fatal in childhood

Answer 58

- it is a cytosolic ribonucleoprotein that traffics proteins form the ribosome to the RER - without it, proteins accumulate in the cytosol

Answer 59

- COPI is responsible fo retrograde transport within the golgi and from the cis-Golgi to the RER - COPII is responsible for anterograde transport from the RER to the cis-Golgi - Clathrin is responsible fo transport from the trans-Golgi to lysosomes and from the plasma membrane to endosomes

Answer 60

a transport protein responsible for moving vesicles from the trans-Golgi to lysosomes and from the plasma membrane to endosomes

Answer 61

a membrane-enclosed organelle involved in catabolism of VLCFAs, branched-chain FAs, amino acids, and ethanol

Answer 62

it is a barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins

Answer 63

- microfilaments mediate muscle contraction and cytokinesis - intermediate filaments maintain cell structure - microtubules mediate movement and cell division

Answer 64

- vimentin: mesenchymal tissue - design: muscle - cytokeratin: epithelial cells - GFAP: neuroglia (astrocytes, Schwann cells, oligodendroglia) - neurofilaments: neurons

Answer 65

alpha- and beta-tubulin heterodimers polymerize to form a hollow cylindrical structure

Answer 66

- dynein is responsible for retrograde transport | - kinesin is responsible for anterograde transport

Answer 67

- the length has a 9+2 arraignment of microtubule doublets | - the base, called the basal body, consists of 9 microtubule triplets without a central microtubule

Answer 68

an ATPase called axonemal dynein links peripheral microtubule doublets and causes bending via differential sliding

Answer 69

- a dynein arm defect, which leaves cilia immotile - results in male and female infertility, increases the risk of ectopic pregnancy, causes bronchiectasis, recurrent sinusitis, and situs inversus

Answer 70

- 3 sodium go out of the cell upon pump phosphorylation using ATP - 2 potassium come into the cell upon dephosphorylation

Answer 71

- I: bone, skin, tendon, dentin, fascia, cornea, and late wound repair - II: cartilage, vitreous body, and nucleus pulposus - III: blood vessels, granulation tissue, skin, uterus, and fetal tissue - IV: basement membrane, basal lamina, lens

Answer 72

- translation of collagen alpha chains known as preprocollagen with the form of Gly-X-Y where X and Y usually represent proline or lysine - hydroxylation of specific proline and lysine residues in a reaction that requires vitamin C - glycosylation of hydroxylysine residues - formation of procollagen, a triple helix of 3 alpha chains, via hydrogen and disulfide bond formation - exocytosis of procollagen into the extracellular space - cleavage of disulfide-rich terminal regions of pro collagen to form insoluble tropocollagen - cross-linking and reinforcement of staggered tropocollagen molecules via covalent lysine-hydroxylysine bonds by copper-containing lysyl oxidase, forming fibrils

Answer 73

lack of vitamin C prevents the hydroxylation of collagen

Answer 74

- scurvy: lack of vitamin C necessary for hydroxylation of proline and lysine residues of preprocollagen - osteogenesis imperfecta: problems forming the triple helix (procollagen) - Ehlers-Danlos: problems cross-linking tropocollagen

Answer 75

it is required by copper-containing lysyl oxidase, which catalyzes cross-linkage of staggered, insoluble tropocollagen units to form fibrils

Answer 76

- faulty collagen synthesis due to problems with cross-linking of tropocollagen units - presents with hyper extensible skin, a tendency to bleed, and hyper mobile joints - may also be associated with joint dislocation, berry and aortic aneurysms, or organ rupture - three types: hypermobility, classical, and vascular

Answer 77

- hypermobility: aka joint instability type, this is most common - classical: presents with joint and skin symptoms and is caused by a mutation in type V collagen - vascular: presents with vascular and organ rupture due to a deficiency of type III collagen

Answer 78

- an X-linked recessive connective tissue disease - caused by a defect in ATP7A, a protein responsible for copper absorption and transport, which leads to diminished activity of lysyl oxidase, the enzyme that links tropocollagen units to form fibrils - presents with brittle, kinky hair, growth retardation, and hypotonia

Answer 79

a1-antitrypsin

Answer 80

nonhydroxylated proline, glycine, and lysine

Answer 81

a glycoprotein scaffold for tropoelastin

Answer 82

- a connective tissue disorder affecting skeleton, heart, and eyes - due to a FBN1 gene mutation on chromosome 15 leads to defective fibrillin, a glycoprotein scaffold for elastin - presents as a tall, lengthy individual with pectus excavatum, hypermobile joints, and long, tapering fingers and toes - complications include necrosis of the aorta leading to incompetence and dissection, floppy mitral valve, and subluxation of the lenses (typically upward and temporally)

Answer 83

a decrease in collagen and elastin production

Answer 84

- denaturation (95 Celsius) - annealing (55 Celsius) - elongation (72 Celsius)

Answer 85

SNoW DRoP - southern: looking for specific DNA sequences using a complementary DNA probe - northern: looking for specific RNA sequences using a complementary DNA probe - western: looking for protein using a labeled antibody - southwestern: looking for DNA-binding proteins (e.g. transcription factors) using labeled oligonucleotide probes

Answer 86

a northern blot

Answer 87

- thousands of nucleic acid sequences are arranged in grids on glass or silicon and DNA or RNA probes are applied, after which a scanner detects the relative amounts of complementary binding - useful in detecting SNPs and copy number variations

Answer 88

- antibodies in a well specific for the target are linked to an enzyme - a substrate is added and reacts with the enzyme, producing a detectable signal, which can be measured

Answer 89

use of a fluorescent DNA or RNA probe, which binds to a specific gene site of interest on chromosomes in vitro, to indentify translocations, duplications, or microdeletions

Answer 90

cDNA lacks introns because it is formed from mRNA using a reverse transcriptase

Answer 91

- mRNA is isolated and exposed to reverse transcriptase, which produces cDNA - that cDNA is inserted into bacterial plasmids containing antibiotic resistance genes - the plasmid is transformed into bacteria - those bacteria are grown on an antibiotic medium and those that survive are known have the cDNA

Answer 92

a method used in mice to inducible manipulate genes (KO or knock-in) at specific developmental points

Answer 93

both alleles contribute to the phenotype of the heterozygote as in blood groups

Answer 94

a genetic trait for which the phenotype varies among individuals of the same genotype

Answer 95

a genetic trait for which not all individuals with a mutant genotype show the mutant phenotype as in BRCA1 mutations

Answer 96

the idea that one gene contributes to multiple phenotypic effects

Answer 97

- one that exerts a dominant effect because the heterozygote produces a nonfunctional, altered protein that also prevents the normal gene product from functioning - mutation of a transcription factor in its allosteric site will allow it to continue to bind DNA and prevent the wild-type from binding DNA

