Biochem Factoids Flashcards
1
Q
Type I collagen
A
Strong; skin, bone, dentin
2
Q
Type II
A
Slippery: cartilage, vitreous, nucleus pulposus
3
Q
Type III
A
Bloody; blood vessels, skin, uterus, fetal tissue, granulation tissue
4
Q
Type IV
A
Basement membrane
5
Q
What type of protein processing occurs in RER
A
N-linked oligosaccharide addition
6
Q
Nuclear localization signal
A
4-8 Aas of lysine, arginine, and protein (essential for proteins bound for nucleus such as histones)
7
Q
Golgi protein modification
A
Modifies the N-oligosaccharides on Asparagine
8
Q
Golgi protein addition
A
O-oligosaccharides are added to Serine and Threonine
9
Q
Golgi targeting to lysosome
A
Mannose-6-phosphate, defect results in I-cell disease; clouded cornas, coarse facial features, restricted joints, high plasma lysosomal levels.
10
Q
G1 to S phase
A
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
Q
G2 to M phase
A
Mediated by Cyclin A and Cyclin B
12
Q
Chediak-Higashi syndrome
A
Problem with microtubule assembly; Parital albinism, peripheral neuropathy, recurrent pyogenic infection
13
Q
Kartageners syndrome
A
immotile cilia due to dynein arm defect. Infertility, bronchiectasis, and recurrent sinusitus; Assoc with situe inversus (10% have transposition of great vessels)
14
Q
Preprocollagen
A
the newly synthesized alpha chain in the RER
15
Q
ER Collagen Processing
A
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
Q
Extracellular processing of procollagen
A
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
Q
Elastin
A
Rich in proline and glycine, nonhydroxylated (vs. collagen). Tropoelastin with fibrillin scaffold – Desmosin crosslinking of elastin accounts for its properties
18
Q
Red infarcts
A
In tissues with multiple blood supplies or in reperfusion after infarction. Commonly, lungs, liver, and Intestins
19
Q
Pale infarcts
A
In tissues with single blood supply like heart, kidney, spleen
20
Q
Amino acids modified by golgi apparatus
A
Asparagine, threonine, serine
21
Q
glycolysis rate limiting step
A
Phosphofructokinase-1 (PFK-1)
22
Q
Gluneogenesis rate limiting enzyme
A
Fructose-1,6-bisphosphatase
23
Q
TCA cycle rate limiting enzyme
A
isocitrate dehydrogenase
24
Q
Glycogen synthesis rate limiting enzyme
A
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)
