Biochemistry Flashcards
1
Q
Williams syn
A
deletion of chrom #7 long arm (include elastin gene); 特征性elfin faces, extremely friendly, cardiovascular problems hypercalceima (sensitive to VD)
2
Q
ADA deficiency
A
adenosine deaminase deficiency: purine salvage pathway (AR) excessive ATP and dATP: feedback inhibit ribonucleotide reductase - prevent DNA synthesis - decrease lymphocyte count - SCID, 1st disease treated with gene therapy
2
Q
Acyl-CoA Dehydrogenase
A
convert Acyl-CoA to Acetyl-CoA (for TCA or ketone formation) in beta-oxidation of FA deficiency: d. ketones and glucose, i. dicarboxylic acids (二羧酸)
2
Q
Abetalipoproteinemia
A
AR, Hereditary defect in Microsomal Triglyceride Transfer Protein (MTP) causing inability to synthesize Lipoproteins due to deficiencies in ApoB-100 and ApoB-48 to pack stuff into VLDLs and inability to transport Chylomicrons out of cells First appears in first few months of life Presentation: Lipid Vitamin Deficiencies due to d. transport Failure to Thrive, Steatorrhea, Acanthocytosis(棘红细胞[增多]症) Ataxia, Night Blindness (VA), Fou Smelling Stools (dec lipid absorb) Hyporeflexia, d. Vibratory Sense (Vitamin E Deficiency) Diagnosis: Intestinal Biopsy shows Lipid Accumulation within Enterocytes due to inability to export absorbed lipid as Chylomicrons, VLDLs or LDLs d.Total Cholesterol d. Fat-Soluble Vitamins
3
Q
snRNP function
A
remove introns from mRNAs SLE: Ab against U1-snRNP
4
Q
PRPP
↑ ↓
A
5’-phosphoribosyl - 1’- pyrophosphate, key intermediate for de novo synthesis of purines and pyromidines. Increase in PRPP synthetase can cause uric acid (product of purine degradation), - gout
4
Q
EDS
A
Ehlers–Danlos syndrome, AR or AD (6 types) defect in TypeI, III, V collagen: cross-linking hypermobile joints, skin hyperelasticity joint dislocation, berry aneurysms, organ rupture
5
Q
ataxia telangiectasia
A
共济失调性毛细血管扩张症 ATM mutated DNA repair mechanism in ATM: can’t join the ends of 2 DNA fragments to repair ds-DNA breaks
7
Q
Autosomal trisomies Downs
A
1:700, most commom cause of genetic retardation Drinking age: 21 孕检（abei): 低高低高（↓a-fetoprotein; ↑beta-hCG; ↓ estriol; ↑ inhibin A
7
Q
Fomepizole
A
甲吡脞 Inhibit ADH(alcohol DH), an antidote for MeTH or ethylene glycol poisoning
8
Q
carboxylase
A
transfer CO2 groups with the help of biotin (e.g., pyruvate carboxylase)
9
Q
carnitine shuttle
A
FA metabolism: b-oxidation: Acyl-CoA transferred by carnitine from outer mito membrane (CAT I) to inner membrane (CAT II), and form acetyl-CoA - go into TCA, or form acetoacetate (1 of the 3 major ketone bodies) carnitine deficiency impairs ketone body formation， cause hypoketonic hypoglycemia
9
Q
cavernous hemangioma
A
海绵状血管瘤
10
Q
malate - aspartate cycle
A
苹果酸-天冬氨酸循环 generate 32 ATP/glucose (aerobic metabolism in heart and liver)
10
Q
elastin-associated diseases
A
protein in skin, lung, arteries, vocal cords, ligamenta flava; rich in Gly and Pro, non-hydroxylated forms fibrillin scaffolding (Marfan’s syn, AD) broken down by elastase, which is inhibited by alpla1-antitrypsin (- emphysema,肺气肿）
10
Q
Chediak-Higashi syn. (CHS) 契东综合症
A
AR; mutation in LYST gene (LYSosome Trafficking regulatory gene). the gene product is required for the microtubule-dependent sorting of endosomal proteins no polymerization > no intracellular movt of vesicles > no fusion of phagosome & lysosome > no phagolysosome form > granular defects leukocyte defects in chemotaxis, degranulation, killing signs: 1) pyogenic infection (化脓性感染）2）partial albinism; 3) peripheral neuropathy 先天性白细胞颗粒异常综合征, AR 家族有近亲婚配史为一种原因不明的全身性疾病。具有以下特点：①部分性皮眼白化病伴有眼球震颤与畏光；②常发生化脓性感染；③巨溶酶体颗粒 其白细胞内有大块异常颗粒，主要是一种巨大溶酶体，含有多种水解酶。这些异常颗粒主要结合在溶酶体酶上亦可结合在其他细胞上它们使吞噬细胞趋化性减弱杀菌功能缺陷，故患者容易感染
10
Q
cell cycle: which protein is synthesized predominantly in S? Rb, p53 act on which phase? mutation result in
A
which protein is synthesized predominantly in S: histone (S = DNA synthesis) Rb, p53 act on which phase: G1 - S transition mutation result in Li-Fraumeni syn
12
Q
cobalamin
A