Answer 98

the tendency for certain alleles at two linked loci to occur together more or less often than expected by chance

Answer 99

the presence of genetically distinct cell lines in the same individual

Answer 100

- somatic: mutation arises from mitotic errors after fertilization and propagates through multiple tissues - gonadal: the mutation is only in egg or sperm cells

Answer 101

the idea that mutations at different loci can produce a similar phenotype

Answer 102

the idea that different mutations in the same locus can produce the same phenotype

Answer 103

- the presence of both normal and mutated mitochondrial DNA | - results in variable expression in mitochondrial inherited disease

Answer 104

both are when an offspring receives two copies of a chromosome from one parent and none from the other - heterodisomy: the individual is heterozygous and this indicates a meiosis I error - isodisomy: the individual is homozygous and this indicates a meiosis II error

Answer 105

it could be a case of isodisomy in which one parent contributed two copies of a chromosome and the other contributed none

Answer 106

- a mutation affecting G-protein signaling - this mutation would be lethal if it occurred before fertilization but individuals with mosaicism can survive it - presents with unilateral cafe-au-lait spots, polyostotic fibrous dysplasia, precocious puberty, and multiple endocrine abnormalities

Answer 107

- no mutation - natural selection is absent - completely random mating - no net migration

Answer 108

the idea that at some loci, only one allele is active and other is inactivated by methylation

Answer 109

because when only one allele is active, a single mutation or deletion can lead to disease (e.g. Prader-Willi and Angelman syndrome)

Answer 110

- presents with hyperplasia, obesity, intellectual disability, hypogonadism, and hypotonia - maternal allele is universally imprinted - 25% of cases, though, are due to maternal uniparental disomy in which two maternal alleles are inherited but are then both imprinted

Answer 111

- presents with inappropriate laughter, seizures, ataxia, and severe intellectual disability - paternal allele is imprinted but in 5% of cases, two paternally imprinted genes are received and no maternal allele is received

Answer 112

there is no male-to-male transmission and it skips generations

Answer 113

mothers transmit to 50% of offspring and fathers transmit to all daughters but no sons

Answer 114

- transmitted only through the mother | - heteroplasmy gives rise to variable expression in the population and within a family

Answer 115

- a group of disorders secondary to failure in oxidative phosphorylation - muscle biopsy tends to show "ragged red fibers" - presents with myopathy, lactic acidosis, and CNS disease

Answer 116

they are the genes involved in ADPKD and are located on chromosome 16 and 4, respectively

Answer 117

- elevated LDL due to an autosomal dominant defect or absence of the LDL receptor - leads to severe atherosclerotic disease early in life, corneal arches, tendon xanthomas

Answer 118

SBLA (sarcoma, breast, leukemia, and adrenal) cancer syndrome

Answer 119

an autosomal dominant neurocutaneous disorder with variable expression that presents with multi-organ involvement, characterized by numerous benign hamartomas

Answer 120

it is a tumor suppressor gene located on chromosome 3

Answer 121

- an autosomal dominant neurocutaneous disorder with 100% penetrance and variable expression - due to a mutation of the NF1 gene on chromosome 17 - presents with cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytoma, and Lisch noduels

Answer 122

- an autosomal dominant neurocutaneous disorder - caused by a mutation of the NF2 gene on chromosome 22 - presents with bilateral acoustic Schwannomas, juvenile cataracts, meningiomas, and ependymomas

Answer 123

- an autosomal recessive condition caused by a mutation of the CFTR gene on chromosome 7 - CFTR is an ATP-gated Cl- channel that secretes Cl- into the lungs and Gi tract and reabsorbs chloride ions in the sweat glands - most common is a deletion of Phe508, which causes a misfiling of the protein, which is then retained in the RER and not transported to the cell membrane - as a result, there is a rise in intracellular chloride ions and a compensatory increase in sodium reabsorption, which increases water reabsorption; water reabsorption causes the lung and GI tract secretions to become very thick; change in sodium causes a more negative trans epithelial potential difference - an increase in chloride concentration in the sweat is diagnostic; can also bee seen as a contraction alkalosis and hypokalemia - newborn screening looks for an increase in immunoreactive trypsinogen - complications include recurrent pulmonary infections (S. aureus in early infarct, P. aeruginosa in adolescence); chronic bronchitis and bronchiectasis; pancreatic insufficiency with malabsorption, steatorrhea, and fat-solute vitamin deficiencies; biliary cirrhosis and liver disease; meconium ileum in newborns; infertility in men; and sub fertility in women - treatment involves chest physiotherapy, albuterol, aerosolized dornase alfa (a DNAse), hypertonic saline for mucus clearance, azithromycin for prophylaxis, and pancreatic enzyme replacement

Answer 124

CFTR encodes an ATP-gated Cl- channel that secretes Cl- into the lungs and GI tract and reabsorbs chloride in the sweat glands

Answer 125

- an autosomal dominant muscular dystrophy - caused by a CTG repeat expansion in the DMPK gene, coding for an abnormal myotonia protein kinase - presents with myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, and arrhythmia

Answer 126

- an X-linked dominant condition arising from a trinucleotide repeat of the FMR1 gene that leads to methylation and diminished expression - presents with post-pubertal macroorchidism, long face and large jaw, large everted ears, autism, and mitral valve prolapse - the second most common cause of genetic intellectual disability after Down's

Answer 127

- Huntington Disease: CAG - Myotonic Dystrophy: CTG - Friedreich Ataxia: GAA - Fragile X: CGG

Answer 128

- 95% of cases are due to meiotic nondisjunction, which increases in probability with advanced maternal age - 4% of cases due to unbalanced Robertsonian translocations between chromosome 14 and 21 - 1% from a post-fertilization mitotic error with mosaicism

Answer 129

- most often due to meiotic nondisjunction, which occurs with increasing probability given advanced maternal age - represents the most common viable chromosomal disorder and most common cause of genetic intellectual disability - presents with intellectual disability, flat facies, prominent epicentral folds, single palmar creases, and brushfield spots - can be diagnosed often in first-trimester with US showing increased nuchal translucency and hypoplastic nasal bone, low serum PAPP-A, and increased free B-hCG - findings in the second-trimester include low a-fetoprotein, increased B-hcG, low estriol, and increased inhibin A - associated with duodenal atresia, Hirschsprung disease, AV septal defects, early-onset Alzheimer's, and ALL or AML

Answer 130

- also known as trisomy 18 - presents with severe intellectual disability, rocker-bottom feet, micrognathia, low-set ears, clenched hands with overlapping fingers, and congenital heart disease - death is usually within 1 year of birth - in utero, PAPP-A and free B-hCG are usually low during the first trimester; second trimester shows low a-fetoprotein, low B-hCG, low estriol, and low or normal inhibin A

