Metabolic Enzymes Flashcards
1
Q
enolase
A
- pathway/location: glycolysis; cytosol
- general mechanism: dehydration; water removed to convert 2-phosphoglycerate to phosphoenolpyruvate (PEP)
2
Q
aldolase
A
- pathway/location: glycolysis; cytosol
- general mechanism: splits fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate and dihdroxyacetone phosphate
- regulation: aldolase A is inhibited by fructose 1-phosphate, which inhibits both glycolysis and gluconeogenesis
- special notes: types A, B, and C can be used in glycolysis, but ONLY type B can be used in fructose metabolism
3
Q
Acetyl CoA Carboxylase
A
- pathway/location: fatty acid synthesis; cytosol
- general mechanism: carboxylates acetyl CoA to form malonyl CoA. covalently bound to biotin (kind of like pyruvate carboxylase)
RATE-LIMITING; COMMITTED
also a ping-pong mechanism (covalent intermediate) - energy: requires ATP
- regulation: active when dephosphorylated
inactive in dimer form and active when it is formed into polymer filaments
stimulated by citrate
inhibited by malonyl CoA and palmitoyl CoA (long-chain fatty acid)
AMP-dependent protein kinase and phosphatase
indirectly activated by insulin
indirectly inhibited by glucagon and epinephrine
4
Q
lipoprotein lipase
A
- enzyme that breaks down TAGs from chylomicrons (not ones recently digested from diet)
- fatty acids absorbed by neighboring cells or transported to other cells by albumin
- glycerol used by liver to produce glycerol 3-phosphate (glycolysis or gluconeogenesis)
5
Q
coenzyme Q
A
ubiquinone
continues transfer of electrons to complex III
6
Q
big regulatory system for glycogen degradation in muscle
A
- muscle contraction, calcium released from sarcoplasmic reticulum and binds calmodulin, which activates phosphorylase kinase which actives glycogen phosphorylase.
- AMP can also activate glycogen phosphorylase b without calcium under extreme conditions
(insulin inhibits these pathways by activating phosphatase)
7
Q
bile salts
A
detergent-like
- made in the liver and stored in the gallbladder
- increase surface area of lipids for degradation
8
Q
oligomycin and DCCD
A
binds to stack of ATP synthase which prevents the flow of protons and blocks ATP synthase
- because of the buildup of inter membrane protons, additional protons eventually cannot be pumped into the inter membrane space
9
Q
malate dehydrogenase
A
- used when converting pyruvate back to PEP in gluconeogenesis
mitochondrial - oxaloacetate is reduced to malate using NADH and subsequently leaves the mitochondria
cytosolic - malate oxidized again to oxaloacetate using NAD+ - regulation: only goes through this mechanism when cytosolic levels of NADH are okay, which is usually when starting from pyruvate instead of lactate (which produces an NADH
**also oxidizes malate in TCA cycle to produce oxaloacetate and generate one NADH
10
Q
succinyl CoA thiokinase (or synthetase)
A
- pathway/location: TCA cycle; mitochondrial matrix
- general mechanism: cleaves off CoA, moves phosphate to GDP
- energy: generates GTP
- special notes: succinyl CoA is final compound after the degradation of odd-numbered fatty acid chains
11
Q
glycerol kinase
A
rarely happens, but sometimes in liver
- creates glycerol 3-phosphate
12
Q
AntimycinA
A
antibiotic, piscicide
- binds where CoQ docks to complex III preventing transfer
13
Q
heinz bodies
A
- areas where glutathione is not reduced and cannot reduce SH groups in hemoglobin
- things that generate hemolysis:
infection - inflammation from oxidative stress, antibiotics, antipyretics, antimalarials, fava beans
14
Q
where does NADPH for fatty acid synthesis come from?
