molecular medicine block 4 Flashcards
(174 cards)
1
Q
4 main classes phospholipids
A
phosphatiylcholine
phosphatidylethanolamine
phosphatidylserine
sphingomyelin
2
Q
glycerophospholipids (phosphatidyls)
A
glycerol backbone
2 fatty acids
phosphorylated head group
3
Q
ether glycolipids
A
glycerol ether backbone
1 fatty acid
phosphorylated head group
4
Q
sphingomyelin
A
sphingosine backbone
1 fatty acid
phosphorylated head group
5
Q
glycerophospholipid synthesis
A
phosphatidic acid to
diacylglycerol to
glycerophospholipids (use CTP and head group)
OR
phosphatidic acid to
CDP-diacyl glycerol (using CTP) to
glycerophospholipids (using head group)
-slightly different for different lipids
6
Q
head groups can be converted to what
A
enzymes
7
Q
cardiolipin is what
A
a dimer
headgroup is phosphatidylglycerol
CDP-diacylglycerl to
cardio lipin (using phosphatidylglycerol)
OR
CDP-diacylglycerol to phosphotidlinosital (using inositol)
8
Q
ether glycolipids
A
DHAP joins fatty acyl CoA (ester bond)
exchanged with fatty alcohol (reduced FA)
ketoreduced to hydroxyl, fatty acid added, dephosphorylated
add head group, desaturate, get plasmalogen
9
Q
plasmalogen
A
ethanlamine in myelin
choline in heart
platelet activating factor (choline acetyl not FA, saturated alkyl group) deficient in Zellweger syndrome
10
Q
glycerophospholipds degraded
A
by phospholipases - A1/2 remove FAs, C removes phosphorylated head groups, D removes head groups
11
Q
sphingolipids
A
nervous system and binding sites
-serine and palmitoyl CoA condense, reduce keto to hydroxy, add FA and amino, desaturate palmitate
-choline for sphingomyelin, galactose/glucose for cerebrosides, sialic acid for gangliosides, sulfate for sulfatides
12
Q
add sulfate
A
need activated donor PAPs (AMP wiht sulfate on phophate), add phosphate to 3’ C
13
Q
surfactant
A
reduces pressure to inflate alveoli
made of dipalmitoylphosphatidyl choline/phosphatidylglycerol/apoproteins Sp-a,b,c/ cholesterol
phosphatidylcholine increases at 35 weeks pregnant
14
Q
eicosanoid synthesis
A
start with essential fatty acid
mostly made from arachadonic acid (cleaved from membrane phospholipids, modified, short half lives)
15
Q
eicosanoids cleaved
A
from 2 position in lipids
cleaved by phospholipase A2
other paths use phospholipase C (cleave from DAG portion)
16
Q
3 paths of synthesis which lead to what
A
lipoxygenase
cytochrome P450
cyclooxygenase
17
Q
cyclooxygenase synthesis
A
4 oxygen atoms added to acid yielding PGC2
peroxidase and 2 gluthione reduce endoperoxide at 15 to get PGH2
source of prostoglandins, prostacyclins, thromboxanes
18
Q
prostoglandins
A
5 membered ring with subsituents on 9/11 C and OH on 15
class determined by ring substituents
subtypes indicate the number of double bonds determined by the FA
vascular/respiratory/immune defects
19
Q
cyclooxygenase inhibition
A
aspirin (irreversible), NSAIDS, selective inhibitors have side effects problem
aspirin leads to ulcers because decreased protective prostoglandin effects
19
Q
thromboxanes
A
thromboxane A synthase in platelets
oxygen links 9/11C, other in ring between 11/12
aggregation of platelets and clotting
19
Q
COX 1
A
produced constituitively in most tissues
only form in mature platelets, gastric protective effect
20
Q
COX 2
A
immune response
cytokines and growth factor elevate expression
inhibitors only affect inflammatory response
21
Q
Cyclooxygenase inhibitors use what kind of receptor
A
G protein
different for different classes
some cell type specific
22
Q
fatty acid synthesis
A
glucose to
citrate to
acetyl CoA to (using acetyl coa carboxylase *rate limiting where phosphorylated=inactive)
malonyl CoA (attached to B5 on acyl carrier protein moeity of complex) to
palmitate to
palmitoyl CoA
malonyl CoA to palmitoyl CoA uses fatty acid synthase to add 2 C units at a time
23
malonyl CoA inhibits what