Answer 131

- Down: increased nuchal translucency, hypoplastic nasal bone, low serum PAPP-A, increased free B-hCG, low estriol, high inhibin A, and low a-fetoprotein - Edwards: low PAPP-A, low B-hCG, low a-fetoprotein, low B-hCG, low estriol, and low or normal inhibin A - Patau: low free B-hCG and low PAPP-A

Answer 132

- also known as trisomy 13 - in utero, free B-hCG and PAPP-A are both low - presents with severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly - death usually occurs in one year

Answer 133

- a chromosomal translocation in which the long arms of 2 afrocentric chromosomes (those with a centromere near their ends) fuse at the centromere - the short arms are generally lost leaving a one normal chromosome E, one normal chromosome F, and one fusion chromosome (instead of the original 4 normal chromosomes) - offspring can end up being monosomy, disomy, or trisomy depending on the gamete that is formed - usually involves 13, 14, 15, 21, or 22

Answer 134

- a congenital micro deletion of the short arm of chromosome 5 - presents with microcephaly, moderate-to-severe intellectual disability, high-pitched crying/mewing, epicentral folds, and cardiac abnormalities (VSD)

Answer 135

- a congenital micro deletion of the long arm of chromosome 7, which contains the elastin gene - presents with an "elfin" face, intellectual disability, hypercalcemia (increased sensitivity to vitD), well-developed verbal skills, extreme friendliness, and cardiovascular problems

Answer 136

A, D, E, and K

Answer 137

- found in liver and leafy vegetables - it is an antioxidant - constituent of visual pigements - essential for the normal differentiation of epithelial cells in specialized tissues and prevents squamous metaplasia - oral supplementation, in the form of isotretinoin, is used to treat severe cystic acne

Answer 138

- night blindness (aka nyctalopia) - dry, scaly skin (aka xerosis cutis) - corneal degeneration (keratomalacia) - bitot spots on conjunctiva - immunosuppression

Answer 139

- acute: nausea, vomiting, vertigo, and blurred vision - chronic: alopecia, dry skin, hepatotoxicity, enlargement of arthralgia, and pseudotumor cerebri - also a teratogen causing cleft palate and cardiac abnormalities

Answer 140

an oral vitamin A supplement used to treat severe cystic acne, but which requires a negative pregnancy and two forms of contraception prior to its use because of it's teratogenic effects (clef palate and cardiac problems)

Answer 141

- also known as thiamine, it is an important component of thiamine pyrophosphate, a cofactor for several dehydrogenase enzyme reactions - necessary for pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, transketolase of the HMP shunt, and branched-chain ketoacid dehydrogenase - deficiency often arises from malnutrition (known as Beri Beri) or alcoholism (known as Wernicke-Korsakoff syndrome) - as a result of the deficiency glucose breakdown is impaired and ATP depletion worsens with glucose infusion, particularly in highly aerobic tissues like brain/heart - diagnose with observation of an increase in RBC transketolase activity following B1 administration

Answer 142

- beriberi refers to a vitamin B1 deficiency resulting from malnutrition - dry presents with polyneuritis and symmetrical muscle wasting - wet presents with high-output cardiac failure, secondary to dilated cardiomyopathy, and edema

Answer 143

- also known as riboflavin, B2 is a component in FAD and FMN, used for redox reactions - presents with cheilosis (inflammation of lips, scaling, and fissures at the corners of the mouth) and corneal vascularization

Answer 144

- also known as niacin, B3 is a constituent of NAD and NADP | - derived from tryptophan, synthesis requires vitamins B2 and B6

Answer 145

dyslipidemia, specifically, it lowers VLDL and raises HDL

Answer 146

- B3 is necessary for formation of NAD and NADP and it is derived from tryptophan, using B2 and B6 - caused by Hartnup disease (neutral amino acid transporter defect limiting tryptophan availability), carcinoid syndrome (increased tryptophan metabolism), and isoniazid (lowers B6 availability) - presents with glossitis and symptoms of pellagra: diarrhea, dementia with hallucinations, dermatitis along the C3/C4 dermatome ("broad collar" rash) with hyperpigmentation of sun-exposed limbs

Answer 147

- an autosomal recessive deficiency of neutral amino acid transporters in the proximal renal tubular cells and on enterocytes - results in neutral aminoaciduria and poor absorption from the gut - without tryptophan, there is a deficiency of niacin, presenting with pellagra (red, rough rash following sun exposure), diarrhea, and cerebellar ataxia - can be treated with a high-protein diet and niacin supplementation

Answer 148

with facial flushing (induced by prostaglandins and avoided by taking aspirin with niacin), hyperglycemia, and hyperuricemia

Answer 149

- also known as pantothenic acid - functions as an essential component of CoA and fatty acid synthase - deficiency presents with dermatitis, enteritis, alopecia, and adrenal insufficiency

Answer 150

- also known as pyridoxine - converted to pyridoxal phosphate (PLP), a cofactor for transamination, decarboxylation reactions, and glycogen phosphorylase - functions in the conversion of homocysteine to cysteine and succinyl-CoA to heme - deficiency can be induced by isoniazid or oral contraceptives and results in convulsions, hyper-irritability, peripheral neuropathy, and sideroblastic anemia

Answer 151

- also known as biotin - serves as a cofactor for carboxylation enzymes, which add 1-carbon groups - deficiency is rare but can be caused by antibiotic use or excessive ingestion of raw egg whites - presents with dermatitis, alopecia, and enteritis

Answer 152

- also known as folate - found in leafy green vegetables and absorbed in the jejunum - converted to THF, a co-enzyme for 1-carbon transfer/methylation reactions and critical for synthesis of nitrogenous bases in DNA an dRNA - deficiency is the most common vitamin deficiency in the US; seen in alcoholism and pregnancy - presents with macrocytic, megaloblastic anemia, hyper-segmented PMNs, glossitis, and no neurosymptoms - labs will show increased homocysteine and normal methylmalonic acid

Answer 153

- also known as cobalamin - found in animal products, the liver stores a very large reserve - functions as a cofactor for methionine synthase (converts homocysteine to methionine) and methylmalonyl-CoA mutase (converts methylmalonyl-CoA into succinyl-CoA) - deficiency caused by lack of intrinsic factor, malabsorption, absence of terminal ileum, or insufficient intake (veganism) - presents with macrocytic, megaloblastic anemia, hyper-segmented PMNs, paresthesias and subacute combined degeneration of all tracts due to abnormal myelin - associated with increased levels of homocysteine and methylmalonic acid levels