A
malate dehydrogenase
pentose phosphate pathway
15
Q
glycogen synthase
A
- adds glycosyl units 1-4 glycosidic bonds until there are about 15 units
- adds to nonreducing ends
- regulation: enhanced by presence of glucose 6-phosphate
16
Q
glycosyl (4:6) transferase
A
- pathway/location: glycogenesis; cytosol
- general mechanism: transfers about 8 units to form a branch via a 1-6 glycosidic bond
- diseases: glycogen storage disease - Andersen disease
leads to death
17
Q
synthesis of glycerophospholipids
A
- starting with phosphatidate, phosphate group is activated by CDP-diacylglycerol synthetase.
COMMITTED STEP
- generates CDP-diacylglycerol (good leaving group in CMP) - leaving group can be replaced by inositol or by glycerol (or really any other alcohol
CDP-activated alcohol
added to diacylglycerol
18
Q
PLA2
A
cleaves acyl chain from carbon 2
19
Q
glycogen initiator synthase
A
- begins adding glucosyl residues to glycogenin (tyrosine residue)
20
Q
triacylglycerol synthetase complex
A
- regenerates TAG
- includes acyl-CoA synthetase, acyl-CoA acyltransferase, monoacylglycerol acyltransferase (MGAT), diacylglyderal acyltransferase (DGAT)
21
Q
PLA1
A
cleaves acyl chain from carbon 1
22
Q
transaldolase
A
moves 3 carbons to produce different sugars
23
Q
alternate mechanism for metabolizing monosaccharides
A
- convert to pylol (sugar alcohol) by reducing an aldehyde group and producing an additional hydroxyl group
- used a lot in tissues that utilize fructose as major energy source
- sorbitol is not permeable through membrane, so in hyperglycemia it builds up in lens and nerve cells. this causes water to rush into the cell due to osmotic effects
- cases cataracts, peripheral neuropathy, microvascular damage
24
Q
complex III (cytochrome b/c1)
A
transfers electrons to cytochrome c and pumps a proton out
- cytochrome complexes have iron atoms that alternate between oxidized (3+ ferric) and reduced (2+ ferrous)
25
phosphoglucomutase
- pathway/location: cytoplasm?
| - general mechanism: interconverts between glucose 6-phosphate and glucose 1-phosphate (for use in glycogen synthesis)
26
triose phosphate isomerase
- pathway/location: glycolysis; cytosol
- general mechanism: interconverts between glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (which can be used in fatty acid synthesis)
27
GALT - galactose 1-phosphate uridyltransferase
adds UDP to galactose from UDP-glucose
- disease: classic galactosemia
can cause severe mental retardation and cataracts due to buildup of galactose 1-phosphate
remove galactose from diet
28
sphingolipids
made from sphingosine, 1 acyl chain, and a phosphate/choline head
29
DHAP reductase
DHAP to glycerol 3-phosphate
30
synthesis of arachidonic acid
comes from linoleic acid (double bond at 9 and 12)
1. linoleic acid activated by the addition of CoA
2. desaturase introduces an additional double bond at carbon 6
3. chain is elongated in the ER using malonyl CoA (this adds 3 carbons)
4. a desaturase introduces another double bond at carbon 5 (because the carbons were all pushed down
* finally unsaturated at 5, 8, 11, and 14
31
phosphopentose epimerase
interconverts between ribulose 5-phosphate and xylulose 5-phosphate
32
nucleoside biphosphate kinase
interconverts between GTP and ATP
33
glyceraldehyde 3-phosphate dehydrogenase
- pathway/location: glycolysis; cytosol
- general mechanism: uses an inorganic phosphate and reducing agent to phosphorylate glyceraldehyde 3-phosphate to produce 1,3-bisphosphoglycerate.