futile cycling
24
fatty acid elongation
in ER
malonyl CoA produces 2 Cs
keto to hydroxy double bond requires 2 NADPH
25
desaturating FAs
in ER
reduces O to H2O
NADH reduces reductase (cytochrome B5) which acts with desaturase
26
arachidonic acid
precursor of prostoglandin (made from essential FA linoleate)
desaturated, elongated, desaturated
3 enzymes needed
27
triaclglyceral exported in how
in VLDL by liver to muscle or adipose
28
TAG storage in FED state
glucose and fatty acids turned to triglycerides
29
TAG in FASTED state
triglycerides converted to fatty acids or glycerol by lipases (phophorylated active)
30
adipose hormones
leptin and adiponectin
31
leptin
JAK/STAT signaling
hypothalamus make factors that decrease food intake
32
adiponectin
AMPK stimulates glucose/FA oxidation
stimulates PPAR which is similar
low expression in obesity
33
cholesterol structure
4 rings, C above 17 outside ring (20-27 side chain), 1 hydroxyl at 3 C (hydrophilic)
34
cholesterol functions
cell membranes, converted into steroids, bile acids/salts, derived from it, vit D synthesized from it
35
cholesterol synthesis
starts with acetyl CoA
lots of enzymatic reactions
4 stages
1. mevalonate
2. activated isoprenes
3. squalene
4. cholesterol
36
acetyl CoA to mevalonate
intermediates - acetyl CoA and HMG CoA
use HMG CoA synthase (regulated)
HMG CoA reductase (committed step) phosphorylated = inactive
transcriptional regulation
37
mevalonate to isoprenes
uses 3 ATP
isoprenes isomerize
38
isoprenes to squalene
2 isoprenes join geranyl phosphate
another isoprene makes farnesyl pyrophosphate
2 join to make squalene
39
squalene to cholesterol
epoxide formation (NADPH, O2)
rings and epoxide form hydroxide (lanosterol first with steroid nucleus)
many more steps
40
bile salts
fat digestion (detergent action)
41
bile acid synthesis
cholesterol to (using 7 alpha hydroxylase *rate limiting)
7 alpha hydroxycholesterol to
cholic acid and chenodeoxycholic acid (differ in hydroxylation)
-conjugated by AAs to decrease pKa and ionized in lumen of gut
42
transported by lipoprotein particles
TGs, PLs, cholesterols and cholesterol esters
43
transported by albumin
free fatty acids
44
lipoprotein
lipid transport particle
core nonpolar
phospholipids, cholesterol, apolipoprotein (amphipathic) on surface
45
chylomicrons
transport dietary fat from intestins
46
VLDLs
transport endogenous fat from liver (Apo B100)
47
LDLs
cholesterol to liver and tissues
48
HDLs
cholesterol from membrane in tissues to IDLs
49
structural scaffold apolipoproteins
Apo B48 and Apo B100
50
apolipoproteins that activate enzymes and enzyme receptors
Apo A1 Apo E and Apo C 2
51
chylomicron remnants taken up by liver by recognizing what
Apo E
52
VLDL becomes what
VLDL remnant (taken up by liver with Apo E) or IDL (metabolized to LDL)
53
LDL taken up by liver and tissues
excess taken up by macrophages and produce build up
54
LDL receptor endocytosis
receptor binds Apo B100
55
endocytosed cholesterol
into membrane
stored as cholesterol ester
used for biosynthetic purposes and regulatory signaling
56
synthesis of cholesterol esters
by ACAT in tissues and LCAT in blood
57
HDL
donates Apo C2 and Apo Eto chylomicrons and VLDLs
picks up cholesterol and delivers it to VLDLs and IDLs by LCAT and CETP
LCAT stimulated by ApoA1 in HDL
CETP exchanges cholesterol ester for TGs
58
inborn errors of metabolism
most autosomal recessive, most due to defects of single genes that code for enzymes that facilitate conversion of various substances
59
frequent cause of
sepsis like symptoms, intellectual disabilities, seizures, sudden infant death, neurologic impairment
60
when identified
consult genetecist
61
long term management
frequent surveillance, diet, medicine adjustment, best with center familiar with IEMs
62
newborn screenings
5 drops of blood on filter paper