Answer 154

- also known as ascorbic acid - functions as an anti-oxidant, facilitates iron absorption by reducing it to the ferrous state, necessary for hydroxylation of proline and lysine in collagen synthesis, necessary for DA B-hydroxylase which produces norepinephrine - deficiency is known as scurvy, presenting with swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular hemorrhages, and "corkscrew hair" - excess causes n/v/d, fatigue, and calcium oxalate nephrolithiasis; can increase risk for iron toxicity

Answer 155

- ergocalciferol is D2 ingested from plants - cholecalciferol is D3 consumed in milk and formed in sun-exposed skin - 25-OH D3 is the storage form - calcitriol is also known as 1,25-(OH2) D3 and is the active form of D3

Answer 156

- an antioxidant that protects RBCs and membranes from free radical damage - deficiency results in hemolytic anemia, acanthocytosis, muscle weakness, and posterior column and spinocerebellar tract demyelination; neuro symptoms of B12 deficiency without the megaloblastic anemia, hypersegmented PMNs, or increased serum methylmalonic acid

Answer 157

by intestinal flora

Answer 158

vitamins D (continued oral) and K (injection at birth)

Answer 159

delayed wound healing, hypogonadism, diminished adult hair, dyspepsia, anosmia, and acrodermatitis enteropathica

Answer 160

- kwashiorkor is protein malnutrition resulting gin skin lesions, edema, and liver malfunction (presents as a small child with swollen abdomen) - marasmus is a total caloric malnutrition resulting in emaciation/muscle wasting with or without edema

Answer 161

an enzyme that inhibits alcohol dehydrogenase and is an antidote for methanol or ethylene glycol poisoning

Answer 162

it inhibits acetaldehyde dehydrogenase increasing hangover symptoms, which is beneficial in the treatment of alcoholism

Answer 163

all lead to the formation of acetaldehyde - via alcohol dehydrogenase using NAD in the cytosol - via catalase using hydrogen peroxide in the peroxisome - via CYP2E1, generating ROS, in the microsome acetaldehyde is converted to acetate in the mitochondria

Answer 164

- disfavors TCA production of NADH so acetyl-CoA is diverted to ketogenesis and lipogenesis, causing ketoacidosis and hepatosteatosis - pyruvate is fermented to lactate causing a lactic acidosis - oxaloacetate is fermented to malate, preventing gluconeogenesis (because of the need for oxaloacetate) and causing a fasting hypoglycemia - dihydroxyacetone phosphate is converted to glycerol-3-phosphate, which combines with fatty acids to make triglycerides, contribute to hepatosteatosis

Answer 165

because ethanol metabolism increases the NADH/NAD ratio, inhibiting TCA production of NADH, so acetyl-CoA is diverted to lipogenesis instead

Answer 166

- mitochondria: B-oxidation, acetyl-CoA production, TCA cycle, oxidative phosphorylation, ketogenesis - cytoplasm: glycolysis, HMP shunt, and synthesis of steroids, proteins, fatty acids, cholesterol, and nucleotides - both: heme synthesis, urea cycle, and gluconeogensis

Answer 167

- kinase: catalyzes transfer of a phosphate group from a high-energy molecule - phosphorylase adds an inorganic phosphate onto a substrate without using ATP - phosphatase removes a phosphate group from a substrate

Answer 168

an enzyme that catalyzes a redox reaction

Answer 169

an enzyme that relocates a functional group within a molecules

Answer 170

- phosphofructokinase-1 - activated by AMP and F-2,6-BP - inhibited by ATP and citrate

Answer 171

- fructose-1,6-bisphosphatase | - inhibited by AMP and fructose-2,6-bisphosphate

Answer 172

isocitrate dehydrogenase

Answer 173

- glycogen synthase - activated by glucose-6-phosphate, insulin, and cortisol - inhibited by epinephrine and glucagon

Answer 174

- glycogen phosphorylase - activated by epinephrine, glucagon, and AMP - inhibited by glucose-6-phosphate, insulin, and ATP

Answer 175

- glucose-6-phosphate dehydrogenase - activated by NADP+ - inactivated by NADPH

Answer 176

- carbamoyl phosphate synthetase II - activated by ATP and PRPP - inactivated by UTP

Answer 177

- glutamine-PRPP amidotransferase | - inactivated by AMP, IMP, and GMP

Answer 178

- carbamoyl phosphate synthetase I | - activated by N-acetylglutamate

Answer 179

- acetyl-CoA carboxylase - activated by insulin and citrate - inactivated by glucagon and palmitoyl-CoA

Answer 180

- carnitine acyltransferase I | - inactivated by malonyl-CoA

Answer 181

HMG-CoA synthase

Answer 182

- HMG-CoA reductase - activated by insulin and thyroxine - inactivated by glucagon and cholesterol

Answer 183

because they are often key regulatory points

Answer 184

- 32 via the malate-aspartate shuttle in the heart and liver | - 30 via the glycerol-3-phosphate shuttle in muscle

Answer 185

- it causes glycolysis to produce zero net ATP because it inhibits lipoid acid, a cofactor required by pyruvate dehydrogenase - it presents with vomiting, rice-water stools, and garlic breath

Answer 186

- CoA carries an acyl group - lipoamide carries an acyl group - biotin carries a CO2 group - THF carries a 1 carbon unit - SAM carries methyl groups - TPP carries aldehydes

Answer 187

B3 and B2, respectively

Answer 188

- anabolic processes - respiratory burst - microsomal enzyme system - glutathione reductase

Answer 189

- glucokinase is expressed in the liver and by B-islet cells; it has a low affinity (high Km) and high capacity (high Vmax), is induced by insulin, and is not inhibited by glucose-6-phosphate - hexokinase is expressed by most tissues constitutively, has a higher affinity (low Km) and lower capacity (low Vmax), and is inhibited by glucose-6-phosphate - as a result glucokinase doesn't really turn on or function maximally until all other tissues are receiving adequate glucose

Answer 190

glucokinase

Answer 191

- hexokinase/glucokinase and PFK-1 both require ATP | - phosphoglycerate kinase (1,3-BPG --> 3-PG) and pyruvate kinase (PEP --> pyruvate) both produce ATP

Answer 192

- PFK-2 and FBPase-2 are the same, bifunctional enzyme (converts between F-6-P and F-2,6-BP) whose function is reversed by PKA - in the fasting state, glucagon triggers an increase in cAMP, which activates PKA, leading to more FBPase-2 activity and less PFK-2 activity; the balance tips toward greater F-6-P production and less F-2,6-BP production; without F-2,6-BP, PFK-1 isn't allosterically activated and less glycolysis occurs - in the fed state, insulin triggers a decrease in cAMP, which results in less PKA activity; this favors activation of PFK-2 and production of more F-2,6-BP, which allosterically activates PFK-1 and drives glycolysis forward

