Biochemistry Flashcards
(94 cards)
1
Q
Biochemistry
Items needed for de novo pyrimidine synthesis
A
Aspartate,CO2,Glutamine, Phosphate
2
Q
Biochemistry
RLE for pyrimidine production
A
Carbamomyl Phosphate Synhtase II (CPS II)
3
Q
Biochemistry
Items needed for de novo purine synthesis
A
Glycine, Asprtate, glutamine, CO2, THF
“GAG” mnemonic
4
Q
Biochemistry
Orotic Aciduria
A
Inability to convert orotic acid to UMP (de novo pyriidine synthesis) because of UMP Synthase
AR
increased orotic acid in urine, megaloblastic anemia (doesnt improve with VitB12/folic acid), FTT, NO Hyperammonia
Tx: Oral uridine adminstration
5
Q
Biochemistry
RLS for purine synthesis (PRPP –> –> –> IMP)
A
Glutamine PRPP Amidotransferase
KO via 6-MP
6
Q
Biochemistry
UDP –> dUDP
A
via Ribonucleotide reductase
Inhibited by hydroxyurea
7
Q
Biochemistry
Carbamoyl pohphsate
A
Involved in 2 metabolic pathways
- De novo pyrimidine synthesis
- Urea cycle
8
Q
Biochemistry
dUMP –> dTMP
A
Thymidylate Synthase, inhibited by 5-FU (analog of uracil)
9
Q
Biochemistry
DHF –> THF
A
Diydrofolate reductase, inhibited by MTX (euk) and TMP (Prok)
10
Q
Biochemistry
Advantages of Purine Salvage Pathway
A
Reutilizes nucleotides,
prevents loss of ATPs needed for de novo purine synthesis,
neuclotides formed in this pathway inhibit de novo pathway at RLS
Decreased uric acid formation - end product of purine catabolism.
11
Q
Biochemistry
HGPRT
A
Needed for conversion of Guanine to GMP and hypoxanthine to IMP
LESCH NYHAN Syndrome; X-linked Recessive
KO causes defective purine salvage, wth excess uric acid prdxn and de novo purine synthesis
Retardation, self mutilation, aggression, hyperuricema, gout,choreathetosis:
tx; allopurinol
12
Q
Biochemistry
Cause of SCID
A
Adenosine deaminse deficienecy, needed for conversion of adenosine to inosine
Causes impaired DNA synthesis and hence decreased lymphocyte count
AR
13
Q
Biochemistry
Nucleotide excision vs base excision vs mismatch repair
A
Nucleotide and BER = late damage, 1. NER is for bulky damage/pyrimidine dimers (xerdoerma pigmentosum)
2. BER is for damaged bases
- Early damage, can lead to HNPCC
14
Q
Biochemistry
Immunohistochemical stains for intermediate filaments:
- Vismentin
- Desmin
- Cytokeratin
- GFAP
- Neurofilaments
A
- Connective tissue
- Muscle
- Epithelial cells
- Neuroglia
- Neurons
15
Q
Biochemistry
Metabolism in:
- Mitochondria
- Cytoplasm
A
Mitochondria: Fatty acid oxidation, acetyl CoA production, TCA cycle, oxidative phosphorylation
Cytoplasm : fatty acid synthesis, HMP shunt, protein synthesis, steroid synthesis, cholesterol synthesis
Both: Heme synthesis, Urea Cycle, Gluconeogenesis (HUGs take two (both))
16
Q
Biochemistry
Kinase Phosphorylase Phosphatase Dehydrogenase Carboxylase
A
- Uses ATP to add high energy phosphate group onto substrate
- adds inorganic phopshate without ATP
- removes phosphate group
- catalyzes oxidation/reduction reactions
- transfers CO2 groups with help of biotin
17
Q
Biochemistry
RLS glycolysis
A
Phosphofructokinase 1
+ : AMP, fructose 2,6 BO
- : ATP, citrate
18
Q
Biochemistry
RLS Gluconeogenesis
A
Fructose 1,6 Bisphosphatase
+: ATP
- : AMP, fructose 2,6-BP
19
Q
Biochemistry
RLS TCA cycle
A
Isocitrate dehydrogenase
+ : ADP
- : ATP, NADH
20
Q
Biochemistry
Glycogen synthesis RLS
A
glycogen synthase
+: glucose, insulin
-: epinephrine, glucagon