use tandem repeat mass spectrometry
false negative if tested too early or transferred
63
classifications of IEMs
carbohydrate disorders
AA dsorders
urea cycle defects
FA oxidation (lipid) disorders
mitochondrial (energy production) disorders
organic acid metabolism
64
acute presentations
errors in breaking down food - hypoglycemia
errors interfering with excreting metabolites - intoxication (encephalopathy)
errors with FA oxidation - hypoglycemia and acidosis
glycogen storage diseases not generally present actively
65
severe errors in carb matabolism
present early (neonatal perior) and catastrophic
66
severe errors in exretion
present with intoxication (elevated ammonia)
67
severe errors in accessing stored energy
may be asymptomatic as long as ongoing intake of carbs
68
body odor correlations
musty/mousy = PKU
boiled cabbage = tyrosinemia, hyperthioninemia
maple syrup = maple syrup urine disease
rotting fish = trimethylaminuria
sweaty feet = isovaleric acidemia, glutaric academia (type 2)
69
IEMs should be considered in differential with what present
neurologic AND GI findings
70
treatment syndromes with toxicity
removal of toxic compounds
enhance deficient enzymes
provide missing product
prevent and reverse catabolism during times of stress
in sepsis or shock giv enothing by mouth, give pure substrate, if high nitrogen give scavengers
71
galactosemia
deficient in galactose 1 phosphate urididyl transferase
cant breakdown galactose
cataracts, acidosis, poor feeding
treat with elimination of dietary galactose
72
phenylketonuria
cant convert phenylalanine to tyrosine
absent or reduced phenylalanine hydroxylase
elevated phenylalanine disrupts brain
guthrie test for newborns
treat with diet restricted in phenylalanine
73
maple syrup urine disease
deficient in decarboxylase which initiation of keto acid analogs of branched chain AAs (leucine, isoleucine, valine)
leucine crosses blood brain barrier
treat with restriction of the AAs
74
homocystinuria
deficiency of cystathioining beta synthase
homocysteine accumulates in blood and appears in urine
enhanced reconversion homocysteine to methionine leads to elevated methionine
treat with folate, B6, B12, low methionine, give betaine
75
hereditary fructose intolerance
deficient in fructose 1,6 bisphosphate aldolase (aldolase B)
cant breakdown fructose
avoid food that is noxious
76
von gierke disease
defect in glucose 6 phophatase
glucose cant be made from glycogen in liver
77
MCAD deficiency
medium chain acyl coenzyme A dehydrogenase deficiency
episodic hypoglycemia after fasting
FA intermediates accumulate, insufficient ketone bodies, glycogen gone
treat with usable calories promptly
78
congenital adrenal hyperplasia
mutations in cortisol synthesis
overproduction of cortisol precursors and adrenal androgens
aldosterone deficiency leads to loss of salt
treat by replacing cortisol, supress adrenal androgen secretion, replace mineralcorticoids
79
zellwegger syndrome
severe peroxisome biogenesis disorder
mutations in proteins needed for peroxisome biogenesis and importing proteins into matrix
neonatal hypertonia, progressive white matter disease, distinct face, death in infancy
80
lysosomal storage disorders
materials accumulate in tissues leading to cell, tissue, organ disfunction
most enzyme defects but some defects in transport or targetting
81
mocopolysaccharidoses
reduced degradation of glycosaminoglycans
10 enzymes cause 6 disorders which are all similar but can be distinguished
autosomal recessive except for Hunter (Xlinked)
mental development issues in Hunter, Hurler, Sanfillipo
82
sphingolipidoses
lysosomal storage diseases (mucolipidoses)
sphingolipid degredation deficient
Gaucher, Tay Sachhs, Niemann Pick
83
I cell disease
mucolipidosis 2 (MLS 2)
phospshotransferase deficient
cant transport to lysosome, accumulate as inclusions
84
