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Flashcards in Biochem Factoids Deck (144):
1

Type I collagen

Strong; skin, bone, dentin

2

Type II

Slippery: cartilage, vitreous, nucleus pulposus

3

Type III

Bloody; blood vessels, skin, uterus, fetal tissue, granulation tissue

4

Type IV

Basement membrane

5

What type of protein processing occurs in RER

N-linked oligosaccharide addition

6

Nuclear localization signal

4-8 Aas of lysine, arginine, and protein (essential for proteins bound for nucleus such as histones)

7

Golgi protein modification

Modifies the N-oligosaccharides on Asparagine

8

Golgi protein addition

O-oligosaccharides are added to Serine and Threonine

9

Golgi targeting to lysosome

Mannose-6-phosphate, defect results in I-cell disease; clouded cornas, coarse facial features, restricted joints, high plasma lysosomal levels.

10

G1 to S phase

Cyclin D binds and activates CDK4 which phosphorylates Rb to release it from E2F --> synthesis of S components. Cell officially enters S phase when CDK2 is activated by Cyclin E

11

G2 to M phase

Mediated by Cyclin A and Cyclin B

12

Chediak-Higashi syndrome

Problem with microtubule assembly; Parital albinism, peripheral neuropathy, recurrent pyogenic infection

13

Kartageners syndrome

immotile cilia due to dynein arm defect. Infertility, bronchiectasis, and recurrent sinusitus; Assoc with situe inversus (10% have transposition of great vessels)

14

Preprocollagen

the newly synthesized alpha chain in the RER

15

ER Collagen Processing

Hydroxylation (vit. C) of proline and lysine; glycosylation of hydroxyllysine residues and formation of procollagen via hydrogen and disulfide bonds (this is the triple helix of 3 alpha chains) procollagen = triple helix

16

Extracellular processing of procollagen

The procollagen is proteolytically cleaved of its terminal regions to an insoluble tropocollagen; the process is completed by cross-linknig it to other molecules by lysyl oxidase (copper dependent) to make collagen fibrils

17

Elastin

Rich in proline and glycine, nonhydroxylated (vs. collagen). Tropoelastin with fibrillin scaffold -- Desmosin crosslinking of elastin accounts for its properties

18

Red infarcts

In tissues with multiple blood supplies or in reperfusion after infarction. Commonly, lungs, liver, and Intestins

19

Pale infarcts

In tissues with single blood supply like heart, kidney, spleen

20

Amino acids modified by golgi apparatus

Asparagine, threonine, serine

21

glycolysis rate limiting step

Phosphofructokinase-1 (PFK-1)

22

Gluneogenesis rate limiting enzyme

Fructose-1,6-bisphosphatase

23

TCA cycle rate limiting enzyme

isocitrate dehydrogenase

24

Glycogen synthesis rate limiting enzyme

glyogen synthase

25

Glycogenolysis rate limiting enzyme

glycogen phosphorylase

26

HMP shunt rate limiting enzyme

G6PD

27

Rate limiting step of de novo pyrimidine synthesis

Carbamoyl phosphate synthetase -II

28

Rate limiting step in purine synthesis

Glutamine-PRPP amidotransferase

29

Urea cycle

Carbamoyl phosphate Synthetase I

30

FA synthesis rate limiting step

Acetyl-CoA carboxylase

31

FA oxidation rate limiting step

Carnitine acyltransferase I

32

Ketogenesis rate limiting step

HMG-CoA synthase

33

Cholesterol synthesis rate limiting step

HMG-CoA reductase

34

malate-astpartate shuttle produces

32 ATP per glucose

35

Glycerol 3 phosphate shuttle

30 ATP per glucose

36

Purine Ring composition

Aspartate, CO2, Glutamine (nitrogen), glycine

37

Pyrimidine ring composition

Glycine and carbamoyl phosphate

38

Enzyme blocked by 6-MP

PRPP synthase

39

Mycophenolate mophetil inhibits what enzyme

PRPP synthase

40

TATA

promoter 25 base pairs upstream

41

CAAT

70 to 80 base pairs upstream

42

Enhancers and repressors location

can be anywhere within the gene upstream or downsream

43

tRNA characteristics

75 to 90 nucleotides, cloverleaf, 3'-CCA- aminoacyl end, 5' guanosine terminal

44

tRNA charging

Aminoacyl-tRNA synthetase; scrutinizes aa before and after binds to tRNA (if accidentally mischarged it will place in wrong aa).

