Week 1 Flashcards
Oxidation-Reduction class of enzyme
Oxidoreductases
e.g.. Lactate Dehydrogenase
Group transfer class of enzyme
Transferases
additional or removal of groups to form double bonds
Hydrolases
Isomerization (intermolecular group transfer) class of enzyme
Isomerases
Enzymes that act with Ligation of two substrates at the expense of ATP hydrolysis
Lipases
Enzyme with its cofactor.
Holoenzyme
protein portion of the holoenzyme.
Apoenzyme
tightly bound coenzyme that does not dissociate
Prosthetic group
What do enzymes do to help a reaction move forward?
They Lower the energy of activation, and create favorable orientation of the substrates to react to form product.
Rate of reaction is directly proportional to [E] at all [S]. E.g. If [E] halved, Vo reduced to one half of original.
Michaelis-Menten Kinetics
What is Km?
reflects the affinity of E for S.
Equivalent to [s] at with Vo is Equal to 1/2 Vmax
________is a response of an enzyme to an effector molecule that results in an increase or decrease in its activity
Allosterism
Inhibition reversed by increasing [S]. At a sufficiently high [S] the reaction velocity reaches the Vmax observed in absence of Inhibitor.
Competitive Inhibitors
increases the apparent Km-max for a given S. More substrate is needed to achieve 1/2 V
Vmax itself is not effected.
Competitive Inhibitors
2-12 monosaccharides
Oligosaccharides
Differ only
in configuration
around a single
carbon atom
Epimers
is a cyclic saccharide and an epimer that differs in configuration, specifically at the hemiacetal/acetal carbon, also called the anomeric carbon.
Anomers
e.g.. alpha and beta Glucose
An __________ bond is formed when the OH group attached to an anomeric carbon condenses with a group on another monosaccharide
O-glycosidic
Beta Lactose Bonds
Galactose B1-4 Glucose
Sucrose bonds
Glucose a1-2 Fructose
Maltose bonds
Glucose a1-4 Glucose
Glycosidic bonds (glycogen)
α-1,4- and α-1,6-(branch)
Amylose Bonds
a 1-4
______is the helical form of starch comprised only of _____linkages, and______ has a structure like glycogen except that the branched_____ linkages are present on only about one in 30 monomers.
amylose, alpha-1,4
amylopectin, alpha-1,6
Brush Border Enzymes
- Sucrase
- Lactase
- Maltase
- Isomaltase
- a-maltase (breaks a,1-6)
Passage of undigested carbohydrate into large intestine, results in:
- Osmotic diarrhea.
- Bacterial fermentation of carbohydrate to 2 and 3 C fragments plus CO2 and H2
gas
Congenital Sucrose Intolerance.
Sucrase-Isomaltase Deficiency is also known as SI Deficiency, Disaccharide Intolerance I
10% of Greenland’s Eskimos deficient
_________ is able to attach to the tooth surface and form a biofilm.
The______ slime can be depolymerized to glucose resulting in production of lactic acid
S. mutans
dextran
GLUT__ (high affinity) brain and rbc
1
GLUT__ liver, kidney, intestine and β cells
2
GLUT __nearly all cells
3
GLUT__ insulin- dependent isoform present in muscle and adipose
4
GLUT __ small intestine on arterial side of the epithelial cell.
5
Active transport areas for Glucose.
Epithelia of small intestine
Renal Tubules
Choroid Plexus
Insulin Insensitive tissues
- Epithelia of small intestine
- Renal Tubules
- Choroid Plexus
- Erythrocytes
- lens of eye
- liver
- Brain
In the Lumen of the small intestine cotransport of glucose is mediated by a Na+ glucose symporter ______
SGLT1
Glucose Newly Arrived in the Cell is Phosphorylated by
Hexokinase
Products of Glycolysis for one glucose molecule
2 ATP(net)
2 NADH
2 Pyruvate
Under anaerobic conditions pyruvate is reduced to lactate with the concomitant oxidation of_____ to ______ to allow for the continuation of glycolysis
NADH
NAD+
Instead of Hexokinase Glucokinase is found in
Liver and β cells
Allosterically inhibited by Glucose 6 phosphate.
Hexokinase
adds Pi to Phosphoenolpyruvate (PEP) to make Pyruvate
Pyruvate Kinase
Most significant regulator of PFKI is _____________________ which strongly activates PFK1
fructose 2, 6 bisphosphate
[Fructose 2, 6 bisphosphate] in liver declines with [_______], slowing glycolysis and stimulating liver glucose synthesis.