- energy: generates NADH
- regulation: Arsenic poisoning
arsenic competes with inorganic phosphate for the enzyme to form a compound that spontaneously hydrolyzes to 3-phosphoglycerate, thereby skipping the generation of ATP that occurs in the next step
34
regenerated substrate of TCA cycle
oxaloacetate because it is regenerated
35
UDP-glucose-pyrophosphorylase
- pathway/location: glycogenesis; cytosol
- general mechanism: combines glucose 1-phosphate and UTP to produce UDP-glucose
- energy: requires input of UTP
36
amylose
found in plants, don't have branching
37
intracellular reducing agents (anti-oxidants)
beta carotene, vitamin E, ascorbate (vitamin C)
38
isocitrate dehydrogenase
- pathway/location: TCA; mitochondrial matrix
- general mechanism: oxidizes and decarboxylates isocitrate
IRREVERSIBLE and rate limiting
- energy: generates NADH
- regulation: activated by ADP and calcium, inhibited by ATP and NADH
- byproducts: releases CO2
39
phosphofructokinase-2
- pathway/location: glycolysis and gluconeogenesis reversal step;cytosol
- general mechanism: regulatory enzyme
bi-functional - kinase (active when dephosphorylated) and phosphatase (active when phosphorylase)
acts on fructose 2,6-bisphosphate and fructose 6-phosphate
- regulation:
phosphorylated by generation of cAMP/activated PKA from high levels of glucagon
dephosphorylated (kind of) by high levels of insulin/low levels of glucagon
40
sorbitol dehydrogenase
oxidizes sorbitol to produce fructose
| - found in liver, ovaries, seminal vesicles
41
alpha-ketoglutarate dehydrogenase complex
- pathway/location: TCA; mitochondrial matrix
- general mechanism: oxidation and decarboxylation of alpha-ketoglutarate. Uses CoA
IRREVERSIBLE
- energy: produces NADH
- regulation: inhibited by products; NADH and succinylcholine CoA
enhanced by calcium (same as pyruvate dehydrogenase complex)
- byproducts: releases CO2
- coenzymes: NAD, FAD, TPP, lipoic acid, CoA
42
importance of galactose
structural carbohydrate component
43
serine palmitoyltransferase
first enzyme (committing) in the synthesis of sphingolipids
- outside surface of ER
- reaction between palmitoyl CoA and serine
- releases CO2 and generates NADP+ and FADH2
after this, the ketone is reduced to a hydroxyl group (dihydro sphingosine)
acyl chain is added to the nitrogen creating a dihydroceramide
then this is oxidized to generate a double bond (ceramide)
- generates FADH2
finally different groups are added to the free hydroxyl group on the ceramide
*ceramide can form into these super cool channels in the mitochondrial membrane, which allows for the release of cytochrome c and starts the apoptotic cascade
44
mixed miscelles
- formed by digested fats in the intestinal lumen after they have been reformed
- packaged by apolipoproteins (B48 and B100) into chylomicrons making them more hydrophilic. phospholipids also present in the outer layer
- apolipoproteins stabilize structure, make them more soluble, and prevent them from sticking together
- driven by the hydrophobic effect
45
Mannose metabolism
1. hexokinase: mannose 6-phosphate
| 2. phosphomannose isomerase: fructose 6-phosphate
46
energy in fatty acid synthesis for fatty acid with 16 carbons
- 8 acetyl CoA
- 14 NADPH
- 7 ATP
47
complex I (NADH dehydrogenase)
first proton pump (only NADH goes through this complex)
48
shuttle mechanisms
- glycerophosphate shuttle
glycerophosphate dehydrogenase in the cytosol reduces dihydroxyacetone phosphate to glycerol 3-phosphate generating NAD+
then reoxidized by mitochondrial glycerophosphate dehydrogenase passing electrons to create FADH2, which goes through complex II and then ubiquinone
49
glutathione peroxidase
reduces hydrogen peroxide to water (hydrogen peroxide produced by partial reduction of molecular oxygen)
50
glucose 6-phosphatase
- pathway/location: gluconeogenesis; cytoplasm, but only found in liver
- general mechanism: removes phosphate from glucose 6-phosphate to generate glucose
first, glucose must be transported to the liver, which occurs via a shuttle mechanism
51
phosphatidylinositol and signalling
- phospholipase A2 releases arachidonic acid (precursor for prostaglandin)
mostly create extracellular eicosanoid signaling molecules (short term)
- phospholipase C cleaves the inositol group and leaves a DAG
inositol triphosphate releases calcium
DAG can also activate proteins, starting a phosphorylation cascade
52
lactose synthesis
beta-galactose and glucose
- beta-D-galactosyltransferase in many tissues because it is also involved in biosynthesis of a component of N-linked glycoproteins dimerizes with alpha-lactalbumin, which is only found in mammary glands (stimulated by prolactin) to form lactose synthase
- synthesized in the golgi by UDP-galactose:glucose galactosyltransferase (aka lactose synthase)
- transfers galactose from UDP-galactose to glucose
53
lactate dehydrogenase
pathway/location: conversion of pyruvate to lactate; cytosol
general mechanism: interconverts between pyruvate and lactate using NADH/NAD+
energy: conversion to lactate uses NADH and produces NAD+
54
pancreatic lipase
uses water to release 2 fatty acid chains from triacylglycerol (from carbons 1 and 3)
- leaves 2 - monoacylglycerol
- has catalytic triad made of serine, histidine, and aspartic acid
55
fatty acid synthase
- pathway/location: fatty acid synthesis; near the ER
- general mechanism: 7 different catalytic activities
MAT transfers either acetyl CoA or malonyl CoA to ACP site, which then transfers it to a cysteine residues in the ketoacyl synthase site (in the middle)
1. malonyl transferase transfers acetyl CoA to ACP, which transfers it to ketoacyl synthase site.