45

tRNA structure

T(psi)C arm- sequence of thymidine and pseudoridine (3' side); D-arm (5' end) has dihydrouracil and acetylcytosine; arms are responsible for clover structure

46

Post-translational modificaiton in the RER

N-oligosaccharide addition

47

Modification in Golgi

N-oligosaccharide on Asparagine; O-oligosaccharide on serine and threonine; Mannose-6-phosphate for lysosome targeting

48

I-cell disease

failure of addition of mannose-6-phosphate to lysosome proteins; coarse facial features, clouded corneas. Restricted joints, high lysosomal enzymes in plasma

49

Peroxisome

Degradation of long fatty acids and amino acids

50

Proteasome

degradation of proteins marked by ubiquitin

51

Aerobic metabolism of glucose produces…

32 ATP via malate aspartate shuttle (heart and liver); 30 ATP via glycerol-3-phosphate shuttle (muscle)

52

Hexokinase

ubiquitous, low Km (high affinity) but low Vmax (low capacity)

53

Glucokinase

Liver and beta cells of pancreas. Low affinity (high Km) but really high Vmax (high capacity)

54

Hunter's

Iduronate sulfatase deficiency; heparan sulfate and dermatan sulfate; XR; Mild hurler's with aggressive behavior and no corneal clouding

55

Hurler's

alpha-L-iduronidase deficiency; Heparan sulfate; AR; developmental delay, corneal clouding, gargoylism (flat face, depressed nasal bridge and bulging forehead), hepatosplenomegaly, airway obstruction

56

Krabbe's

galactocerebroside buildup from lack of beta-galactocerebrosidase; peripheral neuropathy, developmental delay, optic atrophy, globoid cells (macrophages engorged with multiple nuclei in parenchyma and around blood vessels)

57

Metachromatic leukodystrophy

lack of arylsulfatase-A; Cerebroside sulfate buildup; demyelination, dementia, ataxia. AR

58

Niemann-Pick Disease

sphingomyelinase deficiency buildup of sphingomyelin; nerodegeneration, ashkenazi, hepatosplenomegaly, cherry red macula, foam cells

59

Tay Sachs

hexoaminidase A deficiency; GM2 buildiup; NO HEPATOSPLENOMEGALY (vs. Neimann pick); Cherry red macula, nervous degeneration, developmental delay, onion skin lysosomes

60

mitochondrial inheritance diseases

Leber's hereditary optic neuropathy (acute loss of central vision); myoclonic epilepsy, mitochondrial encephalopathy. Ragged red fibers on microscopy. Often due to failure in oxidative phosphorylation. All offspring

61

codominance

2 alleles, equal dominance; ie ABO blood groups

62

variable expression

severity of the phenotype varies form one to another; ie NF or Tuberous sclerosis

63

Plieotroy

one gene has more than one effect on phenotype; ie PKU

64

Locus heterogeneity

Mutations at different loci can produce same phenotype; Ie. Marfan's, MEN 2B, Homocystinuria (all three of these produce similar Marfan body habitus)

65

Mosaicism

cells have different genetic makeup in body;

66

Imprinting

uniparental disomy or inactivation or deletion of genes on Chromosome 15; Phenotype differences depend on wether mutaiton comes form mother or fathe

67

Prader-Willi

Paternal allel should be active but is deleted; has normally inactivated maternal allel; mental retardation, hyperphagia, obesity, hypogonadism, hypotonia; one of few causes of childhood osteoperosis

68

Angelman's syndrome

Maternal allel is deleted, normally inactivated paternal allele; Mental retardation, seizures, ataxia, inappropriate laughter

69

Rasburicase

Analog of Urate Oxidase (not present in humans), can catalyze uric acid into allantoin to help prevent renal toxicity in the case of tumor lysis syndrome. Allopurinol can be given as well.

70

Denosumab

Monoclonal antibody against RANKL to prevent osteoclast activation.