钴胺素， Vit B12 co-factor for homocysteine methyltransferase and methylmalonyl-CoA mutase 缺乏引起：megaloblastic anemia, hypersegmented PMN(blood smear shows >6 segments in neutrophils, sign for缺VB12的巨细胞贫血）, neurological syptoms包括paresthesias, abnormal myelin-subacute degeneration（as opposed to B9-叶酸 deficiency) very large pool stored in liver; deficiency caused by malabsorption(sprue口炎性腹泻，enteritis, lack intrnisic factors, lack terminal ileum (Crohn’s disease) 诊断：多步骤的Schilling test
13
Q
collagen synthesis
A
6步： inside fibroblast: 1-4 steps 1). RER: synthesize preprocol: Gly-X-Y (X, Y = Pro, Lys) 2). ER: hydroxylation of Lys (need Vc - scurvy) 3). ER: glycosylation of hydroxyLys- pro-col, form triple helix of 3 pro-Col chains via hydrogen bonds and disulfide bonds - Osteogenesis imperfecta 4). exocytosis Step 5-6: outside of fibroblast: 5). proteolytic processing: remove disulfide bonds: pro- become tropocollagen, insoluable 6) cross-linking: covalent, by Cu+-containing lysyl oxidase) ; EDS
14
Q
ETC
A
complex I: NADH dehydrogenase (NADH - NAD, electron transferred along the ETC) complex II: succinate dehydrogenase complex III： cyto b/c1 complex IV: cytochrome oxidase complex V: ATP synthase
14
Q
Cori’s disease
A
type III GSD, AR debranching E (a-1,6-glucosidase) milder form of type I (von Gierke’s), fasting hypoglycemia, but blood lactate is normal (gluconeogenesis is intact)
15
Q
cystic fibrosis (CF)
A
AR: Phe deletion in CFTR gene: mutation in the Cl- channal, most common lethal genetic disease in white population. thick mucus in lungs (recurrent pulmonary infection), chronic bronchitis, pancreatic insufficiency (malabsorption, steatorrhea脂溢性） 诊断：increase Cl- in sweat [note: if child with nasal polyps, which usually seen in adults: order a sweat test to R/O CF] 治疗：N-acetylcysteine to break up disulfide bonds in mucus glycoprotein, so loosen mucus plugs
16
Q
cystine
A
胱氨酸(made of 2 cysteine connected by disulfade bond)； cysteine: 半胱氨酸； homocysteine: 高胱氨酸
17
Q
Wernicke’s encephalopathy –Korsakoff syndrome
A
缺VB1 WE三联征：confusion, opthalmoplegia (paralysis (-plegia) of one or more extraocular muscles which are responsible for eye movements导致double vision), ataxia Korsakoff syndrome: acute onset of severe memory impairment
18
Vitamines: water- or fat- solubale?
fat soluble:ＫＥＡＤ （fat kid = kead) 能在脂肪中聚集，因此毒性比水溶性的大 water soluble: B1, 2,3, 5, 6, 7, 9, 12, C
20
Edward syn 爱德华病-国王的演讲
T18: 智障，rocker-bottom feet，头小下巴小，small jaw, low-set ears（国王口吃，因为听不见）；death within the 1st year; 2nd common live birth after Down's 明显心血管（先心病）和头部发育畸形 婴儿特征的手部：Clenched hand and overlapping fingers: index finger overlaps third finger and fifth finger overlaps fourth finger, characteristically seen in Trisomy 18. 孕检（abei): 低低低常（↓a-fetoprotein; beta-hCG; ↓ estriol; 正常 inhibin A
21
eu vs prokaryote ribosomal units
eu: (Even) 40S + 60 S = 80 S prOka(Odd): 30S + 50 S = 70S tRNA A-ctivation (charging): use ATP translocation use: GTP (going places)
21
ethanol hypoglycemia机制
1. increase NADH/NAD+ ratio in liver, cause pyruvate - lactate, OAA - malate - inhibit gluconeogenesis and TCA cycle 2. overproduce lactate - acidosis 3. depletion of OAA - shut down TCA, shunt acetyl-CoA to ketone production 4. break down excess malate increase NADPH - FAA synthesis 结果：低血糖，酸中毒，脂肪肝
22
Fabry's disease: 无法不理手脚的麻木
XR; deficient E.: a-galacosidase A: accumulation of ceramide trihexoside； findings: peripheral neuropathy of hands/feet, angiokeramotas (血管角质瘤）；cardiovascular/renal disease treatment: E. replacement (口服a-galactosidase A)
23
Vit E
antioxidant: protects erythocytes and membranes from free radical damage (E for erythrocytes); deficiency: hemolytic anemia; muscle weakness
23
folic acid
VB9, found in leafy green veggies, 储存在肝脏 converted to THF(tetrahydrofolate), important for the synthesis of nitrogenous bases in DＮＡ／ＲＮＡ(联想purine/pyramidine de novo syn;治疗：补thymine) ＵＳ最常见的vitamine deficiency; seen in alcoholism and pregnancy 症状：megaloblastic anemia, no neurological syptoms （as opposed to B12 deficiency); cause neural tube defects in pregnancy 3 drugs to induced deficiency：phenytoin(抗癫痫）， sulfonamides, MTX
25