2. MAT transfers malonyl CoA to ACP, which transfers it to ketoacyl synthase site (condensation)
- releases CO2
*can also use propionyl CoA to form odd-chain fatty acids
*length stops at 16 carbons
*active site in dimer interface
2. ketoacyl-ACP reductase uses NADPH to reduce the second carbonyl to a hydroxyl group
3. a dehydratase removes a water, creation a double bond
4. double bond is reduced again by a enoyl-ACP reductase
5. when synthesis is complete (after multiple rounds), palmitoyl thioesterase removes the fatty acid from the enzyme
- special notes:
ACP domain has a phosphopantetheine prosthetic group
condensation cannot occur between acetyl CoA and another acetyl CoA
*additional carbons can be added by other enzymes
*up to 24 carbons fatty acid chains can be created
*mixed oxidases using NADPH as a cofactor can be used to desaturate enzymes (but only up to carbon 9
56
special tissues/cells
- RBCs, kidney, testes, lens, cornea, actively contracting muscle are likely to have high levels of lactate because they primarily use anaerobic glycolysis
- this is probably due to reduced access to glycolysis
57
aconitase
- converts citrate into isocitrate via isomerase reaction.
- reversible
- regulation:
fluoroacetate (found in rat poison) inhibits it
58
glucose 6-phosphate dehydrogenase
oxidizes glucose 6-phosphate to produce 6-phosphogluconate and NADH
- uses H2O
IRREVERSIBLE
- disease: most common enzyme disease in humans
hemolytic anemia because can't produce NADPH to detoxify free radicals
59
glucose 6-phosphate translocase
- pathway/location: gluconeogenesis; ER membrane
- general mechanism: transfers glucose 6-phosphate into the liver
- special notes: additional transporters are used to transport glucose back out of the ER lumen then GLUT-2 back into the bloodstream
60
where does beta oxidation of fatty acids occur?
mitochondrial matrix
61
phosphoglucose isomerase
- pathway/location: glycolysis; cytosol
| - general mechanism: isomerizes glucose 6-phosphate to produce fructose 6-phosphate
62
odd-chain fatty acids
- ends with propionyl CoA (3 carbons)
1. carboxylation (similar mechanism to the one that generates malonyl CoA)
- D-methylmalonyl CoA
2. changed to L-methylmalonyl CoA by cobalamin (mutase)
3. then changed to succinyl CoA by a radical mechanism
63
phosphoglycerate mutase
- pathway/location: glycolysis; cytosol
| - general mechanism: transfers phosphate group from the 3 carbon to the 2 carbon to produce 2-phosphoglycerate
64
glycogen phosphorylase
- pathway/location: glycogenolysis; cytosol
- general mechanism: breaks the 1-4 glycosidic bonds cleaving glucose 1-phosphate until there are only 4 units left (limit dextrin).