71

amino acids involved in the urea cycle

Aspartate (donates an NH3 to Citruline), and Argenine (produces urea and ornithine)

72

Electron transport chain complexes

I: NADH, II: Succinate dehydrogenase (FADH2) and CoQ, III: CoQ to III to Cytochrome C to IV (reduction of O2) to V (phosphorylation of ADP)

73

Inhibitors of electron transport complexes

Oligomycin (Complex V); Rotenone, amytal(barbituate), antimycin A, MPP from MPTP, CO, H2S, and CN-

74

Oxidative phosphorylation uncouplers

Thermogenin found in brown fat, aspirin, 2,4-DNP found in wood preservatives

75

Acute Intermittent Porphyria

HMB synthase or Uroporphyrinogen I synthase; buildup of porphobilinogen; abdominal pain, red-wine urine upon standing, increased urinary ALA and PBG, neurologic manifestations; can be precipitated by drugs like barbital, griseofulvin, and phenytoin, and alcohol.

76

ALA synthase regulation

substrates are glycine and Succinyl-CoA; Inhibited by glucose and heme; promoted by EtOH, Barbituates, and hypoxia

77

Porphyria cutanea tarda

Uroporphyrinogen decarboxylase deficiency; buildup of uroporphyrinogen III; Photosensitivity, blisters

78

JAK2 activation mutations relate to these disorders

All chronic myeloproliferative disorders except for CML (bcr-abl); Essential thrombocytosis, polycythemia vera, and Primary myelofibrosis (splenomegaly that causes early satiety, hepatomegaly, anemia and bone marrow fibrosis)

79

Ruxolitinib

JAK2 inhibitor approed for treatment of primary myelofibrosis

80

substrates for transcarbamoyl phosphate synthetase II

Glutamine and CO2 and ATP (for Pyrimidine synthesis)

81

substrates for transcarbamoyl phosphate synthetase I

CO2 and ATP and NH4+ (for Urea cycle)

82

Orotic aciduria enzymes

Orotate phosphoribosyl transferase (converts Orotic acid to UMP) an Orotidine 5'-phosphate decarboxylase[will NOT have hyperammonemia symptoms]; Ornithine transcarbamoyl transferase (in urea cycle so will cause hyperammonemia)

83

Steps of collagen synthesis and cellular location

alpha preprocollagen chains of Gly-X-Y (RER); Hydroxylation or pro and lys (ER); Glycosylation of lysine (ER); Assembly of procollagen (triple helix via disulfide bond formation in C-terminal propeptide); Secretion via golgi of procollagen into ECM; N and C terminal propeptide cleavage by propeptidase into insoluble tropocollagen; collagen fibril is cross-linked by lysyl oxidase to make collagen fibril polymers (copper dependent enzyme)

84

The main allosteric activator of Carbamoyl phosphate synthetase I

N-acetylglutamate (the main regulator of the urea cycle)

85

Kozak sequence

Methioning AUG codon is positioned near Kozak sequence b/c Kozak sequence (GccRcc, R=adenine or guanine), it serves to initate translation by helping mRNA bind to ribosomes, when there is a mutation in this sequence in beta-heme it can result in beta-thalassemia

86

Translocation step in translation

Requires eEF2 and GTP

87

Peptide bond formation on ribosome

catalyzed by peptidyl transferase on eurkaryotic ribosomes

88

bisphosphoglycerate mutase

enzyme that forms 2,3-BPG from 1,3-BPG from glycolytic pathway to be used by erythrocytes

89

Main allosteric activator of the key first step of gluconeogensis

Pyruvate carboxylase is activated by excess acetyl-CoA signaling a well fed state

90

How is oxaloacetate shuttled out of mitochondria for gluconegenesis in cytoplasm

oxaloactetate to Malate by malate dehydrogenase then malate is reconverted to oxaloacetate in the cytoplasm where it undergoes conversion to PEP by PEPCK (Uses GTP)

91

Four main metabolites of pyruvate

Lactate (regeneration of NAD+), Acetyl-CoA (FA synthesis, cholesterol synthesis, TCA), Oxaloacetate (gluconeogenesis), Alanine (in muscle cells to carry NH3 away to liver)

92

Key regulators of PFK-1

F2,6BP; made from F6P by PFK-2, PFK-2 is activated in the fed state (dephosphorylated) and inactivated in the starving state (phosphorylated via glucagon increase of cAMP and PKA). F2,6BP is deactivated by FBPase-2 which is active in starve state (phosphorylation) and inactive in fed state (dephosphorylation).