Answer 193

- it is a mitochondrial enzyme complex linking glycolysis and the TCA cycle - it catalyzes the conversion of pyruvate to acetyl-CoA with the production of one NADH and CO2 molecule - it is composed of three enzymes requiring five cofactors: thiamine pyrophosphate (B1), lipoic acid, CoA (B5), FAD (B2), and NAD (B3) - it is activated by a high NAD/NADH ratio, ADP, and calcium

Answer 194

TLC For Nancy - thiamine pyrophosphate (B1) - lipoic acid - CoA (B5) - FAD (B2) - NAD (B3)

Answer 195

- an X-linked metabolic disorder - the deficiency causes a buildup of pyruvate, which is shunted to lactate ( via LDH) and alanine (via ALT) - presents with neurologic defects, lactic acidosis, and an elevated serum alanine starting in infancy - treat by increasing intake of ketogenic nutrients (high fat, lysine, or leucine content)

Answer 196

lysine and leucine

Answer 197

a method for getting regenerating glucose from pyruvate by cycling pyruvate through the liver while also transporting amino groups from skeletal muscle to the liver for disposal - begins with ALT transferring an amino group from an amino acid to pyruvate, forming alanine - alanine is transported in the blood to the liver - there in the liver, alanine is deaminated and pyruvate is reformed - the amino group is put into the urea cycle and the pyruvate undergoes gluconeogenesis - the glucose is then returned to skeletal muscle via the blood

Answer 198

a cycle used so that skeletal muscle can produce lactate during anaerobic periods from glucose, transport that lactate to the liver where it is reformed into glucose, and that glucose is delivered back to muscle for another cycle - LDH converts pyruvate to lactate - the lactate is transported via the blood to the liver - in the liver it is converted back to pyruvate and then glucose - the glucose is returned to the muscle via the blood

Answer 199

- both begin with pyruvate and involve transport of those carbon units to the liver for gluconeogenesis, which provides more glucose for muscle under anaerobic conditions - however, because the Cahill cycle is tied to transport of ammonia group, which the liver must use ATP to dispose of, it is favored only when the body is in a state of catabolism or there is a general need to get ride of ammonia - they also differ in that the Cori cycle requires NADH to reduce pyruvate to lactate, which is a form of energy expenditure - additionally, the Cahill cycle requires an alanine aminotransferase to begin the cycle whereas the Cori cycle requires LDH

Answer 200

- addition of an amino group by ALT for the Cahill cycle - reduction by LDH to lactate for the Cori cycle - production of acetyl-CoA for the TCA cycle by pyruvate dehydrogenase - production of oxaloacetate by pyruvate carboxylase, using biotin, to replenish the TCA cycle or be used for gluconeogensis (pyruvate can't go directly back to PEP)

Answer 201

3 NADH, 1 FADH2, 2 CO2, and 1 GTP per acetyl-CoA (x2 per glucose), which equals 10 ATP per acetyl-CoA

Answer 202

- NADH enters the mitochondria via the malate-aspartate or glycerol-3-phosphate shuttle and each generates 2.5 ATP - FADH2 transfers electrons directly to complex II of the electron transport chain and each generates 1.5 ATP

Answer 203

- rotenone inhibits electron transfer within complex I - antimycin A inhibits electron transfer within complex III - cyanide and CO inhibit electron transfer in complex IV - oligomycin inhibits complex V (ATP synthase) and so a proton gradient builds and electron transport stops - aspirin increases membrane permeability, reducing the proton gradient and uncoupling ATP synthase - 2,4-dinitrophenol increases membrane permeability, reducing the proton gradient and uncoupling ATP synthase

Answer 204

it increases membrane permeability, reducing the proton gradient and uncoupling ATP synthase from it

Answer 205

a uncoupling agent that increases membrane permeability for protons and is used illicitly for weight loss

Answer 206

- both inhibit the ETC and ATP production - however, aspirin and 2,4-dinitrophenol are uncoupling agents, so while ATP production is inhibited, electrons continue to flow and heat is generated instead of energy - oligomycin directly inhibits ATP synthase, the proton gradient builds, and electrons stop flowing without the generation of heat

Answer 207

- pyruvate carboxylase (pyruvate to oxaloacetate) - PEP carbokinase (oxaloacetate to PEP) - F-1,6-BPase (F-1,6-BP to F-6-P) - G-6-Pase (G-6-P to glucose)

Answer 208

pyruvate carboxylase requires ATP and PEP carboxykinase requires GTP

Answer 209

because it lacks glucose-6-phosphatase

Answer 210

- odd-chain FAs yield 1 propionyl-CoA molecule during metabolism, which can enter the TCA cycle as succinyl-CoA and contribute to gluconeogenesis - even-chain FAs only yield acetyl-CoA and cannot contribute to gluconeogenesis

Answer 211

- ketogenic are those that can be degraded directly into acetyl-CoA, a precursor for ketone bodies but not glucose - glucogenic are those that can enter the TCA cycle at or after succinyl-CoA and be converted to oxaloacetate for gluconeogenesis

Answer 212

- the oxidative part yields NADPH for anabolic reactions and ribulose-5-phosphate - the non-oxidative part takes ribulose-5-phosphate and forms primarily ribose-5-phosphate for nucleotide synthesis (in addition to fructose-6-phosphate and glyceraldehyde-3-phosphate)

Answer 213

- an autosomal recessive defect in fructokinase, which normally converts fructose to fructose-1-phosphate for entry into glycolysis - benign and asymptomatic since fructose is not trapped in cells; only sign is fructose in the blood and urine

Answer 214

those of galactose metabolism have more severe clinical presentations

Answer 215

- an autosomal recessive defect in aldolase B, which converts fructose-1-phosphate into DHAP for entry into glycolysis - fructose-1-phosphate accumulates and depletes phosphate, which inhibits glycogenolysis and gluconeogenesis - presents with hypoglycemia, jaundice, cirrhosis, and vomiting following the consumption of fruit, juice, or honey - urine dipstick will be negative but reducing sugar (positive copper test) can be detected in urine (non-specific) - treat by reducing intake of fructose and sucrose

Answer 216

a test for glucose in urine

Answer 217

it is a nonspecific test for inborn errors of carbohydrate metabolism

Answer 218

- an autosomal recessive deficiency of galactokinase, the enzymes that converts galactose to galactose-1-phosphate - galactose is instead shunted to production of galactitol by aldose reductase, which accumulates in the eye - relatively mild presentation with symptoms first appearing when infants begin feeding: galactosemia, galactosuria, infantile cataracts - may present as a failure to track objects or to develop a social smile (due to vision change)

Answer 219

- an autosomal recessive deficiency of galactose-1-phosphate uridyltransferase, which normally converts galactose-1-P to glucose-1-P - galactitol builds up and phosphate is depleted - symptoms include failure to thrive, jaundice, hepatomegaly, infantile cataracts because galactitol accumulates in the eye, and intellectual disability - may lead to E. coli sepsis in neonates - treat by excluding galactose and lactose from diet