21
Q
Biochemistry
Glycogenolysis RLS
A
Glycogen phosphorylase
+ : EPI, Glucagon, AMP
- : Insulin, ATP
22
Q
Biochemistry
RLS HMP Shunt
A
Glucose 6P Dehydrogenase
+ : NADP
-: NADPH
Deficient in G6PD deficiency, causing hemolytic anemia
23
Q
Biochemistry
De novo pyrimidine synthesis RLS
A
Carbamoyl phosphate synthetase II (CPS II)
24
Q
Biochemistry
De novo purine synthesis RLS
A
Glutamine-PRPP amidotrnasferase
-: AMP, IMP, GMP
25
# Biochemistry
Urea Cycle RLS
Carbamoyl Phosphate synthetase I
+: N acetylglutamte
26
# Biochemistry
Fatty acid oxidation RLS
Carnitine acyltransferace I
+: insulin, citrate
-: glucagon, palmitoyl CoA
27
# Biochemistry
Fatty Acid Oxidation RLS
Carnitine acyltrnasferase I
-: Malonyl-CoA
28
# Biochemistry
Ketogenesis RLS
HMG-CoA synthase
29
# Biochemistry
Cholesterol synthesis RLS
HMG-CoA reductase
+: insulin, thyroxine
-: glucagon,cholesterol
target of statins
30
# Biochemistry
NADPH is a product of and is used in :
HMP Shunt
- Anabolic processes
- respiratory burst
- P450
- Glutathione reductase
31
# Biochemistry
Hexokinase vs. Glucokinase
Glucose --> Glucose -6 - phosphate
- Hexokinase: high affinity (low Km) for glucose (can continue when blood glucose is low), low capacity (low Vm), feedback inhibited by product, fond in all tissues
- Glucokinase: lower affinity for glucose (high Km) but high capacity (high Vmax), induced by insulin, found in regulatory cells like liver and pancreas. Hence at higher concnetrations, glucose is stored in liver
32
# Biochemistry
Glycolysis:
| 3 regulatory enzymes
1) Hexokinase/glucokinase
2) PFK1
3) Pyruvate kinase (+F16BP, -ATP, -alanine)
33
# Biochemistry
Key enzymes for gluconeogenesis
1) Pyruvate carboxylase
2) PEP carboxykinase
3) Fructose 1,6 bisphosphatase
4) Glucose-6-phosphatase
34
# Biochemistry
Regulation by Fructose 2,6, bisphosphate
Fed state: + insulin, F26BP is promoting conversion of F6P to F16BP towards glycolysis via PFK-1 (more glycolysis)
Fasting state: +glucagon, F26BP is promoting conversion of F6P towards gluceoneogenesis (less glycolysis)
35
# Biochemistry
Pyruvate Dehydogenase Complex
"Tender loving Care for Nobody"
-B1, B2, B3, B5, lipoic acid
(Thiamine, lipoic acid, CoA, FAD, NAD)
Pyruvate --> Acetyl CoA
36
# Biochemistry
Pyruvate Metabolism's different roles
1) Alanine aminotransferase (alanine created, carries amino groups to liver from muscle)
2) Pyruvate carboxylase (oxalacetate created, can replenish TCA cycle or be used in gluconeogenesis
3) Pyruvate dehydogenase (Acetyl CoA created, transition from glycolysis to TCA cycle)
4) Lactic acid dehydrogenase (lactate created, end of anaerboic glycolysis)
37
# Biochemistry
GLUT transporters
Glut1: RBC, BBB - low level basal rate
Glut2: hepatocyte/pancreas, small intestines, kidneys, important for regulation, highest Km
Glut3: neurons/placenta
Glut4: Skeletal/adipose tissues (requires insulin)
Gllut5: speratocytes and GI tract (fructuse transport)
38
# Biochemistry
Fabry Disease
XLR
Deficient in alpha galactosidase
accumulates ceramide trihexoside
Sx: angiokeratomas, cardiac, and renal involvement, painful neuropathy
39
# Biochemistry
Gaucher Disease
Lysosomal Storage disease : deficiency of beta-glucosidase . Affects bone, liver, spleen, bone marrow and brain. Pancytopenia, bone fractures, joint pain "Crinkled paper" bone marrow cells .