urea cycle disorders
5 major reactions and defects in all are known
defects in 4 lead to accumulation of precursors
carbamoyl phosphate synthase
ornithine transcarbamoylase (OTC)
argininosuccinate synthase
argininosuccinase
85
OTC deficiency
X linked
10 exons carry variety of mutations
women can be symptomatic carriers
86
energy production issues
several paths to energy production with various substrates
lead to OXPHOS system (5 multisystem complexes in inner mitochondrial membrane)
phenotypes complex
87
transport system issues
move molecules btwn compartments
protein transporters for AAs, glucose, metal ions
same transporter may be used in different tissues
88
cystinuria
type 1 mutates SLC3A1
type 2 mutates SLC7A1
heavy and light chains of brush border AA transport B vitamins
less transpor, less AA recoverd, more in urine (lead to kidney stones)
89
metal ions transporters
defects for copper, iron, zinc known
can be in or out of cell
disorders due to deficiency or excess
different cell types, different transporters, different diseases
90
wilson disease
defect in copper excretion to biliary tract
accumulates in liver leading to progressive liver disease and neurological abnormalities
gene known as ATP7B
91
hereditary hemochromatosis
excess iron absorption in intestine
accumulates in liver, heart, joints
delayed onset and incomplete penetrance
diagnose with liver biopsy with hemosiderin staining
genetics 1 - linkage to MHC region (gene called HFE), gene product normally inhibits iron uptake so disruption reduces negative feedback so more is absorbed
genetics 2 - mutation C282Y, cystein to tyrosine mutation, selective advantage heterozygote, reduce domain
92
heme
porphyrin ring structure
binds fe
synthesized from glycine and succinate in cytochromes
defects cause porphyrias
93
heme synthesis
glycine and succinyl CoA to delta aminolevulinate
2 delta aminolevulinate to porphobilinogen
4 porphobiligin to hydroxymethylbilane
linear hydroxymethylbilane to cyclicporphyrinogen 3
side chains converted, iron added to make heme
94
heme synthesis 2
delta ALA synthase uses glycine and succinyl CoA to delta ALA
2 delta ALA convert to porphobilinogen
heme represses delta ALA synthase activity and synthesis
95
delta aminolevulinic acid dehydratase and ferrochelatase inhibited by
LEAD
96
heme degradation
erythrocytes lifespan is about 120 days
hemoglobin degraded to AAs and heme
heme not recycled, degraded (converted to bilirubin)
bilirubin trnasported to liver bound to albumin
97
bilirubin
toxic pigment derived from heme
majorly from erythrocyte turnover
2 enzymatic steps for heme to bilirubin
binds albumin to insoluble H2O
taken up by hepatocytes for clearance from plasma
98
heme to bilirubin
in macrophages of reticuloendothelial system for aged RBCs
leads to color changes in bruises
99
jaundice
high serum bilirubin
caused by excess bilirubin production, decreased bilirubin excretion
100
hepatic bilirubin clearance
specific transporter in cellular uptake
enzyme conjugates to mono/do glucuronide forms
conjugated bilirubin trnasported into bile caniculus and excreted in bile
101
bilirubin measurement
indirect (unconjugated) and direct (conjugated)
conjugated hyperbilirubinemia detected by urine dipstick
102
bilirubin conjugation
single enzyme adds glucuronic acid
produces diconjugated form
normally all conjugated excreted
can cross glomerulus
103
glucuronidiation
adding glucuronic acid to increase solubility and excretion
1 of primary paths of detox of small molecules
2 gene families UGT1 and UGT2 (UGT1A1 only bilirubin conjugated form)
104
UGT1 mutations
toxicity and body burden of bilirubin primary problem
gringler najjar - specific for bilirubin or number of substrates (type 1 no UGT1A1 activity or type 2 low UGT1A1 activity)
gilberts generally asymptomatic - mild unconjugated bilirubin, issues in UGT1A1 promoter