- Requires pyroxidal phosphate covalently bound
- regulation:
in liver: inhibited by ATP, glucose 6-phosphate, and glucose
in muscle: inhibited by ATP, glucose 6-phosphate
enhanced by calcium, AMP
- McArdle Syndrome (muscle enzyme)
- Hers Syndrome (liver enzyme)
65
CN-, CO, sodium azide
prevents transfer of electrons to oxygen at complex IV
66
High Fructose Corn Syrup
55% fructose 45% glucose
- fructose is 30% sweeter by weight than glucose, and it's cheaper than cane sugar
- glucose isomerase converts some of the glucose to fructose
- big deal because entry of fructose into cells is insulin-independent
67
ribulose 5-phosphate isomerase
interconverts between ribulose 5-phosphate and ribose 5-phosphate
68
acyl glycerol 3-phosphate acyltransferase
transfers acyl to glycerol 3-phosphate that already has an acyl group added
69
TAG
- storage form
- carbon 1 is usually saturated, carbon 2 is usually desaturated, and carbon 3 can be either
- cannot be absorbed directly from food
- broken down from chylomicrons primarily in the capillaries of skeletal muscle and adipose tissue
After fatty acid synthesis
- fatty acids have to be activated by the addition of CoA
70
complex IV (cytochrome oxidase)
transfers electrons to molecular oxygen generated
water
- heme interacts with oxygen in proximity to bound copper atoms to generate water. also uses a proton
71
amylo (1:6) glucosidase
- pathway/location: glycogenolysis; cytosol
- general mechanism: releases free glucose unit
- disease: cori disease - fasting hypoglycemia; deformed glycogen
72
potential products of pentose phosphate pathway
NADPH, nucleotides, nucleic acids
73
cori cycle
- in muscle - lactate produced in muscle is transported to liver where it is converted to glucose via gluconeogenesis
74
LHON
leber hereditary optic neuropathy
- blindness from problems transferring electrons to ubiquinone
- damages retinal ganglion cells and their axons
75
glycerol 3-phosphate acyl transferase
transfers acyl to glycerol 3-phosphate
76
complex II (succinate dehydrogenase)
doesn't actually pump protons
| first stop for FADH2
77
pyruvate dehydrogenase complex
- converts pyruvate to acetyl CoA in the mitochondrial matrix
- 3 enzymes: pyruvate decarboxylase, dihydrolipoyl acyltransferase, dihydrolipoyl dehydrogenase
- 5 coenzymes: NAD, FAD, CoA (w/ pantothenic acid), TPP, lipoic acid
- 5 rxns
- ultimately generates CO2 and NADH (for each molecule of pyruvate)
- regulation: active when dephosphorylated
phosphatase is activated by calcium, which activates enzyme
kinase is activated by ATP, Acetyl CoA, and NADH, and inactivated by AMP, CoA, and pyruvate
product inhibition, so inhibited by acetyl CoA and NADH
also inhibited by arsenic, which forms a stable complex with lipoic acid, preventing it from serving as a coenzyme
- disease: deficiency results in fetal lactic acidosis because pyruvate cannot enter the TCA cycle and is instead converted to lactate
primarily affects the brain and can lead to death
78
cholesterol esterase
uses water to release fatty acid from cholesterol ester
79
6-phosphogluconate dehydrogenase
oxidizes 6-phosphogluconate to ribulose 5-phoshpate generating NADPH and CO2
IRREVERSIBLE
80
acyl CoA cholesterol acyltransferase
- cholesterol is re-esterified with a fatty acyl CoA
81
ATP-citrate lyase
- pathway/location: generates Acetyl CoA; cytosol
- general mechanism: uses ATP and CoA to break citrate into oxaloacetate and Acetyl CoA in the cytosol
- energy: requires ATP
- regulation: unregulated by insulin indirectly via phosphorylation cascade
- cofactors: CoA, Mg
- special notes: links energy metabolism from carbohydrates to fatty acid synthesis
DETAILED MECHANISM IN SLIDES and notes
82
stoichiometric substrate of TCA cycle
Acetyl CoA because it is consumed
83
lysophospholipid
phospholipid that is missing one of its acyl chains
84
path of fructose metabolism that differs from glycolysis
1. fructose phosphorylated to fructose 1-phosphate by fructokinase
2. fructose 1-phosphate cleaved to form glyceraldehyde
3. glyceraldehyde is phosphorylated by glyceraldehyde 3-phosphate by glyceraldehyde kinase