Fragile x syndrome 脆弱的X染色体- 刘备（此人动不动就哭，脆弱综合征; 女里女气：x-chromosome problem）
Trinulceotide repeat expansion disease之一 X-Girlfriend: (CGG)n 刘备：大耳贼 巨大睾丸，长脸，大下巴，耳朵 智障 自闭。除downs 之外第二普遍的遗传智障（想想刘禅）
26
essential AA
AAs that need to be supplied from diet: 1) glucogenic: His, Met, Val (His met values) 2) ketogenic: Leu, Lys 3) glucogenic/ketogenic: He, Phe, Thr, Trp (HPTT)
27
free ribosome功能
synthesize cytosolic and organellar proteins
28
G6PDH deficiency
glucose-6-phosphate dehydrogenase deficiency: most common enzyme deficiency in human, X-linked recessive; more prevalent in Mediterraneans and blacks, increased resistance to malaria; through HMP shunt, G6PDH keeps the level of NAPDH (which keeps glutathione reduced to detoxify free radicals and peroxides). Decreased NADPH in RBCs leads to hemolytic anemia (excerabated by fava beans, infections) intrinsic defect, primarily intravascular hemolysis [can be induced by oxidative stress such as infection, and Fava beans] Heinz body: oxidized hemoglobin precipitated in RBC bite cells: splenic macrophages to remove Heinz bodies 诊断：active hemolysis screen with Heinz body prep
29
Gaucher's disease (戈谢病）
AR; deficiency in glucocerebrosidase (=G; 葡萄糖脑苷脂酶） - accumulation of glucocerebroside (葡萄糖脑苷脂）；most common LSD findings: hepatosplenogemaly (临床诊断中最常见的finding就是脾肿大, infiltrative diseases of macrophage in red pulp, lysosomal storage diease）； necrosis of femur; 骨髓检查见有典型戈谢细胞 (Gaucher cell: macrophages that look like crumpled tissue paper); 中枢神经系统症状
29
cardiac glycosides机制
digoxin, digitoxin directly inhibit Na+- K+ ATPase - indirectly inhibit Na+/Ca2+ exchange - increase [Ca2+]i - increase cardiac contractility
30
RER
site for : 1) secretory proteins 2) N-linked oligosaccharide (added to many proteins) cells rich in RER: goblet cells in intestine (mucus), B-cells (Ab) 特殊的RER: Nissl body (in neurons), make E. and neurotransmiters, e.g. ChAT
30
Gibbs free energy change (⊿G0) positive means? negative means?
Gibbs free energy change (⊿G0) positive: favor the formation of the substrates negative means: favor the formation of products 不可能为零（= - RT InKeq)
31
metabolism sites
mito: FAA oxidation (beta-oxidation),oxidation phosphorylation; TCA cycle, acetyl-CoA production cytoplasm: glycolysis; synthesis of FAA, steriod (SER), protein (RER), cholesterol; HMP shunt both: HUGs take two (heme synthesis, urea cycle, gluconeogenesis)
32
xeroderma pigmentosum
着色性干皮病， dna修复酶缺乏病
32
Hartnup disease
autosomal recessive, defect neutral aa transporter on renal and intestinal epithelial cells; Trp （neural aromatic aa) excretion in urine and decrease absorption from the gut; cause pellagra (糙皮病： Trp是形成niacin的前体； 也can be caused by chronic lack of niacin (vitamin B3) in the diet. It can be caused by decreased intake of niacin or tryptophan, and possibly by excessive intake of leucine) signs: ataxia, erythmatous skin lesion (红斑）， loose stool
32
Gower's sign
Duchenne's dystrophy特征，weakness of lower extremities
32
GSD: glycogen storage diseases
12 types: Very Poor Carbohydrate Metabolism, all AR type I: von Gierke's type II: Pompe's 庞培 type III: Cori's type V: McArdle's
34
hexokinase vs. glucokinase
hexokinse: expressed in all tissues expect liver and pancreas beta-cells; high affinity (low Km) and low capacity (low Vmax); uninduced by insulin; feedback inhibited by glucose-6-P glucokinase: in liver and pancreas beta-cell; low affinity (high Km), high capacity (high Vmax)。 it's the glucose sensor in pancreatic beta-cells: mutation caused d. insulin - hyperglycemia
36
Vit K
coagulation factors II, VII, IX and X, and anticoagulatant proteins C and S conditions predisposing to VitK deficiency: 1) fat malabsorption (bile duct occlusion) 2) prolonged use of broad spectrum antibiotics (kill bacteria in intestine for VK supplement) 3) breast-fed newborns (breast milk has no VK) manifestation in adults: poor nutrition, occult blood in stool, prolonged PT (prothrombin time), normal liver function
38
VC