105
drugs affect UGT1A1
competitive and noncompetitive inhibition
HIV protease inhibitors
antineoplastic agents
106
Dubbin Johns Syndrome
conjugated hyperbilirubinemia
defect transport from hepatocyte to bile canniculus (mutations in cMOAT/MRP2)
107
rotors syndrome
high conjugated bilirubinemia
urinary coroporphyrin excretion abdnormal
genetic deficit
108
urea cycle in FED state
dietary protein broken into AAs and delived to liver
AA stripped of nitrogen (used to synthesize nitrogen containing molecules)
109
urea cycle in FASTED state
AAs released from smooth muscle protein
AA stripped of nitrogen in liver
110
AA metabolism
1. amino stripped from AA to glutamate and alpha ketoacid
2. glutamate has 2 fates
-generate ammonia through oxidative deamination (GDH)
-generate aspartate from OAA through transamination
3. urea generated from CO2, ammonia, aspartate amino group
111
1st reaction
remove amino group
aminotransaminases remove amino from 1 AA to another alpha keto acid (alpha keto glutarate and glutamate most common pair)
reversible, uses pyroxidal pyrophosphate (vit B6)
used in synthesis and degradation AAs
112
AA nitrogen released as ammonia by
deamination - removal of amine group NH3
deamidation - removal of amide group CONH2
at physiological pH NH3 changes to NH4
113
glutamate collects nitrogen from AAs, N is then
released as NH4 via GDH activity and enters urea cycle OR
transferred from OAA to aspartate which enters urea cycle
leftover alpha ketoglutarate metabolized in TCA cycle or build other AAs
114
glutamate dehydrogenase (GDH)
oxidative deamination
freely reversible
deaminates glutamate to NH4 and alpha ketoglutarate
115
urea
major nitrogen excretory product
116
urea cycle
major disposal form of nitrogen from AAs
1 nitrogen from NH4 by GDH
1 nitrogen from aspartate
carbonyl from CO2
produced in liver, transported to kidneys
117
urea synthesis
first 2vreaction in mitochondria
1. NH4 to carbamoyl phosphate (by carbamoyl phosphate synthase 1 which requires N acetyl glutamate
2. ornithine and carbamoyl phosphate to citrulline (by arnithine transcarbamoylase (OTC)
3. aspartate and citrulline to arginosuccinate (by argininosuccinate synthase)
4. argininosuccinate to arginine and fumarate (by argininosuccinate lyase)
5. arginine to urea (by arginase which is only present in liver)
-ornithine transported back to mitochondria
-fumarate hydrated to malate for TCA cycle and gluconeogenesis
118
regulation
high ammonia stimulates urea formation "feed forward"
high protein diet and fasting increase urea formation and induce urea cycle enzymes
formation of N acetylglutamate - a positive allosteric effector of carbamoyl phosphate synthase 1
119
defects in urea cycle
carbamoylphosphate synthase 1 deficiency (highest mutation rate)
ornithine transcarbamoylase (most common X linked)
120
metabolism of ammonia
blood ammonia must be kept low
sources - AA breakdown, glutamine to glutamate, bacterial enzymes in intestines, purine and pyrimidine metabolism
121
hyperammonemia
high leads to tremors, slurred speech
very high leads to coma and death
1. acquired by alcoholism, hepatitis, biliary obstruction
2. hereditary from genetic deficiencies in enzymes
decreased alphaketoglutarate leads to decreased TCA cycle in brain
122
nucleotide function
produce DNA and RNA
energy storage and transfer
second messengers
activated compounds for synthesis
methyl transfers
enzyme regulation at allosteric sites
123
nucleotides in diet
as DNA, RNA, nucleotides, derivatives
pancreatic DNAse, RNAse, degrade nucleotides/sides
absorbed by intestinal epithelium (most used there)
synthesized or salvaged to maintain levels in tissues
124
synthesis of nucleotides
made in most tissues, liver is major site, brain makes a large amount, transported to RBCs, body must make or recycle
125
purine materials