Answer 220

- sucrose: glucose + fructose | - lactose: glucose + galactose

Answer 221

classic galactosemia and fructose intolerance are due to enzyme deficiencies that prevent further metabolism of phosphorylated compounds and therefore there is depletion of phosphoate in these disorders

Answer 222

- an osmotically active alcohol of glucose formed by aldose reductase - traps glucose in cells and is normally converted to fructose by sorbitol dehydrogenase

Answer 223

- it is an osmotically active alcohol of glucose - in those with a deficiency of sorbitol dehydrogenase or in tissues such as Schwann cells, retinal cells, and kidney cells without sorbitol dehydrogenase, sorbitol causes osmotic damage - this is particularly true in diabetics with chronic hyperglycemia, which drives production of sorbitol in these tissues without a way of riding it

Answer 224

an enzyme that converts glucose to sorbitol and galactose to galactitol, two osmotically active substances that can cause damage in tissues without sorbitol or galactitol dehydrogenase

Answer 225

because they express aldose reductase which converts glucose to the alcohol sorbitol, which is osmotically active, but they lack sorbitol dehydrogenase, so the substance accumulates and mediates osmotic damage

Answer 226

- Schwann cells - retinal cells - renal cells

Answer 227

- an insufficiency of lactase, which functions on the brush border to digest lactose into glucose and galactose - can be primary with an age-dependent decline after childhood due to an absence of the lactase-persistent allele; can be secondary due to a loss of the brush border to gastroenteritis or autoimmune disease; congenital deficiency is rare - presents with bloating, cramps, flatulence, and osmotic diarrhea - stool will have low pH and breath shows excess hydrogen content with a lactose hydrogen breath test - treatment is avoidance of dairy products or a lactase pill at meal times

Answer 228

- glucogenic: methionine, valine, histidine - ketogenic: leucine and lysine - both: isoleucine, phenylalanine, threonine, and tryptophan

Answer 229

aspartic acid and glutamic acid; therefore, negatively charged at body pH

Answer 230

- arginine is most basic | - lysine and histidine are also basic

Answer 231

because it depletes a-ketoglutarate, thus inhibiting the TCA cycle

Answer 232

- symptoms include tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision - treat by reducing protein in diet, using lactulose to acidify GI tract and trap ammonia for excretion, using rifaximin to reduce colonic ammoniagenic bacteria, and give benzoate, phenyl acetate, or phenyl butyrate to bind ammonia and enhance excretion

Answer 233

- a deficiency in the enzyme that produces the required cofactor for carbamoyl phosphate synthetase I of the urea pathway - causes hyperammonemia - presenting in neonates as poorly regulated respiration and body temperature, poor feeding, developmental delay, and intellectual disability - treat by reducing dietary protein, lactulose to acidy GI tract and enhance excretion, giving rifaximin to reduce colonic ammoniagenic bacteria, and benzoate, phenyl acetate, or phenyl butyrate to bind ammonia and enhance excretion

Answer 234

- an X-linked recessive deficiency which interferes with the body's ability to eliminate ammonia - usually presents in the first few days of life with tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision - labs find elevated orotic acid in blood and urine (because excess carbamoyl phosphate is converted to orotic acid) and low BUN - the most common urea cycle disorder

Answer 235

- Phe to tyrosine - tyrosine to throxyine (used) and dopa - dopa to melanin (used) and DA - DA to NE to Epi

Answer 236

- converted to niacin for NAD/NADP | - converted to serotonin and melatonin

Answer 237

porphyrin and heme

Answer 238

GABA and glutathione

Answer 239

creatine, urea, and nitric oxide

Answer 240

- an autosomal recessive metabolic disorder arising from diminished phenylalanine hydroxylase activity or lack of the tetrahydrobiopterin cofactor - inability to convert phenylalanine to tyrosine and to synthesize the catecholamines derived from it - presents with intellectual disability, growth retardation, seizures, fair skin (less melanin from DOPA), eczema, and a musty body odor - screened for 2-3 post-birth because maternal enzyme makes child normal at birth - labs find excess of phenylketones (phenylacetate, phenyllactate, and phenylpyruvate) in urine - treat with a diet low in phenylalanine (avoid the sweetener aspartame) and high in tyrosine plus tetrahydrobiopterin supplementation

Answer 241

- a form of PKU arising form lack of proper dietary therapy during pregnancy (not a genetic defect) - presents with microcephaly, intellectual disability, growth retardation, and congenital heart defects at birth

Answer 242

- an autosomal recessive metabolic disorder caused by reduced branched-chain alpha-ketoacid dehydrogenase activity - this enzyme deficiency blocks degradation of branched amino acids (isoleucine, leucine, and valine) - presents with vomiting, poor feeding, urine which smells like maple syrup or burnt sugar, severe CNS defects or intellectual disability - will find elevated alpha-ketoacids of these branched amino acids in blood, especially of leucine - treat with a restriction of branched amino acids in diet and thiamine supplementation (cofactor for deficient enzyme)

Answer 243

mutation of tyrosinase, the enzyme that converts DOPA to melanin

Answer 244

- an autosomal recessive deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate - pigment-forming homogentisic acid accumulates in tissue, which presents as bluish-black connective tissue and sclerae as well as urine that turns black with prolonged exposure to air - may also cause debilitating arthralgia since homogentisate is toxic to cartilage

Answer 245

- a group of autosomal recessive conditions that all result in excess homocysteine - can be caused by a cystathionine synthase deficiency, decreased affinity of cystathionine synthase for pyridoxal phosphate, or a methionine synthase deficiency - presents with homocysteinuria, intellectual disability, osteoporosis, marfanoid habits, kyphosis, lens subluxation (down and inward), thrombosis, and atherosclerosis - treat cystathionine synthase deficiency with a diet low in methionine

Answer 246

- an autosomal recessive cause of homocystinuria due to a deficiency of the enzyme or poor affinity of the enzyme for it's necessary cofactor, pyridoxal phosphate (B6) - homocysteine will be converted to methionine instead of to cystathionine and then cysteine - presents with homocysteinuria, intellectual disability, osteoporosis, marfanoid habits, kyphosis, lens subluxation (down and inward), thrombosis, and atherosclerosis - treated with a diet low in methionine but high in cysteine, B12, and folate if due to enzyme deficiency - treated with B6 and cysteine supplementation if due to poor affinity for the cofactor

Answer 247

all are autosomal recessive: - cystathinoine synthase deficiency - poor affinity of cystathionine synthase for pyridoxal phosphate (B6), a necessary cofactor - methionine synthase deficiency