Vc 4大功能：1）C stands for "collagen" (Vc is a cofactor for Pro and Lys hydroxylases 羟化酶 in collagen synthesis) 2）antioxidant 3）facilitate iron absorption by keep iron in Fe2+ in the reduced form 4) necessary for dopamine hydroxylase to convert dopamine to NE
39
glycolysis 糖酵解
happens in cytoplasm; convert 1 glucose into 2 pyruvate and release moderate energy aerobic: pyruvate goes into TCA Cycle + acetyl-CoA - FA synthesis; in RBC and exersicing skeletal muscle: pyruvate changes to lactate (NADH - NAD)
40
HNPCC / Lynch syn
heretidary non-polyposis colon cancer 遗传性非息肉性结肠直肠癌 mutation in DNA mismatch repair (unlike sporadic colon cancer, which involve mutations of proto-oncogenes or anti-oncogenes) adenoma ⇒ carcinoma sequence: APC ⟹ K-ras, p53,
41
homocysteinuria
高胱氨酸尿症 i. homocysteine in urine, mental retardation, osteoporosis, kyphosis, lens subluxation; atherosclerosis (stroke, MI) 3 forms (all AR): cysteine becomes essential and needs from diet 1) d. CTS (cystathionine synthase, 胱硫醚合成酶）treat: d. Met, i. Cys, B12 and folic acid from diet 2) d. affinity of CTS for pyridoxal phosphate (treat: d. VB6 in diet) 3) HCMT deficiency (homocysteine methyl-transferase), require VB12
42
riboflavin
核黄素， Vit B2, FAD, FMN cofactor in oxidation and reductation (eg, FADH2) B2 = 2 ATP (FAD. FMN) The 2 Cs of B2: cheilosis (唇干裂）， corneal vascularization
43
Hunter's syn
LSD/粘多糖storage disease: iduronate sulfatase (艾杜糖醛酸硫酸酯酶) - i. heparan sulfate, dermatan sulfate; XR milder version of Hunler's syn, aggressive behavior (because they are hunters), but no corneal clouding (hunters can see!)
44
hyperammonemia
acquired (liver disease) or hereditary (urea cycle E deficiency) excess NH4+ to deplete a-KG (shut down TCA) 表现：asterixis, blurring of vision, slurring of speech, vomit, cerebral edema, somnolence(嗜睡） Treat: limit protein in diet; Benzote, phenylbutyrate to bind aa for excretion; 3) lactulose to acidify GI and trap NH4+ for excretion
44
Hurler's syn
lysosomal/ mucopolysaccharidose storage disease, type I, AR 【Hunter's is XR!] a-L-iduronidase (艾杜糖苷酸酶) deficiency, i. heparan sulfate, i. dermatan sulfate (硫酸皮肤素） Symptoms appear during childhood and early death can occur due to organ damage（渐进性痴呆，10岁左右死亡） 症状：developmental delay, gargoylism（脂肪软骨营养不良）, airway obstruction, corneal clouding, hepatosplenomegaly [ 与 Hunter's鉴别：后者没有corneal clouding, 因为hunters can see!】
45
I cell disease
inclusion cell disease; fail to add mannose-6-p to lysosome E; so 溶酶体酶are secreted out of the cells instead of trafficking to lysosome; primary lysosome does NOT contain the E. Undigested substrates accumulate inside the cell as large inclusions in the cytosol inherited lysosome storage disorder: fatal in childhood signs: coarse facial features, cloud cornea, restricted joint movement; high plasma levels of lysosomal E
46
INH
isoniazid, 一线抗结核药
47
ketogenic nutrition
treat deficiency in alpha-ketoglutarate DH or pyruvate DH （这两个酶用的辅酶都一样，底物和反应也类似: increase lysine and leucine (Lysine and Leucine: the onLy pureLy ketogenic amino acid)
48
ketone bodies
酮体（Ketone bodies）是在机体饥饿、禁食或某些病理状态（如糖尿病）下产生的一类化合物，它包括丙酮、乙酰乙酸和β-羟丁酸三种化合物。 机体在上述状态时，脂肪动员加强，大量的脂肪酸被肝细胞吸收和氧化；而同时为了维持血糖浓度的稳定，体内的糖异生也得到激活。糖异生的原料草酰乙酸OAA被大量消耗，影响到草酰乙酸所参与的另一代谢途径TCA，大量中间物乙酰CoA得不到消耗、出现堆积，并因此生成酮体。 酮体在产生以后可以离开肝细胞进入血液，经由血液循环到达肝外组织，其中丙酮经肺被呼出体外，而另两种酮体则可重新转变为乙酰CoA进入三羧酸循环。这过程在肝外细胞发生（肝细胞内缺乏相关的酶. ketone bodies是机体在饥饿、禁食等状态下，为脑、骨骼肌和心肌提供的一种替代燃料。不过，由于acetoacetate与β-hydroxybutyrate均为中强酸，因此酮体产生过多时将会引起酮症（ketosis），甚至出现酸中毒 In alcholism, excess NADH shunts OAA to malate to stall TCA
50
aldolase
醛缩酶 aldolase B in fructose metabalism (F-1-P : DHAP + Glyceraldehyde) in liver heraditary deficiency (autosomal recessive) in aldolase B causes fructose intolerance ; inhibit glycogenolysis and glucogeneogenesis symptoms: hypoglycemia, jaundice, cirrhosis (肝硬化）， vomitting treatment: decrease both fructose and sucrose intake
50
Kwashiorkor
蛋白质营养不良综合征 protein-deficient MEAL: M: malnutrition E: edema A: anemia L: liver malfuction (fatty change due to decreased apolipoprotein sysnthesis)
50
kyphosis
驼背，脊柱后突 sign for homocystinuria
50
Krabbe's disease 克拉伯病
