Exam 2 Review Flashcards
two types of functional groups found on the anomeric carbon of straight chain sugars
aldehydes and ketones
glycation
-clinical significance
the process of a protein reaction and combining with a sugar without the presence of a cofactor such as an activated sugar
-Hb can be glycated when diabetics dont take their insulin and take too much sugar and can be used in a test to see if people have been compliant
polysaccharide, glycolipis, and glycoprotein bond formation requirements
- this process is called glycosylation and it differs from glycation in that cofactors are needed to carry out the reaction
- these are in the form of activated sugar nucleotides
glycogen structure
- series of alpha 1,4 linked glucose molecules with alpha 1,6 branches
- the end at which sugars get added is called the nonreducing end
glycosaminoglycans GAGs
- what are they
- most common
long, linear sugars with disaccharide repeats that are negatively charged (sulfates)
- can be free or attached to protein
- chondroitin sulfate is the most common
chondroitin sulfate
bone, cartilage, cornea formation
keratan sulfate
cornea, connective tissue
dermatan sulfate
binds LDL to plasma walls
heparan sulfate
aortic wall, basement membrane
heparin
anticoagulant
hyaluronic acid
cell migration, lubricant, (not covalently attached to protein)
proteoglycans
-provide part of the ground substance for tissue epithelia, bind growth factors/cytokines and provide cushioning in joints
enzymatic glycosylation
-where does it occur
- outside of the cell or oriented outside of the cell except in O-GlcNac
- can be O linked or N linked with a specificity determined by the nucleotide sugar and the substrate
- sugar processing occurs as proteins traffic from the ER through the golgi
what enzymes are involved in I cell disease
- there are multiple!!
- results in the accumulation of many biosynthetic materials
glycoproteins are critical for…
- biological recognition
- mannose-6-P as a lysosomal targeting signal, influenza or helicobacter, leucocyte adhesion deficiency 2
what does lactase insufficiency cause when lactose is consumed
-fluid to rush into the colon causing watery diarrhea and the formation of H2 gas
the different mechanisms in which monosaccharides can enter the cell
simple diffusion, facilitated diffusion, active transport
Glut 4
- type of transport
- found where
- regulation
- difference between glut 2
- facilitated transporter
- important in fat and muscle
- not found in the liver **
- regulated by insulin
- glut 2 is not regulated by insulin
affect of insulin on blood glucose in type 1 diabetics
-blood glucose does not go down nearly as much
insulins action on glucose metabolism
- decreases blood glucose by increasing uptake in muscle and adipose tissue (not in the liver)
- increases glycolysis in the liver, increasing acetyl-CoA formation
- decreases gluconeogenic reactions
- decreases glycogen breakdown and increases synthesis
purpose of forming G6P from Glu
- locks it into the cell so the exterior glucose concentration doesnt pull it back out of the cell
- this is done by hexokinase everywhere and by glucokinase in hepatocytes
- glucokinase in pancreatic beta cells regulates glycolysis and hence insulin secretion (MODY)
glucokinase vs hexokinsae concentrations
- glucokinase is 100 times more concentrated in liver cells than hexokinase is anywhere else in the body
- this makes sure that the liver does not miss any glucose molecules passing through it
4 different things you can do with glucose in a general sense
- glycogen synthesis
- glycolysis
- PPS
- glucuronides
niacin deficiency
- vitamin B3
- dermatitis
- diarrhea
- dementia (pellagra)
thiamine deficiency
- VitB1
- opthalmoplegia
- gait difficulties
- confusion
- beri beri
- wernicke korsakoff
riboflavin
- VB12
- cheilosis and glossitis
lipopoate
-targeted by arsenic (pyruvate and a ketoglutarate dehydrogenase)
ratios of NAD vs NADH and NADPH vs NADP
- NAD+»_space; NADH
- NADPH»_space; NADP
- basically, what the cell wants are NADPH and NAD, these are what are the cell uses as substrates in important reaction
- however, there are reaction within the cell that can convert NADH and NADP back to their original states
- it is an oxidation reduction cycle
regulated enzymes of glycolysis
- hexokinase/glucokinase
- phosphofructokinase 1 (PFK1)
- pyruvate kinase
ATP producing enzymes of glycolysis
- phosphoglycerate kinase (1,3BPG to 3PG)
- pyruvate kinase (PEP to pyruvate)
glycolysis
- where
- yield
- limited by and requires
- deficiencies affect
- regulatory enzymes, reversible?