Glucagon
Pyruvate passes through the outer mitochondrial membrane via porins. _______, a protein embedded in inner mitochondrial membrane specifically transports pyruvate into the matrix in______ with OH-
Pyruvate translocase
antiport
Prosthetic groups of The Pyruvate Dehydrogenase Complex
TPP (thiamine diphosphate, Vitamin B1)
Lipoamide
FAD (vitamin B2)
The yield for one Acetyl group going through the CAC.
1 GTP
1 FADH2
3 NADH
1 CO2
n total a theoretical value of ____ATPs are possible from the oxidation of glucose
32
Rate limiting steps of the Citric Acid Cycle
- Citrate Synthase reaction
- Isocitrate Dehydrogenase
reaction - α-Ketoglutarate
Dehydrogenase reaction
PDHC is regulated by multiple allosteric interactions and by covalent modification.
What Allosteric inhibits PDHC?
Products of the CAC, as well as long chain fatty acids.
(ATP, acetyl CoA, NADH
and GTP)
PDHC is regulated by multiple allosteric interactions and by covalent modification.
What Allosteric up regulates PDHC?
Precursors to Acetyl Coa, and the high energy products from PDHC
AMP, CoA, NAD+ and Ca2+
In Covalent Regulation of PDHC
PDHC ACTIVE
when___________
dephosphorylated
inCovalent Regulation of PDHC
PDHC INACTIVE
when____________
phosphorylated
The important precursor molecules of glucose are.
lactate pyruvate glycerol and most amino acids.
Biotin is B vitamin____.
7
Conversion of Pyruvate into PEP while in the mitochondrial matrix In GNG is facilitated by the enzyme_________.
pyruvate carboxylase
Oxaloacetate is Reduced to Malate before bing transported out of the mitochondria into the cytosol during GNG. Oxaloacetate is then simultaneously decarboxylated and phosphorylated to form PEP at the expense of a GTP in the cytosol. This reaction is catalyzed by ______________.
PEP carboxykinase
The conversion of lactate to pyruvate in the liver cytosol yields NADH (a reaction favored by the low NADH/NAD+ ratio in the cytosol of liver cells). This is a reaction catalyzed by ____________.
lactate dehydrogenase
In GNG Fructose 6-phosphate is formed by hydrolysis of the phosphate group at C1, in a exergonic reaction catalyzed by ___________.
fructose 1,6- bisphosphatase.
in GNG Glucose 6-phosphate is converted into Glucose by the enzyme.
Glucose 6-phosphatase
Glycerol results from triacylglycerol hydrolysis in adipose tissue. In liver and kidney, glycerol is converted to glycerol 3- phosphate by ____________
glycerol kinase
__high-energy phosphate bonds (__ x ATP and __ x GTP) are used to synthesize glucose from
pyruvate in gluconeogenesis - whereas only two molecules of ATP are generated in glycolysis in the conversion of glucose into pyruvate. Additionally, __ molecules of NADH are required.
6 ATP + GTP
4 ATP
2 GTP
+ 2 NADH
In a resting individual after a meal, liver usually contains ___% of its wet weight as glycogen and muscle about ___%.
4-7
1
Glycogen is degraded by the removal of a terminal glucose residue from the nonreducing end of a glycogen chain by the action of ______________
Further degradation occurs with the action of a debranching enzyme, __________________ with________ activity.
glycogen phosphorylase
oligo (α1-6) to (α1-4) glucantransferase
glucosidase
Glycogen Synthesis Steps
1) Glucose __ phosphate is converted to glucose __ phosphate.
2) Glucose__ phosphate and___ form UDP- glucose and pyrophosphate in a reaction catalyzed by ______________________.
3) The pyrophosphate formed is rapidly hydrolyzed to _____________.
6
1
1
UTP
UDP-glucose pyrophosphorylase
orthophosphate
UDP is displaced by the terminal hydroxyl group of the growing glycogen molecule. This reaction is catalyzed by ___________.
Glycogen synthase
The α(1-6) bonds found at branch points are formed by the glycogen branching enzyme ________________.
Glycosyl (4-6) transferase
Glycogenesis and glycogenolysis are separate metabolic pathways having only one enzyme in common, namely__________________.
Phosphoglucomutase
_____________converts Glycogen phosphorylase b to Glycogen phosphorylase a, the active form.
Phosphorylation
The active form of glycogen synthase, glycogen synthase a is the_______________ form
dephosphorylated
in Muscle:_________ and AMP up-regulates Glycogen phosphorylase activity
Calcium and AMP
Massive Enlargement of the liver, severe hypoglycemia, ketosis, hyperuricemia, hyperlipemia. Effects the Liver and Kidneys
Von Gierke disease
NADH and FADH2
yield in the oxidation of Glucose
CO2: 6
NADH: 10
FAD: 2
ATP: 4
G3P dehydrogenase does what?
exchanges an NADH outside the mitochondrial matrix to yield a FADH2 that may cross the mitochondrial membrane into the matrix
The only ETC complex that does not pump electrons?