AR
40
# Biochemistry
Hurler syndrome
autosomal recessive
lysosomal storage disease
deficiency of a-L-iduronidase - accumulation of mucopolysaccharides heparan sulfate and dermatan sulfate in heart, liver, brain, and other organs
gargoylism, corneal clouding, hepatosplenomegaly, developmental delay
41
# Biochemistry
Hunter syndrome
XLR
Enzyme: Iduronate sulfatase
Buildup: Dermatan & heparan sulfate
gaygoylism, hepatosplenomegaly, developmental delay (no corneal couding like Hurler)
42
# Biochemistry
Niemann Pick Disease
AR
Def: Sphingomyelinase
Accumulation of spingomyelin
Sx: hepatosplenomegaly,cherry red spot in macula,foam cells, progressive neurodegeneration
43
# Biochemistry
Tay Sachs Disease
AR
Def: B hexosaminidase
Excess GM2 ganglioside builds up
Chery red spot in macula,progressive neurodegeneration, no hepatoslenomegaly
44
# Biochemistry
Krabbe's Disease
- AR
- Galactrocerbrosidase deficiency
-buildup of galactosyl sphingosine and galactrocerbroside
Progressive neurodegeneration, developmental delay, optic atrophy, large globiod bodies in brain and white matter, fatal early in life, seizures
45
# Biochemistry
Metachromic Leukodystrophy
AR
Arylsulfatase A deficiency. Sulfatides (cerebroside sulfate) ; Accumulates cerebroside sulfate ( glycolipid of myelin ) in CNS & PNS --demyelination - UMN/LMN sx, periph neuropathy. ataxia, dec attention span
Late infantile form within 1 year spastic quadriplegia, blind, dementia, seizures, death by 5-6y.
46
# Biochemistry
Collagen subtypes and associated disesase
Type 1 - bones, scar, tendons, ligaments (Def: osteogenesis imperfecta)
Type 2 - cartilage, nucleous pulposis
Type 3 - reticular (granulation, skin, blood vessels, lymphatics, BM (def causes Ehlers Danlos syndrome)
Type 4 - basement membrane (Alport syndrome)
Be So Totally Cool Read Books
47
# Biochemistry
Essential, Acidic, Basic Amino Acids
Essential (needed in diet): MVH(glucogenic), IFTW(both), LK(ketogenic)
Acidic: Asp, Glu
Basic: Arg, Lys, His.
PVT TIM H a LL
48
# Biochemistry
amino acid derivatives
| Tryptophan, histidine, phenylalanine, glycine, arginine, glutamate
- Niacin, serotonin (tryptophan)
- histamine ( histidine)
- epinephrine, norepinephrine, dopamine, Dopa, thyroxine ( Phenylalanine --> tyrosine)
- Heme (glycine)
- Creatinine, urea,NO (arginine)
- GABA, glutathione (glutamate)
49
# Biochemistry
ALT, AST
ALT: Alanine + aKG Glutamate + pyruvate
AST: glutamate + oxaloacetate aKg + aspartate
50
# Biochemistry
Von Gierkes Disease
Deficiency in Glucose-6-phosphatase, therefore cell cannot release glucose from glycogen for gluconeogenesis.