93

Cofactors for Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and Branched-chain alpha-ketoacid dehydrogenase

Lipoic acid, Thiamine, CoA, FAD, NAD

94

Products of B6 conenzyme reactions

GABA from glutamate, dopamine from dopa, heme from ALA synthase and glycine, histamine from histidine, Niacin from tryptophan

95

alkaptonuria

deficiency in homogentisic acid oxidase (a metabolite of Tyrosine on its way to fumarate); Usually a benign disease; find dark brown pigment in connective tissue and SCLERA because when homogentisate binds to collagen it turns dark; urine turns black on prolonged exposure to air. Can present with debilitating arthralgias

96

Roles of NADPH

anabolic reactions such as cholesterol and FA synthesis, reduction of glutathione, and production of oxidative burst

97

Where are Urea's nitrogens from?

Ammonium that is used to form carbamoyl phosphate and transferred to citruline; And Aspartate which donates an amino group to citrulline to form arginosiccinate.

98

How does the nephron rid of ammonium

Glutamine carries ammonia from peripheral tissues to the kidney where it is hydrolyzed by glutaminase in the tubule to produce glutamate and free ammonium ion where it is excreted in urine.

99

Two enzymes B12 is essential for

homocystein methyltransferase (to make methionine from homocysteine, also invovles folate); Methylmalonyl-CoA Mutase (or isomerase) to make succinyl coA from methylmalonyl-CoA

100

differentiating Cori's disease from other glycogen storage diseases

there is normal lactate levels and biopsy shows accumulation of short outer dextrin-like structures in the cytosol of hepatocytes with absence of histopathological fatty infiltration of the liver. Debranching enzyme affects liver and muscle cells but mainly presents with hepatocyte manifestations

101

Major biochemical defect in beta-thalaseemia

mutations affect the transcription, processing and translation of mRNA; this leads to decreased beta chain production

102

tetrahydrobiopterin is involved in what reactions

Phenylalanine to Tyrosine, tyrosine to Dopa; Tryptophan to Serotonin

103

Ach is made from

choline and acetyl-CoA from cholineacetyltransferase

104

Elastin versus collagen

Elastin can be stretched and recoil back; it is composed primarily of non-polar Aas gly, ala, and val. Also contains pro and lys. Fibrillin is the foundation/support. Desmosine corsslinking accounts for properties allowing it to recoil after being stretched. In skin, blood vessels, lungs. Differs from collage: very few proline and lysine are hydroxylated, no triple helix, hydroxylation, glycosylation, and intercahing disulfide bridges at C-terminus do not occur in elastin as in collagen.

105

myc

transcription factors

106

Ras

G-protein

107

Pyruvate dehydrogenase deficiency

congenital or acquired (ie alcohol); neurologic defects; Tx: increase ketogenic Aas (Lysine and Leucine)

108

Essential AA

Met, Val, Arg, His; Ile, Phe, The, Trp; Leu, Lys

109

Purely ketogenic Aas

Lysine, Leucine

110

Glucogenic and Ketogenic Aas

Ile, Phenylalanine, Threonine, Tryptophan

111

Glucogenic Aas

Methionine, Valine, Arginine, Histidine

112

Two ways the brain buffers ammonia

First alpha-ketoglutarate can be combined with NH4+ to yield glutamate; Glutamate itself can be used as a buffer in the astrocyte for ammonium by combining to make glutamine. Glutamine can be reconverted back to glutamate by glutaminase in the neuron for use by the pre-synaptic neuron

113

Ras-MAP kinase

Ras is a G-protein that binds GTP/GDP and is part of tyrosine kinase cascade where the tyrosine kinase receptor autophosphorylates itself, MAP is eventually activated and enters the nucleus where it can interact with the DNA

114

Sorbitol is produced and metabolized by what enzymes

Glucose or galactose are converted to sorbitol by aldose reductase. Sorbitol is then converted to Fructose by sorbitol dehydrogenase. Tissues like schwann cells, kidneys, etc. do not contain sorbitol reductase and are at risk for osmotic damage

115

A differentiating feature between Tay-Sachs and Neimann-Pick's disease is

Neimann-Pick's disease presents with hepatosplenomegaly whereas Sachs has no hepatosplenomegaly

116

NADPH Oxidase

Deficient in Chronic Granulomatous Disease; O2 to O2 radical

117

Superoxide dismutase

Converts O2radical into H2O2; second step in respiratory burst

118

Myeloperoxidase

Combines H2O2 with Chloride to form hypochlorous acid; final step in oxidative burst

119

Asparaginase treatment of Lymphoneoplastic cells

asparaginase breaks down normal asparagine to urea and ornithine; this is a useful treatment because lymphoblastic cells can not synthesize own asparagine so you are removing their supply