Answer 248

- can be converted to methionine by methionine synthase using the cofactor B12 - can be converted to cystathionine by cystathionine synthase, using serine and the cofactor B6, which is then converted to cysteine

Answer 249

- an autosomal recessive cause of homocystinuria due to a deficiency of the enzyme - homocysteine will be converted to cystathionine and then cysteine instead of to methionine - presents with homocysteinuria, intellectual disability, osteoporosis, marfanoid habits, kyphosis, lens subluxation (down and inward), thrombosis, and atherosclerosis - treat with methionine supplementation

Answer 250

- an autosomal recessive defect of the PCT and intestinal amino acid transporter, which prevents reabsorption of cysteine, ornithine, lysine, and arginine (COLA) - excess cystine in the urine can lead to recurrent precipitation of hexagonal cystine stones (2 cysteine connected by a disulfide bone form cystine) - the urinary cyanide-nitroprusside test is diagnostic - treat with urinary alkalization, chelating agents, and good hydration

Answer 251

- glucagon binds a receptor in the liver and activates AC, causing a rise in cAMP, which activates PKA - PKA activates glycogen phosphorylase kinase, which phosphorylates glycogen phosphorylase, the enzyme responsible for liberating glycogen for gluconeogenesis - similarly, epinephrine binds a/B receptors, causing an influx in calcium and activation of AC, respectively, which both activate glycogen phosphorylase and lead to activation of glycogen phosphorylase - insulin, on the other hand, activates a tyrosine kinase dimer receptor and phosphorylates glycogen synthase, favoring production of glycogen

Answer 252

- linkages consist of a-(1,4) bonds | - branches consist of a-(1,6) bonds

Answer 253

- glucose to glucose-6-P by glucokinase in hepatocytes - glucose-6-P to glucose-1-P - glucose-1-P to UDP-glucose by UDP-glucose pyrophosphorylase - UDP-glucose to glycogen by glycogen synthase - branches are formed by the branching enzyme

Answer 254

- a lysosomal enzyme, which degrades a small amount of glycogen - not the primary pathway for glycogen degradation

Answer 255

- glycogen phosphorylase liberates glucose-1-phosphate residues from branched glycogen until 4 glucose units remain - then 4-a-D-glucanotransferase (aka debranching enzyme) moves three molecules of glucose-1-P from the branch to the linkage - then a-1,6-glucosidase (aka deb ranching enzyme) cleaves off the last residue, freeing glucose

Answer 256

a term used to refer to the one to four residues remaining on a branch of glycogen after glycogen phosphorylase has shortened it as far as it can

Answer 257

Very Poor Carbohydrate Metabolism - Von Gierke disease - Pompe disease - Cori disease - McArdle disease

Answer 258

- also known as type I glycogen storage disease - arises from a deficiency of glucose-6-phosphatase, the final enzyme necessary for converting glycogen to glucose - interferes with both gluconeogenesis and glycogenolysis - presents with severe fasting hypoglycemia; an increase in glycogen within the liver; high blood lactate, triglycerides, and uric acid; and hepatomegaly - treat with frequent oral glucose and avoidance of fructose or galactose

Answer 259

- also known as type II glycogen storage disease - arises from a defect of lysosomal a-1,4-glucosidase and a-1,6-glucosidase (the final debranching enzyme) - presents with cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, and early death ("Pompe trashes the pump")

Answer 260

- also known as type III glycogen storage disease - due to a defect of a-1,6,glucosidase (debranching enzyme) - gluconeogenesis is intact so it's milder than Von Gierke and has normal lactate levels - instead, there is an accumulation of limit dextrin-like structures in the cytosol

Answer 261

- also known as type IV glycogen storage disease - due to a deficiency of skeletal muscle glycogen phosphorylase (aka myophosphorylase) - blood glucose levels are typically unaffected but there is an increase in glycogen within muscle that cannot be broken down - this leads to painful muscle cramps, myoglobinuria with strenuous exercise, and arrhythmia from electrolyte abnormalities - "second-wind" phenomenon is a classic finding and exercise tolerance rises after about 10 minutes since there is an increase in muscular blood flow

Answer 262

- an X-linked recessive lysosomal storage disease - deficiency of a-galactosidase A - ceramics trihexoside accumulates in lysosomes - an early triad of episodic peripheral neuropathy, angiokeratomas, and hypohidrosis - a later stage with progressive renal failure and cardiovascular disease

Answer 263

- an autosomal recessive lysosomal storage disorder - deficiency of glucocerebrosidase - glucocerebroside accumulates in lysosomes - presents with hepatosplenomegaly, pancytopenia, osteoporosis, and avascular necrosis of the femur - histology finds Gaucher cells, lipid-laden macrophages resembling crumpled tissue paper

Answer 264

- an autosomal recessive lysosomal storage disorder - deficiency of sphingomyelinase - accumulation of sphingomyelin - presents with neurodegeneration, hepatosplenomegaly, foam cells, and a cherry red spot on the macula

Answer 265

- an autosomal recessive lysosomal storage disease - caused by a deficiency of hexosaminidase A, which converts GM2 to GM3 - GM2 ganglioside accumulates in lysosomes - presents with progressive neurodegeneration, developmental delay, a "cherry red" spot on the macula, lysosomes with onion skin, and no hepatosplenomegaly

Answer 266

- an autosomal recessive lysosomal storage disease - caused by a deficiency of galactocerebrosidase, which converts galactocerebrosidase to ceramide - galactocerebroside and psychosine accumulate - presents with peripheral neuropathy, developmental delay, optic atrophy, and globoid cells

Answer 267

- an autosomal recessive lysosomal storage disease - deficiency of arylsulfatase A - accumulation of cerebroside sulfate - presents with central and peripheral demyelination with ataxia and dementia

Answer 268

- most are autosomal recessive | - Fabry disease and Hunter syndrome are the exceptions, which are X-linked recessive

Answer 269

- both are autosomal recessive lysosomal storage diseases - both present with progressive neurodegeneration and a cherry-red spot on the macula - but Niemann-Pick is due to a sphingomyelinase deficiency and presents with foam cells as well as hepatosplenomegaly - whereas Tay-Sachs presents with lysosomes with onion skin and no hepatosplenomegaly

Answer 270

- an autosomal recessive lysosomal storage disease - caused by a deficiency of a-L-iduronidase - heparan sulfate and dermatan sulfate accumulate in lysosomes - presents with developmental delay, gargoylism, airway obstruction, corneal clouding, and hepatosplenomegaly

Answer 271

- an X-linked recessive lysosomal storage disease - caused by a deficiency of iduronate sulfatase - heparan sulfate and dermatan sulfate accumulate in lysosomes - presentation is like a mild Hurler syndrome (developmental delay, gargoylism, airway obstruction, and hepatosplenomegaly) plus aggressive behavior and without corneal clouding