Findings: Severe fasting hypoglycemi, increased glycogen in liver, increased blood lactate, hepatomegaly, kidneymegaly, enterocytemegaly
AR, Tx: feedfrequently
51
# Biochemistry
Pompe's Disease
Type II Glycogen Storage Disease
Lysosomal alpha-1,4-glucosidase deficiency
finginds: cardiomegaly and systemic findings leading to early death
***Pompe's trashes the pump...heart, liver and muscle
52
# Biochemistry
cori's disease
glycogen storage type III
deficiency of debranching enzyme - a-1,6-glucosidase
milder form of type I with normal blood lactate
gluconeogenesis intact
AR
53
# Biochemistry
McArdle's Disease
glycogen phosphorylase deficiency (glycogen storage disorder V) in the skeletal muscle
AR,
Sx: fatigue and cramps, myoglobinuria
forearm ischemia test is abnormal
increased glycogen in muscle that cant be broken down
Muscle cells swell and lyse bc of H2O, causing rhabdomyolysis
54
# Biochemistry
Metabolic fuel use during exercise
After seconds: stored ATP then creatine phosphate
After minutes: anaerobic glycolysis
After hours: Aerobic metabolism and FA oxidation
55
# Biochemistry
Fasting and starvation
```
fed state (After meal) : Glycolysis/aerobic resp
fasting (bw meals) hepatic glycogenolysis (major, hepatic GNG, adipose release FFA (minor)
```
Starvation days 1-3 : hepatic glycogenolysis (up to 24 hrs), Adipose release FFA , Muscle and liver use FFA , Hepatic GNG from lactate/alanine, and fr adipose glycerol and propionyl coA (from odd chain FFA)
Starvation after 3 days: Adipose stores ( ketone bodies major source of energy for brain and heart)--fat people live longer. After these are depleted, v ital protein degradation accelerates-->organ failure and death.
56
# Biochemistry
Lipid Transport
LDL-cholesterol from liver to tissues
HDL-transport cholesterol from periphery to liver
VLDL-deliver TGs to peripheral tissue
IDL-byproduct when VLDL degraded in serum, delivers TGs and cholesterol to liver
57
# Biochemistry
major apolipoproteins
- E = mediates remnant uptake (on all)
- AI = activates LCAT (on HDL)
- CII = LPL cofactor (on CM and VLDL)
- B48 = mediates CM secrection (on CM and CM remnant)
- B100 = binds LDL R (on VLDL, IDL, LDL)
58
# Biochemistry
Lipoprotein functions
Lipoproteins are composed of varying proportions of cholesterol, TGs, and phospholipids. LDL and HDL carry most cholesterol. LDL transports cholesterol from liver to tissues. HDL transports cholesterol from periphery to liver.
59
# Biochemistry
Lipoprotein Functions (CM,VLDL, IDL)
- CM: Delivers dietary TGs to peripheral tissues and choelsterol to the liver as a CM remnant (which are depleted of triacylglycerols), secreted GI Epi cells
- VLDL: Delivers hepatic TGs to peripheral tissues; secreted by liver
- IDL: FOrmed in degredation of VLDL, delivers TGs and cholesterol to the liver
60
# Biochemistry
Lipoprotein Functions (LDL, HDL)
- LDL: Delivers hepatic cholesterol to peripheral tissues; formed by hepatic lipase modification of IDL in peripherl tissues, taken up by receptor mediated ednocytosis
- HDL: Mediates cholesteral transport from periphery to liver; is respository for apoC and apoE. Secreted from liver and intestines
61
# Biochemistry
Hyperchylomicronemia
Type I familial dyslipidemia
- due to lipoprotein lipase deficiency or altered apolipoportein CII
→ increased chylomicrons and elevated blood levels of TGs and cholesterol
→ pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas (NO ↑ risk of atherosclerosis)
62
# Biochemistry
Familial hypercholesterolemia
1. Autosomal dominant disorder
2. Missing or decreaed receptors for LDL in liver
3. Negative feedback fails, results in high LDL and cholesterol Serum
4. accelerated atherosclerosis, tendon xathnomas, corenal arcus
63
# Biochemistry
Hypertriglyceridemia
Increased blood VLDL and TG
AD
Hepatic overprodxn of VLDL
Causes pancreatitis
64
# Biochemistry
Abetalipoproteinemia
-Autosomal recessive
-No apoB48 or apoB100 (hence decreaedCM and VLDL synthesis/secretion)
-Fatty enterocytes on intestinal bx
Findings: -Acanthocytosis of RBCs, Failure to thrive, ataxia, night blindness
Decreased Vit A, D, E, K
-Treat with vitamin E
65
# Biochemistry
Lesch-Nyhan Syndrome
Defective purine salvage due to absence of HGPRT. Results in excess uric acid production .
Findings: retardation, self-mutilation, gout, aggression.