AR; deficiency in galactocerebrosidase; accumulation of galactocereboside, peripheral neuropathy, developmental delay; optic atrophy, 病理上特征行的globiod cell (脑白质中有大量球形多核细胞（球形细胞是胞内充满未降解的半乳糖脑苷脂的血源性巨噬细胞）) 主要累及脑白质，预后极差，一般1岁内死亡
51
rotenone
(鱼藤酮），inhibit Complex I (electron transport chain in mito)
52
kartagenar's syndrome (primary ciliary dyskinesia， PCD)
原发性纤毛运动障碍, AR dynein arm defect (cilia 9+2 microtub + dynein arm) - immotile cilia 反复呼吸道感染 bronchiectasis, recurrent sinusitus (鼻窦炎）， infertility (sperm运动性降低）， 常合并situs inversus (内脏转位）
53
lipoic acid
硫辛酸 PDH(glycolysis)需要的co-factor; arsenic inhibits lipoic acid: findings: vomit, rice water stool, garlic breath
54
lysosomal storage diseases (LSD) 太傻的戈谢，无法不理Neiman, 导致好好一个MD变成Crab
Tay-Sachs: 太傻，黑蒙性家族痴呆， GM2-GM3 (heXosaminidase)
55
fructose, galactose metabolism deficiency
FAB GUT fructose Aldolase B galacotose: uridyl transferase infantile cataracts; jaundice. failure to thrive, mental retardation
56
Maple syrup urine disease
AR: I love Vermont maple syrup from maple trees with branches. Blocked degradation of branched aa (Ile, Leu, Val) due to decrease of a-ketoacid DH (B1). casue i. a-Ketoacids in the blood, esp Leu severe CNS defects, retardation, and death; urine smells like maple syrup
57
start/end coden
AUG (AUAurate protein snthesis) UAA UAG UGA
59
marasmus
消瘦，消耗 M: muscle wasting loss of s.c. fat, edema
60
McArdle's disease
type V GSD, AR; M = muscle skeletal muscle glycogen phosphorylase i. glycogen in muscle, can't break down - painful cramp, myoglobinuria with strenuous exercise
61
mechanism of tetracyclin
bind to 30S subunit of ribosome, prevent attachment of aminoacyl-tRNA 阻断细菌蛋白质合成
62
antibiotics to inhibit bacterial protein synthesis
inhibit 30S subunit: 1) aminoglycosides氨基糖甙类; inhibit formation of initiation complex 2)tetracyclin: block A site (5' - EPA - 3') inhibit 50S: 3). chloramphenicol氯霉素 inhibit peptidyl transferase 4) microlides大环内酯: prevent release of uncharged tRNA after it donates its aa
63
metachromatic leukodystrophy (MLD) 异染性脑白质营养不良
AR, deficiency in arylsulfatase A (芳香基硫酸酯酶), acculmulation of cerebroside sulfate) central and peripheral demyelination, ataxia, dementia
64
function of ApoE
remnant uptake
66
niacin: 来源？缺乏引起？此病的特征？
烟酸， Vit B3, NAD+, 来源： 1） food; 2) 内源性由Try衍生，合成中需要VB6 缺乏引起pellagra(糙皮病）, pellagra3大症状：3 Ds of B3: diarrhea, dementia, dermatitis Hartnup disease(decrease Try absorption), malignant carcinoid syn (increased Try metabolism), or INH(decreased VB6)
68
Niemman-pick disease 皮包很大的女人才能去niemman marcus 买东西
AR; lysosome storage disease; deficiency in sphingomyelinase, accumulation of sphingomyelin, 犹太人多发 findings: progressive neurodegenration, hepatosplenomegaly; foam cells "soap bubble appearance of cytoplasma in the macrophages), cherry-red spots 眼底樱桃红斑 治疗：脾切除， 有胚胎肝移植成功的报道
69
collagen: 4 types Be (So Totally) Cool, Read Books
Type I (most common, 90%): B-one-, skin, tendon defective in osteogenesis imperfecta Type II: Cartilage (car-TWO-lage) Type III: reticulin - EDS (Ehlers-Danlos syn) "ThreE D) hypermobile joints, skin hyperelasticity Type IV: basement membrane or basil lamina Under the floor Alport syn
71
oxidative phosphorylation poisons
1) electron transport inhibitors: rotenone (鱼藤酮），inhibit Complex I antimycin A (抗霉素A), inhibit complex III cyanide (氰化物）， CO: inhibit complex IV 2) ATP synthase inhibitors: olygomycin (寡霉素）：inhibit complex V
72
orotic acid
乳清酸，the 1st temporary base to de novo synthesize pyrimidines
73
osteogenesis imperfecta
AD(非常少见的常显遗传病）， 1: 10,000 Type I collagen, step 3 （glycosylation) 1) multiple fractures with minor trauma, may occur during birth (confused with child abuse） 2）blue sclerae 3) hearing loss 4) dental imperfection: lack dentin
75
OTC
ornithine transcarbamoylase deficiency key E. in urea cycle； XR (urea cycle中其余的E缺乏症都是AR) carbamoyl phosphate is involved in 2 pathways: 1) pyramidine de novo synthesis (form orotic acid) 2)urea cycle OTC leads to accumulation of carbamoyl phosphate, which then is converted to orotic acid 表现：increased orotic acid in blood and urine, decrease BUN (blood urine nitrogen), sym of hyperammonemia