*happens more quickly than glycolysis because it skips the rate-limiting step
- disease: aldolase b issues
hereditary fructose intolerance: deadly due to hepatic failure
intracellular trapping of fructose 6-phosphate
have to remove fructose and sucrose from the diet
85
cahill cycle
- in muscle - alanine is created from nitrogens from broken down amino acids and pyruvate
- alanine transported to liver, where it is broken down. Nitrogens are diverted to urea cycle and pyruvate is converted to glucose via gluconeogenesis
- requires 4 ATP and 2 GTP
86
glucose 6-phosphatase
- pathway/location: gluconeogenesis; liver lumen of ER
- general mechanism: removes phosphate of glucose 6-phosphate to regenerate glucose
- coenzymes: utilizes a molecule of H2O
- diseases: von gierke disease (deficiency of either the phosphatase or the translocase)
severe fasting hypoglycemia
some issues may be caused by antimalarials, etc
- special notes: not present in muscle, which is why muscle cannot produce free glucose
87
amytol/amobarbitol
inhibits ETC between complex I and complex II
| - blocks transfer from FMH2 to FE-S cluster
88
how many ATP consumed when acetyl CoA is transported out of the mitochondria?
2
- one during the formation of citrate (in the creation of oxaloacetate from pyruvate
- one during the creation of acetyl CoA from citrate in the cytosol (ATP-citrate lyase)
89
pyruvate kinase
- pathway/location: glycolysis; cytosol
- general mechanism: transfers phosphate group from PEP to ADP resulting in pyruvate
IRREVERSIBLE
- energy: generates ATP
- regulation:
active when dephosphorylated, which means that it is inactive when glucagon is high, starting the phosphorylation cascade
activated by fructose 1,6-bisphosphate
feed-forward regulation
- diseases: most common form of glycolysis disease
decreased ATP production results in hemolytic anemia
think about multiple ways that the kinetic activity of the enzyme might be lowered
90
ATP equivalents for different energy carriers
NADH - 3 ATP (unless coming from glycolysis)
| FADH2 - 2 ATP
91
glutathione reductase
reduces glutathione so that it can be used to reduce reactive oxygen species
92
Fatty acyl CoA synthetase
- uses ATP to activate fatty acid chains by the addition of CoA
- creates a good leaving group (CoA)
- located on outer mitochondrial membrane
- adds fatty acids to glycerol or glycerol phosphate
also a ping pong mechanism
1. forms an acyl adenylate reaction of fatty acid with ATP
2. CoA attacks acyl adenylate to form acyl CoA and AMP
93
phosphoglycerate kinase
- pathway/location: glycolysis; cytosol
- general mechanism: transfers a phosphate group from 1,3-BPG to ADP resulting in 3-phosphoglycerate
- energy: energy generation stage; produces ATP
94
what is NADPH used for?
bioreductive pathways
- fatty acids reduced in liver and mammary glands
- steroids reduced in adrenal cortex, ovaries, testes
- erythrocytes - keep glutathione reduced
95
phosphofructokinase-1
- pathway/location: glycolysis; cytosol
IRREVERSIBLE
RATE-LIMITING
- general mechanism: phosphorylates fructose 6-phosphate to produce fructose 1,6-bisphosphate
- energy: energy investment phase; requires ATP
- regulation:
enhanced by fructose 2,6-bisphosphate, AMP
inhibited by ATP, citrate
96
CPEO
chronic progressive external opthalmoplegia
- slow progressive paralysis of EOM from large deletions in mitochondrial DNA
- more severe is kearns-sayrer syndrome
97
rotenone
insecticide, piscicide
| - blocks transfer from Fe-S to Q
98
advantages of branching
- increased solubility
| - additional places for addition of glycosyl units
99
phosphatidate
glycerol with 2 fatty acid chains and a phosphate
| - this can either be dephosphorylated to generate a TAG for storage or can be used to create a phospholipid
100
succinate dehydrogenase
- pathway/location: TCA; inner mitochondrial membrane
- general mechanism: oxidizes succinate
- energy: generates FADH2
101
ATP Synthase structure and mechanism
review notes for answer
102
glucokinase
- pathway/location: glycolysis; stored in nucleus when inactive, acts in the nucleus. Found in the liver and pancreatic beta cells.