- what is the most important site of regulation?
- cytoplasm
- 2 ATP per glucose even under anaerobic conditions
- limited by Pi and requires NAD+ (used by G3PDH)
- deficiencies affect mainly RBC’s (anemia, pyruvate kinase) and skeletal muscle (exercise intolerance, PFK1)
- glucokinase, phosphofructokinase, pyruvate kinase (liver vs muscle)
- PFK1 is the most important step in glycolysis
regulation of PFK1
activators: ATP and F2,6BP
- F2,6BP is particularly important because in its absence, F1,6BP could be used for gluconeogenesis (the opposite of glycolysis)
- inhibitors: ATP and citrate
intermediates of glycolysis are used for
- amino acid synthesis
- fats
- nucleic acid
posions that affect glycolysis
- 2 deoxyglucose inhibits hexokinase
- arsenate inhibits G3PDH
- fluoride inhibits enolase
fructose entering the pathway
gets phosphorylated to F1P then aldolase B splits it into DHAP and glyceraldehyde which are both intermediates in glycolysis
fructokinase deficiency vs an aldolase B deficiency
fructokinase: less serious, causes essential fructoseria
- aldolase B: more serious as it causes a build up of F1P which blocks glycogen breakdown and glucose synthesis via sequestering Pi, this is called hereditary fructose intolerance
matabolic diseases of galactose
- galactokinase deficiency causes minor problems
- Gal-1-P-uridyl transferase causes major problems and is called classic galactosemia
what is UDP-Glucoronic acid used for?
- what enzymes does this
- what happens if there is a problem
- conjugated with other molecules such as bilirubin and drugs in order to make them more polar so that they are excreted from the body
- this is done via UGT = UDP-alpha-glucuronyltransferase
- problems cause Gilberts syndrome
alcohol is converted into what and then what?
-what cofactors does this process use? What does that lead to
- acetaldehyde by alcohol dehydrogenase and then acetate by aldehyde dehydrogenase
- acetate can then lead to acidosis or be converted to acetyl CoA
- This process uses 2 NAD and produces 2 NADH
- The increased NADH leads to inhibition of gluconeogenesis and increased triglyceride synthesis by blocking the conversion of FA’s to Acetyl CoA
alternative alcohol pathway, when does this occur
- MEOS (CYTP450) pathway
- uses NADP, creating NADPH
- this is an adaptive pathway and found to be used by alcoholics
- one reason why they can handle more booze
production of NADH from ethanol does what
- inhibits gluconeogenesis
- stimulates fat production
alcoholics are often deficient in what?
- vitamins, particularly thiamine (VB1)
- this causes W-K and beri-beri
PDH is inactivated by
-being phosphorylated by PDH kinase
-what activates PDH kinase and what does this cause
- Acetyl CoA, CO2, NADH (products)
- this causes the inhibitions of the TCA cycle, basically this happens when your body is in an energy surplus
what inactivates PDH kinase and what does this cause
- via inhibiting the kinase:ADP (low energy), Pyruvate, CoASH, NAD+
- By activating the phosphotase: Insulin, Ca++
- This is when your body has low energy or you have just eaten a high carb meal or you have a build up of the substrate for PDH
what macromolecules feed into the TCA cycle
- carbohydrates
- fatty acids
- amino acids
where does the great majority of energy derived from glucose come from?
-TCA cycle
what products do you get from the TCA cycle?
- 3 NADH (isocitrate dehydrogenase, a-KGDH, malate dehydrogenase)
- 2 CO2 (isocitrate DH, a-KGDH)
- FADH2 (succinate DH)
- GTP (succinyl CoA synthetase)
Regulatory enzymes of the TCA, just their names
- citrate synthase
- isocitrate DH
- a-KGDH
- malate dehydrogenase
what regulates citrate synthase
- activator: increased ADP
- inhibitor: NADH, SuccCoA, ATP
what regulates isocitrate DH
- activator: ADP, Ca
- inhibitor: NADH, ATP
what regulates a-KGDH?
- activator: Ca
- inhibitor: NADH, SuccCoA
alcohol is converted into what and then what?