76
a-amanitin
Inhibits RNA pol II Cause severe hepatotoxicity if ingested
77
cholesterol metabolism
2 important enzymes: 1) HMG-CoA reductase: convert HMG-CoA to mevalonate (甲羟戊酸）； inhibited by Statins (e.g., lovastatin) 2) LCAT: lecithin (卵磷脂）-cholesterol acyltransferase: 2/3 of plasma cholesterol is esterified by LCAT
78
Phenylketones
Phenylacetate, Phenyllactate, Phenylpyruvate
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PKU
苯丙酮尿症（Phenylketonuria，PKU）是一种遗传代谢病(AR)，是由于phenylalaline hydroxylase活性降低或其辅酶四氢生物喋呤(Tetrahyrdropterin， THB)缺乏，导致苯丙氨酸向酪氨酸代谢受阻，血液和组织中苯丙氨酸浓度增高，尿中苯丙酮酸、苯乙酸和苯乳酸显著增加，故称“苯丙酮尿症”。本病虽为遗传代谢病，但并不少见，我国PKU的患病率约为1:10000,美国约为1：14 000 PKU患儿出生时大多表现正常，新生儿期无明显特殊的临床症状。未经治疗的患儿3～4个月后逐渐表现出智力、运动发育落后，头发由黑变黄，皮肤白，全身和尿液有特殊鼠臭味，常有湿疹。 mental/growth retardation, seizures, fair skin, eczema, musty body odor treat: d. Phe, i. Tyr in diet (typical) if atypical: lack THB reductase, d. domapine - i. prolactin FA考点：经典型PKU与非经典型、Albinism, alkaptonuria鉴别
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PNMT
Phenylalanine N-methyltransferase, E to convert NE to Epi
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Pompe's disease
type II GSD, AR lysosomal a-1,4-glucocidase P = pump (heart, liver, muscle) cardiomegaly, systemic findings leading to early death
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SAM
S-adenosyl-methionine, transfer methyl units (SAM the methyl donor man) regeneration of Met (and thus SAM) is dependent on VB12 and folate (VB9) required for: NE-E
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golgi 功能
1） add N-oligosaccharides on Arg 2) add O-oligosaccharides on Ser/Thr 3) add Mannose-6-phosphate on proteins for trafficking to lysosomes
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pyogenic
化脓性
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pyridoxine (VB6)
coverted to PP (pyridoxine phosphate), co-factor for transanimation (ALT, AST), decarboxylation, glycogen phosphorylase synthesis of cystathionine(胱硫醚），His, heme, niacin, neurotransmitters (serotonin, Eph, NE, GABA)注意：在homocysteine- cysteine以及succinyl-CoA - Hb过程中和VB12相关
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ketogenic nutrition
treat deficiency in alpha-ketoglutarate DH or pyruvate DH: increase lysine and leucine (Lysine and Leucine: the onLy pureLy ketogenic amino acid)
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pyruvate dehydrogenase (PDH)
pyruvate + NAD+ + CoA ⟹(PDH) Acetyl-CoA + NADH + CO2 need 5 cofactors: 1) TPP (thiamine pyrophosphate, VB1) 2) FAD(H2) from (riboflavin, VB2) 3) NAD(H) from niacin (VB3) 4) CoA from pantothenate (VB5) 5) lipoic acid (硫辛酸） Reaction happens in mito; activated by insulin in liver; inhibited by product Acetyl-CoA Arsenic inhibits lipoic acid (vomit, rice water stool, garlic breath) PDH deficiency (X-linked): increase Pyruvate and Alanine in lactic acidosis 临床表现主要是乳酸酸中毒和neurologic defects(starts in infancy) Treatment: ketogenic nutrients减少lactic acidosis (high fat, or high Leu + Lys， low protein and carbohydrate)
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ethanol过量
ethanol - (acetaldehyde 乙醛）- acetate (2 NAD+ 变成NADH): 改变pyruvate - lactate (in glycolysis); OAA - malate (TCA cycle) 导致：hypoglycemia; increased fatty acid synthesis
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pyruvate metablism pathways
4 pathways: 1) in cytoplasm: LDH - lactate 2) in cytopasm: Alanine (ALT, alanine aminotransferase; B6: carry amino groups from liver to muscle) 3) in mito: acetyl-CoA（PDH）need B1, B2, B3, B5, lipoic acid 硫辛酸 4）in mito: OAA (oxaloacetate); pyruvate carboxylase （羧化酶）/biotin
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quabain机制
bind to K+ site of Na+-K+ pump, and inhibit this pump
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rate-limiting E for cholesterol synthesis
HMG-CoA reductase (HMG-CoA to mevalonate 甲羟戊酸）; inhibited by Statins, (lovastatin) 2/3 plasma chl: esterified by LCAT (lecithin-cholesterol acyltransferase)
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beriberi