120

Deamination of glutamate gives

alphaketoglutarate

121

Deamination of alanine gives

Pyruvate

122

Cori Cycle

uses alanine and glutamate from muscle and transfers nitrogen to the liver by converting alpha ketoglutarate to glutamate and pyruvate to alanine; these transamination reactions all require B6

123

Treatment for Hyperammonemia

Benzoate, Phenylbutyrate (both bind amino acid); limit protein intake; Lactulose acidifies the GI and traps NH4+ in the colon for excretion

124

Cystinuria

AR defect in tubular transporter for cysteine, ornithine, lysine, and arginine in PCT of kidneys; hexagonal crystals of cysteine staghorn calculi; Acetazolamide to alkalinize the urine

125

Enzymes involved and location of Ketogenesis

Occurs in the mitochondria from Fatty acids. Fas go through Beta-oxidation and the Acetyl-CoA units are used to synthesize HMG-CoA via HMG-CoA synthase (same as for cholesterol); HMG-CoA is converted to acetoacetate by HMG-CoA Lyase (while cholesterol synthesis would start with HMG-CoA reductase); Acetoacetate can make beta-hydroxybutyrate with reduction by NADH. From there it enters bloodstream

126

Glycogen Phosphorylase Kinase regulation

phosphorylated by PKA via glucagon or adrenergic activation a la cAMP. The phosphorylation is activated and goes on to phosphorylate glycogen phosphorylase which does its business. Calcium/calmodulin also will activate Glycogen phosphorylase kinase in muscle; Insulin through its receptor tyrosine kinase will activate protein phosphatase which dephosphorylates glycogen phosphorylase kinase and glycogen phosphorylase

127

Carnitine deficiency

Can not transport LCFAs into mitochondira results in toxic accumulation; Weakness, hypotonia, Hypoketotic, Hypoglycemia

128

Acyl-CoA dehydrogenase deficiency

hypoglycemic hypoketonemia; increase in dicarboxylic acids and decrease in glucose and ketones

129

Rate limiting step in FA oxidation

Carnitine acyetyl transferase (inhibited by malonyl-CoA)

130

FA synthesis regulation

Acetyl-CoA carboxylase (uses biotin) is rate limiting step; Forms malonyl-CoA from Acetyl-CoA; Citrate moves from mitochondria via citrate shuttle to cytosol

131

Protein and carbs versus fat as kcal energy source

1 g of protein and carbohydrates = 4 kcal; 1 g of fate = 9 kcal

132

Name steps of heme breakdown from RES to Excretion in feces

Heme to biliverdin -> bilirubin -> transported to liver bound to albumin -> conjugated by UDP glucuronyl transferase -> conjugated bilirubin -> excretion to feces -> urobilinogen -> reabsorption to liver for reuse, feces and urine for color.

133

Crigler Najar

Absence of UDP Glucuronyl transferase

134

Gilbert's

Low levels of UDP-Glucuronyl transferase

135

Rotor's and Dubin-Johnson syndrome

Defective secretion of direct bilirubin into feces

136

Apo E

Mediates remnant uptake; seen on chlyomicrons

137

Apo A-1

Activates LCAT (Lecithin-cholesterol acyltransferase) which catalyzes esterification of cholesterol; Found on HDL

138

Apo C-II

Lipoprotein Lipase cofactor - degrades TG circulating in chlyomicrons and VLDLs

139

Apo B-48

Mediates chlyomicron secretion from enterocytes; found on chlyomicrons; deficiency in this leads to abetalipoproteinemia

140

Apo B-100

Binds LDL receptor; Found on LDL

141

Type I dyslipidemia: Hyper-Chlyomicronemia

Deficiency in Apo C-II or LPL; Increased Chlyomicrons and TG, and cholesterol; Causes pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas (no increased atherosclerosis risk)

142

Type Iia - Familia hypercholesterolemia

AD, Decreased LDL receptors; cholesterol increase in blood; atherosclerosis, xanthomas and corneal acrus

143

Type IV - Hypertriglyceridemia

Hepatic overproduction of VLDL; VLDL is elevated and TGs

144

Abetalipoproteinemia

ApoB-48 or Apo-B100; AR; Accumulation of chlyomicrons within enterocytes; failure to thrive, steatorrhea, acanthcytosis of RBCs, ataxia, night blindness (due to Vit A and Vit E deficiencies)