IRREVERSIBLE
COMMITTING
- general mechanism: also phosphorylates glucose to commit it to metabolism by trapping it in the cell
energy: energy investment phase; requires ATP
- resulting compound: glucose 6-phosphate
- regulation: glucokinase regulatory protein (GKRP). Positive: released from nucleus when glucose levels are high.
Negative: high levels of fructose 6-phosphate cause translocation back to nucleus.
- byproducts: ADP
- diseases:
- special notes:
103
carnitine shuttle
1. charged fatty acid from the cytosol - CoA is replaced by carnitine. (carnitine palmitoyl transferase I - outer mitochondrial membrane)
2. carnitine can cross the inner mitochondrial membrane via a translocase, but is replaced by mitochondrial CoA once in the matrix (carnitine palmitoyl transferase II inner mitochondrial membrane)
* tunnel sequesters the fatty acid
104
fumarase
- pathway/location: TCA; mitochondrial matrix
| - general mechanism: hydrates fumarate using H2O
105
where does oxidative phosphorylation occur
inner mitochondrial membrane
106
glycosphingolipids
made from sphingosine, 1 acyl chain, and mono/oligosaccharides
107
CCT
creates phosphatidyl choline from choline and a DAG using ATP and CTP
108
first step necessary in TCA cycle
pyruvate must be transported into the mitochondrial matrix via a transporter
109
PLD
cleaves acyl chain from carbon 3 WITHOUT the phosphate group
110
citrate synthase
catalyzes reaction between acetyl CoA and oxaloacetate to form citrate using water. releases CoA
IRREVERSIBLE
aldo condensation
111
very long chain fatty acids
peroxisomes break them up into smaller chains
- electrons delivered to water to form H2O2, which is then broken down
- smaller chains moved to mitochondria to go through normal beta oxidation
112
cytochrome c
continues transfer of electrons to complex IV
located in inner mitochondrial membrane
soluble protein
113
50% of enzymes in mitochondrial matrix are there for what purposes?
oxidation of fatty acids
conversion of pyruvate into acetyl CoA
TCA cycle
114
transketolase
moves 2 carbons to produce different sugars
115
where is glycogen stored?
liver, kidney, muscle as granules in cytoplasm
| - glycogen in muscle is ONLY broken down when muscles are exercising
116
galactokinase
phosphorylates galactose to galactose 1-phosphate
| - disease: galactokinase deficiency causes galastosemia and galactosuria
117
generation of 2,3-BPG
- occurs in RBCs
- generated from glyceraldehyde 3-phosphate by a mutate and then hydrolyzed to 3-phosphoglycerate by a phosphatase
- this also skips the ATP generation step around this part of glycolysis
118
glucosyl (4:4) transferase
- pathway/location: glycogenolysis; cytosol
| - general mechanism: transfers glucosyl units from branches to other non-reducing ends.
119
PEP carboxykinase
- location: cytosolic and mitochondrial
- general mechanism: oxaloacetate decarboxylated and phosphorylated to generate PEP.
byproducts: carbon dioxide
120
fructokinase
- primary enzyme that phosphorylates fructose. much higher affinity than hexokinase
- found in liver, kidney, and small intestine
- liver is where most dietary fructose is processed
- disease: essential fructosuria
benign and asymptomatic
121
cardiolipin
- only in the inner mitochondrial membrane
- basically 2 phospholipids connected by a glycerol backbone
- the head group has capacity for additional hydrogen bonding, which stabilizes it.
- it gives a negative charge and makes the membrane less permeable
122
calmodulin system
- cell membrane is impermeable to calcium, and gradient is maintained by calcium pumps.