1 gglycine, 2 nitrogen from glutamines, 2 C from formyl FH4, N from aspartate, C from CO2
ribose 5P to PRPP by PRPP synthase - regulated
PRPP gains glutamine and
gets NH3 added by glutamine phosphoribosylamidotransferase - commited step
formyl C added, another glutamine NH3 added, close ring, add CO2, add aspartate NH3, add formyl C and get IMP (base hypoxanthine)
GDP/ADP inhibit PRPP synthase
GMP/AMP inhibit 1st specific steps
126
salvage of purines
recycling decreases the need for synthesis (need lots of ATP)
free bases can become nucleotides/sides
can convert to other bases through deamination
127
purine nucleoside phosphorylase
removes base from GMP or IMP by phosphorolysis
base degraded and recycled
crucial for immune system
T cells more effected than B cells
128
adenosine deaminase
converts adenosine to inosine
deficiency is severe combined immunodefeciency disease
129
IMP to GMP
oxidized with H2O and NAD
use ATP to add glutamine NH3
130
IMP to AMP
use GTP to add aspartate
remove fumarate
131
returning bases
phosphoribosl transferases add bases to PRPP
APRT for adenine
HGPRT for hypoxanthine and guanine, X linked, mutated in Lesch Nyahn Syndrome (bases degraded and increase uric acid production)
132
pyrimidine synthesis
aspartate bulk, the rest from carbamoyl phosphate
glutamine, CO2 and 2 ATP to carbamoyl phosphate
add aspartate, close ring, modify side chains
ortic acid added to PRPP to develop UMP to UTP
UTP reduced to dUDP then methylated to dTMP
OR
UTP aminated to CTP
133
enzymes in pyrimidine synthesis, 2 rxns
CPS 2, aspartate transcarbamoylase, dihydroorotase all on (CAD) to make orotate
oroate phosphoribosyl transferase and orotidyl acid decarboxylase (UMP synthase) make UMP
134
orotic aciduria
2 steps blocked , 1 protein for both
cannot add ribose to orotic acid made by 1st protein which increases orotic acid in urine
uridine can be given as therapy
135
salvage of pyrimiines
free bases converted to nucleosides
pyrimidine nucleoside phosphorylase uses ribose 1 phosphate (preferred rxn is synthesis)
136
ribonucleotide reductase
converts ribonucleotide diphosphates to deoxyribonucleotide diphosphates
regenerated using NADPH
complex regulation
137
purine degradation
nucleotide to nucleoside to guanine to xanthine to urate (excreted in urine)
138
gout
excess uric acid
allopurinol inhibits
xanthine oxidase deficient
139
pyrimidine degradation
products all soluble
easily excreted
140
adding single carbon groups
tetrahydrofolate, vitamin B12, S-adenosylmothionine
synthetic and conversion reactions
folate and B12 required for functioning
141
flow of 1 carbon subunits
source is AAs or single C compounds
transferred to folate, reduced/oxidized to other forms
added to variety of products
142
folate forms
basic - pteridine ring, several glutamates
extraglutamates removed in intestines, mono form absorbed
2NADPH and DHFR lead to di/tetrahydro forms
FH4 active form in transfers
143
FH4 conversion
formate added to N10 for formyl
methenyl bridge between N10 and N5 then reduced to methelyne form by NADPH
reduced by NADH to N5 methyl
methelyne form used for dTMP synthesis
methyl regenerates SAM for reactions
formyl for purine synthesis
144
folate to difolate by
dihydrofolate dehydrogenase
145
methylene/methyl/formyl forms to tetra folate by
homocysteine methyl transferase, which needs B12
146
formyl to purines for what
DNA synthesis and cell division
147
vitamin B12
corrin ring
cobalt in center
only used in 2 reactions
1. methyl form to convert homocysteine to methionine
2. adenosyl form for methylmalonyl CoA to succinyl CoA which allows byproduct ketogenic AAs and odd chain FA metabolism to enter TCA
148
B12 absorption
usually protein bound
proteins degraded in stomach, bound by R binders from saliva
R binders degraded in intestine, bound by intrinsic factors from stomach