脚气病beriberi:（BerlBerl: B1 B1); dry Beriberi: affect the nervous system (polyneuritis; 多发性神经炎； symmetrical muscle wasting) wet beriberi: affect cardiovascular system )edema
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parethesias
感觉异常
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SCID
severe combined immunodeficiency disease 1 major cause is ADA（ａｄｅｎｏｓｉｎｅ ｄｅａｎｉｍａｓｅ deficiency, adenosine can't be converted to inosine): ADA\_SCID第一例人类基因疗法 excess ATP and dATP inhibit ribonucleotide reductase: inhibit DNA synthesis and lymphocyte count
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Alport Syn 机场综合症
variety of gene defects in Type IV collagen (basement membrane), XR progressive heretitary nephritis, deafness, ocular disturbance (kidney, ear, eye)
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SER功能
1）synthesize steroid H 2) detoxification of drugs and poisons cells rich in SER: liver cells; adrenal cortex
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hnRNA snRNP
hnRNA: initial transcript : destined for translation is called pre-RNA snRNP: intron splicing (s for splicing) Lupus: Ab to attack snRNP
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Urea cycle
Ordinarily, careless crappers are also frivolous about urination. ornithine + carbamoyl phosphate - citrulline - argininosuccinate - succinate + fumarate - arginine - urea
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sorbitol
a way to trap glucose inside a cell; can be converted into fructose: liver, lens, ovaries, seminal vesicles have aldose reductase + sorbital DH: glucose - (Aldose reductase) - sorbital - (DH) - fructose Schwann cells, retina and kidneys have only aldose reductase: can only convert glucose to sorbital If sorbital accumulates inside a cells: osmotic damage
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sorbitol damage
glucose (aldose reductase + NAPDH) - sorbitol - (sorbitol DH + NAD+) - fructose tissue with both E: liver, lens, ovaries, seminal vesicle tissue with only aldose reductase: schwann cells, retina, kidney (so they can't convert sorbitol to fructose and are at risk for osmotic damage: cataracts, retinopathy, peripheral neuropathy)
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Start /stop codon
AUG: Met / fMet UAA/UAG/UGA
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subluxation
半脱位, lens subluxation: sign for homocystinuria
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常见 autosomal trisomies: catch depcrw(抓住迪普卡罗）7个智障还想抓住22个聪明人
catch-22: 22q11 deletion syn d: downs (21) e: edward (election age 18; T18) p: patau (puberty age 13) c: cri-du-chat = cry of the cat （5） r: robertsonian translocation w: williams syn (7)
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Tay-Sachs disease (太傻病）
AR; deficiency in hexoSaminidase A (己糖脱氨酶A); accumulation of GM2 ganglioside(神经节苷脂); progressive neurodegeneration, developmental delay; cherry-red spots on macula, (与Neimann-pick病类似）； no hepatosplenogemaly (与Neimann-pick病不同）；
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water soluble vitamins: 9种 硫黄烟泛吡生叶，钴胺坏血九维酸 (在充满硫黄轻烟的湖上泛舟，彼岸（吡）生出莲花叶子。湖里住着9个坏血坯子。这是诡异的泸沽湖（钴胺素）才会有的景象吗？
B1（硫胺素）， B2（核黄素）， B3（烟酸）， B5（泛酸），B6(吡）， B7 （生物素）， B9 （叶酸）， B12（钴胺素）， C（抗坏血酸） 这9种水溶性维生素里，只有钴胺素和抗坏血酸不容易从体内排出，因为储存在肝脏里。 B-complex deficiency: dermatitis, glossitis, diarrhea; 皮炎，舌炎，腹泻
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cystinuria
hereditary defect of renal tubular aa transporter for cysteine, ornithine, lys and Arg, - excess cystine in the uria, precipitation of hexogonal crystals and renal staghorn autosomal recessive, common (1: 7000) treat: good hydration and urinary alkalinization
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thiamine