- 4 calcium ions bind to calmodulin, which goes on to activate calmodulin-dependent enzymes, such as:
- calmodulin-dependent PKs, adenyl cyclase, guanyl cyclase, phosphodiesterase, ATP-dependent calcium pump
123
aldose reductase
reduces glucose to produce sorbitol
also reduces galactose to galactitol
- uses NADPH as reducing agent
- found in lens and retina, peripheral nerves (schwann cells), kidney, placenta, liver, ovaries, seminal vesicles
124
phospholipase
uses water to release 2 fatty acid chains from phospholipids
125
lysosomal alpha-1-4 glucosidase
- small alternative pathway
- hydrolyzes glucosyl units in lysosome
- disease: pompe disease - lysosomal storage disease
not a major pathway, but it's a big deal when this goes wrong. glycogen builds up in lysosomes.
leads to cardiomegaly and heart failure
126
pyruvate carboxylase
- pathway/location: gluconeogenesis; mitochondrial matrix
- general mechanism: biotin is attached to enzyme via lysine residue. biotin is then carboxylated using ATP
regulation: activated by Acetyl CoA
carbon dioxide transferred to pyruvate to generate oxaloacetate
127
fructose bisphosphate phosphatase-1
- pathway/location: gluconeogenesis; cytosol
| - general mechanism: converts fructose 1,6-bisphosphate to fructose 6-phosphate
128
cis unsaturated fatty acids
1. enoyl CoA isomerase moves the double bond over to the right by one position, which forms a double bond
2. 2,4-dienoyl reductase is necessary when there are 2 double bonds
129
where do the precursors of gluconeogenesis come from?
- triacylglycerides
- amino acids
- intermediates of glycolysis and the TCA cycle
- lactate
130
alternate fates of pyruvate
ethanol
oxaloacetate
lactate
acetyl CoA
131
where is fructose found as a free monosaccharide
fruit, honey, HFCS
132
possible clinical outcomes of lactic acidosis
hemorrhage
MI
shock
PE
133
when does gluconeogenesis occur?
- when glycogen stores in the liver have been depleted
| - tightly regulated because it is so energetically costly
134
beta oxidation of fatty acids
1. double bond introduced through oxidation
- acyl CoA dehydrogenase (generates FADH2)
2. hydroxyl group formed
- enoyl CoA hydratase
3. hydroxyl group oxidized to ketone
- dehydrogenase (generates NADH)
4. separated to produce acetyl CoA (12 ATP)
- thiolase
135
cytochrome P450 monooxygenase superfamily
- enzymes that process xenobiotics
- may activate/deactivate medications
- uses NADPH to split oxygen to add hydroxyl group to substrate, making them more soluble
- smooth ER of liver
136
PLC
cleaves acyl chain from carbon 3 WITH the phosphate group
137
Possible ways for NADH to be regenerated to NAD+ for use in subsequent glycolytic reactions
oxygen (ETC) or conversion of pyruvate to lactate
138
hexokinase
- pathway/location: glycolysis; cytosol
- general mechanism: phosphorylates glucose, which traps it in the cell and commits it to metabolism.
IRREVERSIBLE
COMMITTING
- resulting compound: glucose 6-phoshpate, fructose 6-phosphate
- energy: energy investment phase; requires ATP
- regulation: inhibited by product - glucose 6-phosphate
- byproducts: ADP
139
ketone bodies
during a fasting state, oxaloacetate is diverted too gluconeogenesis. It cannot be used in the TCA cycle, which means that acetyl CoA accumulates
- acetyl CoA is condensed to form acetoacetyl CoA and then to acetoacetate
- acetoacetate is transported to peripheral tissues and converted back to 2 acetyl CoAs
- the acetoacetate can also be converted to ketone bodies (D-3-hydroxybutyrate, acetone)
140
essential fatty acids
```
linoleic acid (9 and 12 cis bonds)
linolenic acid (9, 12, 15 cis bonds)
*humans cannot desaturate past 9 carbons
```
141
glycerophospholipids
made from glycerol, 2 acyl chains, and phosphate and alcohol