66
# Biochemistry
B12 vs. Folate Deficiency
- B12 Deficiency is usually accompanied by elevated concentrations of blood homocysteine and methylalonic acid
- Folate deficiency results in only elevated homocysteine
-folate deficiency does not cause neuro sx
Test for IF in blood (signifies B12 deficiency)
67
# Biochemistry
arsenic toxicity
inhibiting lipoic acid (binding to the SH-group)
* Vomiting
* Rice water stools
* Garlic breath
Needed for PDH and OAA complex
68
# Biochemistry
Key enzymes in Glycolysis
1) hexokinase/glukokinase
2) PFK1 (RLS)
3) Pyruvate kinase
69
# Biochemistry
Key Enzymes in gluconeogenesis
1. Pyruvate carboxylase (req B7)
2. PEP carboxylase
3. Fructose 1,6 Bisphophatase (RLS)
4. Glucose 6 Phosphatase (absent in muscle cells)
Occurs primarily in liver. Enzymes found also in kidney,gi epi. Def of enzymes causes hypoglycemia. Odd chain fatty acids yields propionyl CoA which can enter TCA cycle and undergo gluconeogneis
70
# Biochemistry
Pyruvate dehydrogenase complex deficiency
=backup of substrate (pyruvate, alanine), lactic acidosis, most cases due to X-linked mutation in E1-a but can also be due to cofactor deficincies
sx: neurologic defects, usually starting in infancy
tx: increased intake of ketogenic nutrients (high fat contant, high lysine/leucine)
71
# Biochemistry
Key TCA Cycle enzymes
1. Citrate synthase
2. Isocitrate dehydogenase (RLS)
3. alpha ketoglutarate dehydrogenase
72
# Biochemistry
Oxidative Phosphorylation Poisons
Electron Transport Inhibitors - directly inhibit electron transport, causing a decrease in the proton gradient and blocks ATP synthesis. Ex: Rotenone, CN - , antimycin A, CO.
ATPase Inhibitors - directly inhibit mitochondrial ATPase, causing an increase in the proton gradient. No ATP is produced because electron transport stops. Ex: Oligomycin
Uncoupling Agents - increase permeability of the membrane, causing a decrease in proton gradient and increase in oxygen consumption. ATP synthesis stops, but electron transport continues. This produces heat. Ex: 2,4-DNP, ASA, thermogenin in brown fat.
73
# Biochemistry
HMP Shunt (pentose phosphate pathway)
Provides source of NDAPH from G-6-phoshpate
1. Glucose 6 Phosphate dehydregnase is RLS enzyme
74
# Biochemistry
HMP Shunt (pentose phosphate pathway)
Provides source of NDAPH from G-6-phoshpate
1. Glucose 6 Phosphate dehydregnase is RLS enzyme
75
# Biochemistry
Enzymes of Respiratory (oxidative) Burst
1. NADPH Oxidase ( def = Chronic Granulomatous Dz)
2. Superoxide Dismutase
3. Myeloperoxidase
4. Glutathione Peroxidase
5. Glutathione Reductase
6. G6PD (deficiency causes G6PD deficiency, PNH)
- first 3 are in phagolysosome
- last 3 are in neutrophil cytoplasm
76
# Biochemistry
Essential Fructosuria
Involves a defect in fructokinase . Autosomal recessive. A benign, asymptomatic condition since fructose does not enter cells
Symptoms: fructose appears in blood and urine (osmotic diuresis)
Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism
77
# Biochemistry
Fructose intolerance
* Hereditary deficiency of aldolase B . Autosomal recessive. Fructose-1-phosphate accumulates ⇒ ⇓in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.
* Symptoms → hypoglycemia, jaundice, cirrhosis, vomiting.
• Tx → ⇓intake of both fructose and sucrose (glucose + fructose).
78
# Biochemistry
Galactokinase deficiency
Hereditary deficiency of galactokinase. Galactitol accumulates if galactose is present in deficiency diet. Relatively mild condition. Autosomal recessive. Symptoms: galactose appears in blood and urine, infantile cataracts. May initially present as failure to track objects or to develop a social smile.