Complex II: Succinate dehydrogenase
(NADH-Q oxidoreductase)
AKA
Complex I
NADH-Q oxidoreductase (complex 1) has a tightly bound molecule of _________________ that accepts the 2 H atoms becoming________
flavin mononucleotide (FMN)
FMNH
Iron-Sulfur Clusters are found in all of the ETC complexes except…
Complex IV
Succinate dehydrogenase
AKA
Complex II
Complex II has __ types of prosthetic groups and at least___different proteins.
Electrons pass from succinate to FAD then
through the Fe-S centers to ubiquinone,
reducing it to ubiquinol.
2
4
In Complex II Electrons pass from succinate to____ then through the _____ centers to________, reducing it to_______.
FAD
Fe-S
ubiquinone
ubiquinol
Water in the ETC will need
Cytochrome oxidase Complex IV
O2
4 e-
4 H+
Cytochromes are…
a class of proteins characterized by
presence of iron-containing
heme group.
The cytochrome iron atom is
reversibly converted from its Fe3+
to its Fe2+ form
Fructose absorption finite (______ g per sitting). Excess fructose moves to colon
25-50
Converts Fructose 1-phosphate in the liver to Glyceraldahyde + Dihydroxyphosphate
Fructokinase Aldolase B
In the liver Fructose is phosphorylated to F1P by________, and then to Glyceraldahyde + Dihydroxyphosphate using _______________ bypassing the most important regulation enzyme in glycolysis PFK1 this results in run away glycolysis and a build up of Acetyl CoA.
Fructokinase
Fructokinase Aldolase B
Excessive dietary intake of fructose may lead to decrease in available Pi
Breakdown of residual ADP and AMP resulting in_______ and______
hyperuricemia
gout
Enzyme deficiency:
Fructokinase is ______ and leads to________
Aldolase B is ________, and leads to _______
Benign, Essential Fructosuria
Severe, Hereditary Fructose intolerance
_______________deficiency is an inherited disease characterized by ___________ caused by the inability to detoxify oxidizing agents. Most common disease producing enzyme abnormality in humans, affecting more than 200 million individuals worldwide.
Glucose 6-P Dehydrogenase
hemolytic anemia
Reduced glutathione detoxifies hydrogen peroxide with _____________.
The cell regenerates reduced glutathione with _______________ using NADPH as a source of electrons
Glutathione Peroxidase
Glutathione Reductase
Conversion of mannose to fructose 6 phosphate is mediated by the _____________ enzyme.
Phosphomannos Isomerase
Sucrose To glucose path
Breaks down into Glucose and Fructose Via Sucrase
Transported using
Fructose absorption occurs by facilitated transport through _______ and enter circulation mostly through _________
GLUT 5
GLUT2
PPP The Oxidative Pathway
G6P oxidized to a lactone (a cyclic carboxylic acid) by _________________ 1 NADPH formed
Glucose 6-phosphate dehydrogenase
Which is also the rate limiting step of PPP
___________ Deficiency is the most common enzyme deficiency.
Glucose 6-P Dehydrogenase
Some patients with G6PD Issues will develop a hemolytic anemia if they are treated with:
Antibiotics
Analgesics (painkillers)
Antipyretic (fever reducers)
Glycosaminoglycans (GAGs), covalently linked to protein
Proteoglycans (PG)
The four major classes of GAG disaccharides
Hyaluronan
Chondroitin sulfate
Heparan sulfate
Keratan sulfate
When epithelia are damaged, these complexes are released and diffuse away forming a chemotactic gradient that attracts neutrophils to the site.
Syndecan-1 binding chemokines.
Hunter disease
Enzyme deficiency of Iduronate Sulfatase
Heperan Sulfate and Dematan Sulfate
Accumulate in lysosomes
Synthesized by enzymes on the________
(not post-translationally modified like all
other GAGs).
cell surface
Hyaluronan is also unique among the GAGs
in that it does not contain any_____.
sulfate
Collagen Degradation 3 step process: a) enzyme binding b) Unwinding of triple helix c) Cleavage of collagen peptides
Matrix metalloproteinases (MMPs) and Cathepsins (L and K)
________ is a protease inhibitor. In its absence (1/2500 of US population) neutrophil elastase can degrade elastin leading to emphysema, COPD and liver cirrhosis
α1-antitrypsin
four ECM proteins found in all basal laminae: Laminin Perlecan (Heparan Sulfate PG) Type IV collagen Entactin/Nidogen
Laminin
Perlecan (Heparan Sulfate PG)
Type IV collagen
Entactin/Nidogen