ileal enterocytes take it up and transfer it to transcobalamin 2 for transport in blood
149
gastric issues do what
decrease B12 absorption
150
nucleotides
purine synthesis uses formyl FH4 to prodduce dTMP which uses methylene FH4, vitamin B12 regenerates FH4
low folate or B12 decrease nucleotide production which decreases DNA synthesis and cell division
151
making erythrocytes
very specific program of differentiation
once committed cells divide which decreases size, produce hemoglobin, lose nuclei
decreased DNA synthesis decreases divisions which makes them larger but they still lose nuclei and enter circulation
152
megaloblastic anemia
less erythrocytes
some large or misshapen
153
low folate increases
FIGLU
folate important in pregnancy
154
low B12 increases
methylmalonic acid
neurological symptoms
155
methyl FH4 must donate methyl or it gets stuck
uses B12 to donate homocystein, regenerates methionine/SAM
B12 low means reaction cannot occur and FH4 and homocystein accumulate
156
pharmacological use
sometimes want to slow nucleotide metabolism and DNA synthesis
dTMP made from dUMP using thymidylate synthase and methylene FH4
5FU inhibits enzyme directly
methotrexate inhibits DHFR which blocks regeneration FH4
157
SAM
major methyl donor in many paths
ance it donates SAH cleaved to homosysteine and adenosine
homocysteine methylated to methionine and can become SAM again
requires folate and B12
158
decreased activity in 3 enzymes increase homocysteine
cystathionine synthase inhibited (needs B6)
can use choline to betaine which donates methyl to cysteine instead
159
10 essential amino acids
P - phenylalanine
V - valine
T - tryptophan
T - threonine
I - isoleucine
M - methionine
H - histidine for growth
A - arginine for growth
L - leucine
L - lysine
160
AAs made from glucose
glycolysis - glycine, serine, cysteine, alanine
others - aspartate, asparagine, tyrosine, glutamate, glutamine
161
serine in glycolysis
3 phosphoglycerate makes serine which goes back to glycolysis as 2 phosphoglycerate
162
carbon skeletons of AAs to
glycogenic products (form glucose)
ketogenic products *form ketones)
leuine and lysine solely ketogenic
163
inborn errors of AA metabolism
methionine metabolism - homocysteinuria, cystathioninuria
branched chain metabolism (isoleucine, leucine, valine) - maple syrup urine disease
phenylalanine metabolism - PKU, alcaptonuria, tyrosinemia
ketogenic AA metabolism (lysine, tryptophan) - gluturic acidemia
164
methionine to homocysteine
homocysteine to cysstathionine by cystathionine synthase (inhibited by cystein)
165
degradation methionine
methionine to SAM to SAH to homocysteine to cystathionine to cysteine
errors increases homocysteine bc deficit in cystathionine synthase and cystathionase
166
homocystein highly reactive
atherosclerosis - homocysteine induces peroxidation LDL which deposits it into arterial walls
defective collagen
brain seizures and mental development delayed
167
cystothionuria from
low B12
168
BCAA deaminated by B6 dependent transamination
produces alpha ketoacid
decrease in transamination leads to maple syrup urine disease
TEHN
oxidative decarboxylation using alpha keto dehydrogenase complex which is thiamine dependent (decreases with alcohol use)
169
phenylalanine metabolism
phenylalanine to tyrosine using phenyalanine hydroxylase (PAH)
requires O2 and cofactor BH4
defect leads to PKU
170
alcaptonuria
defect in homogentisate oxidase
homogentisate accumulates and oxidizes
leads to black urine and arthiritic joint pain
171
tyrosinemia
defects in enzyme, accumulates intermediates
type 1 - liver failure and early death
type 2 - eye and skin lesions, neuro problems
frequently observed in premature infants
172
gluturic acidemia
deficient enzym that converts gluturyl CoA to crotaryl CoA
increases gluturic acid in urine
neuro symptoms, skull enlarges