-what cofactors does this process use? What does that lead to
- acetaldehyde by alcohol dehydrogenase and then acetate by aldehyde dehydrogenase
- acetate can then lead to acidosis or be converted to acetyl CoA
- This process uses 2 NAD and produces 2 NADH
- The increased NADH leads to inhibition of gluconeogenesis and increased triglyceride synthesis by blocking the conversion of FA’s to Acetyl CoA
alternative alcohol pathway, when does this occur
- MEOS (CYTP450) pathway
- uses NADP, creating NADPH
- this is an adaptive pathway and found to be used by alcoholics
- one reason why they can handle more booze
production of NADH from ethanol does what
- inhibits gluconeogenesis
- stimulates fat production
alcoholics are often deficient in what?
- vitamins, particularly thiamine (VB1)
- this causes W-K and beri-beri
PDH is inactivated by
-being phosphorylated by PDH kinase
-what activates PDH kinase and what does this cause
- Acetyl CoA, CO2, NADH (products)
- this causes the inhibitions of the TCA cycle, basically this happens when your body is in an energy surplus
what inactivates PDH kinase and what does this cause
- via inhibiting the kinase:ADP (low energy), Pyruvate, CoASH, NAD+
- By activating the phosphotase: Insulin, Ca++
- This is when your body has low energy or you have just eaten a high carb meal or you have a build up of the substrate for PDH
what macromolecules feed into the TCA cycle
- carbohydrates
- fatty acids
- amino acids
where does the great majority of energy derived from glucose come from?
-TCA cycle
what products do you get from the TCA cycle?
- 3 NADH (isocitrate dehydrogenase, a-KGDH, malate dehydrogenase)
- 2 CO2 (isocitrate DH, a-KGDH)
- FADH2 (succinate DH)
- GTP (succinyl CoA synthetase)
Regulatory enzymes of the TCA, just their names
- citrate synthase
- isocitrate DH
- a-KGDH
- malate dehydrogenase
what regulates citrate synthase
- activator: increased ADP
- inhibitor: NADH, SuccCoA, ATP
what regulates isocitrate DH
- activator: ADP, Ca
- inhibitor: NADH, ATP
what regulates a-KGDH?
- activator: Ca
- inhibitor: NADH, SuccCoA
what regulates malate dehydrogenase?
-inhibitor: NADH
what regulates PDH?
- activators: AMP, CoA, NAD+, Ca++, insulin
- inhibitors: ATP, AcCoA, NADH, fatty acids
anaplerotic pathways into the TCA cycle (7)
- glutamate into aKG
- I,M,V odd-chain fatty acids into succinyl CoA
- A,P,Y into fumerate
- transamination of amino acids into OAA
- PEP into OAA via PEP carboxykinase
- Pyruvate into OAA via pyruvate carboxylase
PPS generates what two important products?
NADPH and ribose-5-P
recognition by trypsin, chymotrypsin, and elastase
- trypsin: positive charge
- chymotrypsin: big hydrophobis
- elastase: small hydrophobic
- these are serine proteases
what part of the serine protease attacks
-serine 195
serine proteases are
-hydrolyases
delta G double dagger
- this is the energy of activation
- the larger it is, the slower the reaction
catabolism
-breaking down fuel/food to make ATP
anabolism
- using ATP to build up complex biosynthetic molecules
- active transport
- mechanical work
Km
substrate concentration at 1/2 Vmax
enzyme activity respons the most to substrate concentrations where
-near the Km
Vmax is used to determine
the amount of enzyme
delta G is sensitive to
-substrate concentration
delta G not is
constant because the concentrations are worked in already
thrombin is made where, what does it reuire, for what, how is it activated, what does the activated form do
- on the membrane surface
- vitamin K and Ca dependent gamma carboxylation
- two proteolytic cleavages result in activated, solube thrombin
- thrombin catalyzes the conversion of fibrinogen to fibrin
elastase is inhibitted by what in the lung
-alpha 1 antitrypsin / alpha 1 antiproteinase
what secretes elastase in the lung
-neutrophils
what does defective alpha 1 antitrypsin lead to
-no inhibition of elastase, degradations of the lung tissue and therefor emphysema
competitive inhibs interfere with…
-substrate binding
Ki
- the lower this value is, the more effective the inhibitor
- lower number = tighter binding
- this is exactly how Km relates to substrate affinity
how would you define a Km for an allosteric enzyme
-it would be an “apperant” Km
what do allosteric enzymes typically have?