Answer 272

- both are lysosomal storage diseases that cause the accumulation of heparan sulfate and dermatan sulfate - Hurler is autosomal recessive while Hunter is X-linked recessive - Hunter has a milder presentation than Hurler and has the addition of aggressive behavior without corneal clouding

Answer 273

the liver, lactating mammary glands, and adipose tissue

Answer 274

- an inherited defect in the carnitine shuttle, which is required for degradation of fatty acids - specifically, it transports fatty acyl-CoA into the mitochondria for further processing - LCFAs accumulate in the cytosol and are toxic - presents with weakness, hypotonia, and hypoketotic hypoglycemia

Answer 275

- citrate from the mitochondria is transported into the cytosol via the citrate shuttle - acetyl-CoA is formed by ATP citrate lyase - this is converted to malonyl-CoA with the addition of CO2 (using biotin)

Answer 276

- fatty acids + CoA are combined to form fatty acyl-CoA - they are transported into the mitochondria via the carnitine shuttle in a reaction inhibited by malonyl-CoA (an intermediate in FA synthesis) - in the mitochondria it undergoes beta-oxidation and acetyl-CoA is formed - this can be converted to ketone bodies or enter the TCA cycle

Answer 277

- an autosomal recessvie disorder of fatty acid oxidation - the inability to break down fatty acids into acetyl-CoA leads to accumulation of 8- to 10-carbon fatty acyl carnitines in the blood and hypoketotic hypoglycemia - presents in infancy with vomiting, lethargy, seizures, coma, and liver dysfunction - minor illnesses in the setting of this disease can lead to sudden death - treat by avoiding fasting

Answer 278

- in the liver, fatty acids and amino acids are broken down into units of acetyl-CoA, which are converted to HMG-CoA - HMG-CoA can be converted to acetoacetate and then onto B-hydroxybutyrate, which are both ketone bodies - extrahepatic tissues converted B-hydroxyburtyrate back into acetoactate - this is then attached to CoA using the TCA cycle and formed back into acetyl-CoA - acetyl-CoA can enters the TCA cycle itself for energy production

Answer 279

- acetone - acetoacetate can be detected in urine - B-hydroxybutyrate

Answer 280

- in prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis - certain tissues can't process fatty acids and other more complex nutrients, so acetyl-CoA from free fatty acids is shunted toward the production of ketone bodies - this process is also necessary in alcoholics who have excess NADH, which shunts oxaloacetate to malate and also impairs gluconeogenesis

Answer 281

- acetone is a ketone body formed in these situations - it is formed from acetoacetate while in the blood - this is expired by the lungs and gives the breath a fruity smell

Answer 282

- protein: 4 calories - carbohydrate: 4 calories - fat: 9 calories - alcohol: 7 calories

Answer 283

deliver sufficienct glucose to the brain and RBCs while preserving protein for as long as possible

Answer 284

- between meals, most energy comes from hepatic glycogenolysis under the direction of glucagon and epinephrine and some comes from hepatic gluconeogenesis and release of FFAs by adipose - after 1-3 days of starvation, there is a greater reliance on FFAs since glycogen stores are depleted after 24 hours of starvation; hepatic gluconeogenesis increases using peripheral tissue lactate and alanine as well as adipose tissue glycerol and propionyl-CoA from odd-chain FFAs - after 3 days, adipose stores are the primary source of energy with ketone bodies being the main energy source for the brain - onece adipose is depleted, protein catabolism begins

Answer 285

just 24 hours

Answer 286

HMG-CoA catalyzes the rate limiting step, converting HMG-CoA to mevalonate, and is induced by insulin

Answer 287

they competitively inhibit HMG-CoA reductase to limit cholesterol synthesis

Answer 288

- pancreatic lipase is responsible for the degradation of dietary triglycerides in the small intestine - lipoprotein lipase can be found on vascular endothelial surfaces and is responsable for degradation of triglycerides circulating in chylomicrons and VLDLs - hepatic TG lipase is responsible for the degradation of triglycerides remaining in IDL (remnant of VLDL) - hormone-sensitive lipase: degradation of triglycerides stored in adipocytes

Answer 289

- LCAT catalyzes the esterification of plasma cholesterol, transforming nascent HDL into mature HDL - CETP mediates the transfer of cholesterol esters from HDL to other lipoprotein particles such as VLDL, IDL, and LDL

Answer 290

- mediates remnant uptake | - found in chylomicrons, chylomicron remnants, VLDL, IDL, and HDL (just not LDL)

Answer 291

- responsible for activating LCAT, which esterifies plasma cholesterol - found in chylomicrons and HDL

Answer 292

- serves as a cofactor for lipoprotein lipase, the enzyme found on vascular endothelial surfaces that degrades triglycerides circulating in chylomicrons and VLDLs - found in chylomicrons, VLDL, and HDL

Answer 293

- mediates chylomicron secretion | - found in chylomicrons and chylomicron remnants

Answer 294

- binds the LDL receptor | - found in VLDL, IDL, and LDL

Answer 295

- they are secreted by intestinal epithelial cells and deliver dietary triglycerides to peripheral tissues - they delivery cholesterol to the liver in the form of chylomicron remnants, which are mostly depleted of their triglycerides

Answer 296

they are secreted by the liver and deliver hepatic triglycerides to peripheral tissues

Answer 297

it is formed from the degradation of VLDL and is responsible for delivering the remaining triglycerides and cholesterol to the liver

Answer 298

- formed by hepatic lipase modification of IDL in the liver and peripheral tissues - delivers hepatic cholesterol to peripheral tissues - taken up by target cells via receptor-mediated endocytosis

Answer 299

- secreted from both the liver and intestine - they mediate reverse cholesterol transport from the periphery to the liver (scavenger) and act as a repository for apolipoproteins C and E, which are needed for chylomicron and VLDL metabolism - their synthesis is increased by alcohol

Answer 300

- an autosomal recessive familial dyslipidemia - caused by a lipoprotein lipase or apolipoprotein C-II deficiency - labs will find high chylomicrons, triglycerides, and cholesterol in the blood - presents with pancreatitis, hepatosplenomegaly, and eruptive or pruritic xanthomas - does not increase the risk for atherosclerosis

Answer 301

- an autosomal dominant familial dyslipidemia - caused by the absence or defective nature of LDL receptors - labs find high LDL and cholesterol (heterozygous have cholesterol near 300 while homozygotes have nearly 700 mg/dL) - presents with accelerated atherosclerosis (MI before age 20 in some cases), tendon xanthomas, and corneal arcus

Answer 302

- an autosomal dominant familial dyslipidemia - caused by hepatic overproduction of VLDL - labs find high VLDL and triglycerides - hypertriglyceridemia can cause an acute pancreatitis