79
# Biochemistry
Classic galactosemia
- absence of galactose-1-phosphate uridyltransferase
- autosomal recessive
- more severe than galactokinase deficiency
- accumulation of galactitol and other toxic intermediates
- failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
- Tx: exclude galactose and lactose from diet
80
# Biochemistry
Urea Cycle Key Enzymes
1. CPS 1 (RLS)
| 2. Ornithine Transcarbamoylase
81
# Biochemistry
Ornithine Transcarbamoylase (OTC) deficiency
most common urea cycle disorder
X-linked recessive
often evident in first few days of life but may be late onset (girls)
Findings: orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia
82
# Biochemistry
Ornithine Transcarbamoylase (OTC) deficiency
most common urea cycle disorder, interferes with ability to elimate ammonia, excess carbamoyl phopsphate convereted to orotic acid
X-linked recessive
often evident in first few days of life but may be late onset (girls)
Findings: orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia
83
# Biochemistry
Phenylketonuria
Autosomal recessive; decreased p henylalanine hydroxylase or tetrahydrobiopterin cofactor (malignant/atypical PKU); tyrosine becomes essential (does not help atypical PKU);
Findings: mental retardation, growth retardation, seixures, ecxema, musty/mousy body odor;
Tx: decreased Phe and increased Tyr in diet
84
# Biochemistry
Alkaptonuria
- deficiency of homogentisic acid oxidase in degradative pathway of TYROSINE to fumarate
- formation of alkapton bodies=> dark urine and dark CT, brown pigmented sclera
(homogentisic acid toxic to cartilage)
AR, benign
85
# Biochemistry
Homocystinuria (3 types)
3 forms (AR; excess homocysteine; cysteine becomes essential): 1. Cystathionine synthase deficiency- (tx: decrease Met and increase Cys, B12, and folate in diet) 2. Decreased affinityof cystathionine synthase for pyridoxal phosphate (increase Vit B6 in diet) 3. Homocysteine methyl transferase (requires B12) deficiency
86
# Biochemistry
Homocystinuria (findings)
Findings: increased homocysteine in urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (down and in) and atherosclerosis (stroke and MI)
All due to excess homocysteine and cysteine becoming essential
87
# Biochemistry
Cystinuria
* ↓ tubular reabsorption of cystine
* inherited deficiency of COAL transporter (cystine,ornithine, lysine, and arginine) in PCT
* AR, tx with good hydration and alkalization (acetazolamide)
88
# Biochemistry
Maple syrup urine disease
- Blocked degradation of branched amino acids(Ile, Leu, Val) due to ↓ α-ketoacid dehydrogenase. - Causes ↑ α-ketoacids in the blood, especially Leu.
- C auses severe CNS defects, mental retardation, and death.Urine smells like maple syrup.
89
# Biochemistry
Hartnup Disease
AR defect in neutral amino acid transporter on renal and intestinal epithelial cells
Causes tryptophan excretion in urine and decreased absorption from gut, leading to pellagra
Pellagra (remember tyrosine is needed to make niacin, serotonin, melatonin
90
# Biochemistry
Alanine cycle and cori cycle
Alanine cycle: Pyruvate to alanine by ammonium in muscle. Goes to liver, NH3 taken by aKetoglutarate, alanine back to pyruvate which is used to make glucose.
Glucose cycle: Glucose in muscle is broken down. Pyruvate can be used in alanine cycle, Lactate exits muscle back to liver, where gluconeogenesis occurs
91
# Biochemistry
key enzymes in glycogen metabolism
glycogen synthase
(glycogenesis) - RLS
glycogen phosphorylase
(glycogenolysis)
92
# Biochemistry
What 2 enzymes are key to the coordination of Fatty Acid metabolism?
1. Acetyl-CoA carboxylase (synthesis)
| 2. Carnitine palmitoyl trnasferase/acyltransferase I (degradation)
93
# Biochemistry
Carnitine Deficiency
Can't transport long-chain-fatty-acids into mitochondria=tox accumulate
Sx: weakness, hypotonia, hypoketotic hypoglycemia
94
# Biochemistry
Ketogenesis and cholesterol synthesis RLS
Hmg CoA Synthase (ketogenesis)
HmGCoA Reductase (cholesterol genesis) ==> TARGET FOR STATINS