- binding sites for affector molecules that change the enzyme confirmation
- either increasing or decreasing activity
allosteric enzymes often regulate…
the first step of a reaction pathway that is dedicated to making a specific compound for the pathway
what cyclins/CDK are involved in pRB phosphorylation
- Cyclind D/E with 2/4/6
- this allows E2F to begin transcription
what can activate p53 and then what can it do?
- oncogenes and DNA damage can activate it
- then it can initiate apoptosis or inhibit Cylcin/CDK complexes via p21
what chromosomal changes are associated with burkitts lymphoma
-translocations
burkitts lymphoma translocation
-between chromosome 8 and one of three chromosomes containing genes that encode Ab molecules
burkitts lymphoma is associated with q
epstein bar virus
what is the gene on chromosome 8 that gets moved in burkits lymphoma
- Myc
- encodes a transcription factor
- once transloacted, it is constitutively expressed
What can transformation by a DNA tumor cause?
sequestering of pRb and p53 so that the cell is constitutively in proliferation mode
HPV
- E7
- E6
binds up tumor supressor proteins
-E7=pRb
=E6=p53
mutant epidermal growth factors may…
constantly stimulate growth
Ras
- oncogene
- when bound to GTP, it is active and causing the cell to proliferate
- mutant for can be stuck in the GTP bound form
- this is regulated by GAPs (GTPase activating proteins)
Neurofibromatosis
- this is caused by a mutation in the NF1 gene which encodes neurofibromin which is a GAP
- a mutation in NF1 is believed to result in a constantly active Ras
- associated with cafe-au-lait spots
the six changes in the cell that lead to cancer
- self sufficiency in growth signals (Ras)
- insensitivity to anti growth signals (lose Rb)
- evading apoptosis (produce IGF)
- limitless replicative potential (telomerase)
- sustained angiogenesis
- tissue invasion and metastasis
compartments of the mitochondria
- outer membrane,
- intermembrane space
- inner membrane
- matrix
mtDNA
- small, circular
- 13 oxphos proteins
- some RNA’s
majority of mitochondrial proteins are
-transcribed from genomic DNA and imported from the cytoplasm using TIM and TOM proteins
1st step of ox phos
- electron transfer from NADH and succinate to O2
- this generates NAD+ and H2O
- complexes 1-4
2nd step of oxphos
- generation of the electrochemical proton transmembrane potential (negative and alkaline on the matrix side, pociditive and acidic on the intermembrane space side)
- only complexes 1,3, and 4 have proton pumps, NOT 2!)
3rd step of oxphos
- use proton motive force to synthesize ATP from ADP using ATP synthase
- complex 5
what carries electrons from complex 1 and 2 to 3
-coQ
what carries electrons from 3 to 4
-cytC
what does the word coupling refer to
- the codependence of the rates of respiration and ATP synthesis
- ie we can not change the rate of respiration without changing the rate of ATP synthesis and vice versa because the gradient is self-limiting
rate limiting steps of oxphos
- primary: how much ADP we have
- respiratory chain substrates
permeability to NADH
- the inner membrane is impermeable to it
- uses the glycerol phosphate and malate-aspartate shuttles to overcome this
glycerol phosphate shuttle
- DHAP is made into glycerol 2 P using a NADH from glycolysis
- therefore, glycerol 3 P is reduced
- glycerol 3 P then makes contact with a protein on the inner membrane which reduced NAD+ in the matrix using glycerol 3 P which makes matrix NADH and reproduces DHAP
malate-aspartate shuttle
- OAA is reduced to malate in the cytoplasm using NADH from glycolysis
- malate is then allowed to go through the inner membrane into the matrix where is reduces a NAD+ to NADH and is converted back to OAA
- this OAA is then converted to Asparte which can be shuttled back across the inner membrane to be converted back to OAA in the cytoplasm in order to carry more electrons
flavin in oxphos
-prosthetic group on C1
heme in oxphos
-this is found in cytC and carries e-
Fe-S clusters
-found in C1,2, and 3
inhibition of C1
does not completely shut down oxphos
-wherease inhibition of 3 and 4 do