VB1, TPP thiamine pyrophosphate 焦磷酸硫胺素;谷物的外皮中富含 deficiency: impaired glucose breakdown (highly aerobic tissues such as brain and heart affected first. AＴＰ depletion gets worse with glucose infusion（例子：任何促进糖代谢的措施都会加重WKS); 是"ATP-B:的co-factor in decarboxylation reactions: (A: a-ketoglutarate dehydrogenase；戊酮二酸脱氢酶）Maple syrup urine disease; T: transketolase (F1P to F6P); P: pyruvate DH (pyruvate - Acetyl-CoA); B: Branched aa DH 缺乏导致脚气病beriberi:（BerlBerl: B1 B1); WKS (Wernicke's encephalopathy –Korsakoff syndrome)在慢性酗酒病人常出现，酒精会妨碍vit B1在GI吸收，以及在肝脏里的储存和活化 WE三联征：confusion, opthalmoplegia (眼肌麻痹，导致double vision), ataxia Korsakoff syndrome: acute onset of severe memory impairment， permanent(damage nucleus in thalamus) dry Beriberi: affect the nervous system wet beriberi: affect cardiovascular system,edema, high-output HF
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thiolase
乙酰辅酶A乙酰基转移酶
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uncoupling agents for oxidative phosphorylation
DNP (2, 4-dinitrophenol), overdose aspirin, thermogenin in brown fat： increase permeability of mito membrane, decrease proton gradient and increase O2 consumption. ATP synthesis stops, and electron transport continue - produce heat DNP: the most well-known uncoupling agent; used in diet pill in 1933-1938, then stopped due to toxicity
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acidic vs. basic AA
acidic: Asp, Glu (negatively charged at body pH) basic: Arg, Lys, His (他的阿精在碱性条件下溶解了） Arg and Lys are enriched in histones (positively charged, binds to negatively charged DNA); His has no charge at body pH
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uridyltransferase
尿苷酰转移酶 （UT, G-6-P to UDP-G, step in glucogenesis)
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VC
1) keep iron in Fe2+ reducing state; to facilitate iron absorption 2) collagen synthesis: step 2: hydroxylation of Proline and lysine 3) dopamine beta-hyrdroxylase: dopamine - NE
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orotic acid
乳清酸 血和尿中orotic acid increase: caused by ornithine transcarbamoylase deficiency (most common urea cycle enzyme decificency)
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beta-thalacemia mutation
Alternative splicing problem
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von Gierke's disease
GSD type I (glycogen storage disease) AR glucose-6-phosphatase ("G" for glucose phosphotase) severe fasting hypoglycemia, hepatomegaly; i.i. glycogen in liver, i. blood lactate,
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VD
skin(UV) - liver (25 hyrdroxylase) - kidney (1, 25 dihydroxylated, active form); binds to receptors in GI epithelial cells for Ca2+ absorption; and functions on osteoclasts for Ca2+ mineralization and mobilization in the presence of PTH excessive: toxic (can be stored in liver）； hypercalcemia to damage kidney deficiency: rickets in child; osteomalacia (软骨病） 表现：bone pain+ muscle weakness
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TCA summary: Citrate is Kreb's staring substrate for making oxaloacetate
citrate - cisAconitate - isocitrate - aKG (alpha-ketoglutarate)-succinyl CoA - succinate - fumarate - malate - OAA
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Why is HDL healthy?
transport Chol from peripheral tissues to liver; repository for apoC and apoE (for chylomicron and VLDL metabolism); secreted by liver and intestine
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Vit A
2 major functions: maintain epithelium; vision overdose: acute, chronic, teratogenic acute overdose: nausia, vomit, blurred vision, 颅内压升高的症状, arthalgias(关节痛）
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22q11 deletion syn
catch-22 c: cleft presentation very diverse; include: DiGeorge Syn (thymic, parathymic-第一个发现的病例有低钙血症合并先心， cardiac defects), velocardiofacial syn (软腭-心-面综合征）
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几个荧光染色用到的intermediate filaments: 分别是什么的marker? vimentin desmin cytokeratin
vimentin - connective tissue desmin (肌间线蛋白）- muscle cytokeratin (角蛋白）- epi
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trafficking proteins
COP I (向内）： retrograde Golgi - Golgi; Golgi - ER COP II (向外）：anterograde Golgi - Golgi; ER - Golgi clathrin: plasma membrane - endosome (receptor-mediated endocytosis); transGolgi - lysosome for degradation
