Thompson Flashcards
What is the difference between and aldehyde and ketone group
aldehyde has double bond with O on the end of the structure and Keto is in the middle of the C chain
cause and symptoms of Pellagra
Niacin deficiency. Niacin is a precursor to Nad+
4 Ds: Diarrhea, Dementia, dermatitis, death
Isomer
Enantiomer
Epimer
Same formula, different structure
Mirror Images
Differ in position of hydroxyl group around asymmetric carbon
what makes a sugar a reducing sugar?
when the oxygen on the anomeric carbon is not attached to another structure- can be oxidized
How do plants store glucose? What kind of bond
As Amylose with alpha 1-4 linkages
Salivary alpha amylase
Hydrolyzes random alpha 1-4 bonds. inactivated by the low pH of the stomach
what bonds do intestinal disaccharides break
alpha 1-6 glucosidase activity. ex: lactase, maltase
How are glucose and galactose brought into the epithelial cells during digestion
SGLT-1. Sodium Dependent Glucose Cotransporter. Secondary active transport. requires conccurent uptake of sodium ions
How is fructose brought into epithelial cells during digestion
GLUT 5. An E and Na Independent transporter
what are ways phosphorylation affects metabolic pathway
the net negative charge traps the molecule inside the cell, conserves E from breaking phophate bonds, commits to further metabolism
How do monosaccharides leave epithelial cells for circulation
GLUT 2 they all do.
What is the difference between hexokinase and glucokinase
glucokinase is only in the liver. Hexokinase most abundant when glucose levels are low because the brain gets glucose first.
what is the rate limiting step of glycolysis, what inhibits/activates it?
PFK-1. Inhibited by ATP
Activated by: AMP, F-2,6-P
After which step in glycolysis is there an important side reaction relevant to Hb
1-3 bpg cna be converted to 23 bpg by mutase, phophotase can convert 23bpg to 3pg. SKIPS the phophoglycerate kinase substrate level phophorylation
What is the last step of glycolysis? What activates/inhibits this enzyme
Pyruvate Kinase. INhibited by : Alanine, phophorylation due to cAMP in liver
Actiavted by: F-1,6-P
How does cAMP affect F26bp levels and how does that affect glycolysis
With glucagon levels high cAMP activates protein kinase A which phophorylated PFK2/FBP-2. When phophorylated F-26bp is not made. reducing glycolysis levels.
Which enzyme is reponsible for anaerobic glycolysis
Lactate Dehydrogenase
what enzyme converts pyruvate to oxaloacetate? why would it do that
pyruvate carboxylase. activated by acetyl coA- it refills intermediates for TCA cycle and gluconeogenesis
What is the enzyme that converts pyruvate to acetyl coA? what are the cofactors?
Oxidative decarboxylation of pyruvate is done by pyruvate dehydrogenase
The cofactors are: TPP, CoA, Lipod Acid, FAC, NAD+
It is inactive when phophorylated. The kinase that phophorylates PD is activated by NADH and Acetyl Coa (hence they decrease pd activity) and inactivated by ADP
What happens when pyruvate dehydrogenase is defective
Pyruvate and Lactate build up causing congenital lactic acidosis
Where are all of the enzymes of the TCA cycle? What is the exception
Mt Matrix except succinate dehydrogenase
What is the highest regualted step of the TCA cycle
Isocitrate dehydrogenase. Activated by ADP, CA; Inhibited by NADH, ATP
Which TCA enzyme has similar cofactors to PD complex? what activates/inhibits it
alpha ketogluterate complex
act: Ca
inhibited by: NADH, Succinyl CoA
Which four enzymes in TCA create NADH, FADH2
Isocitrate dehydrogenase: NADH
Aketogluteralte dehydrogenase: NADH
Malate Dehydrogenase: NADH
Succinate Dehydrogenase: FADH2
Which TCA step creates a GTP
Succinyl Coa synthetase/succinate thiokinase
What is an anapleurotic reaction
to fill up intermediates of depleted cycle
During ETC are hydrogens being pushed into the matrix or intermembrane space
intermembrane space
How does the redox potential affect the ETC
the more negative the higher tendancy to lose electrons. electrons move from negative to positiv eredox potential during ETC
What is complex 1 of the ETC
NADH Dehydrogenase. It uses Flavin (FMN) to transfer 2 electrons to CoQ
It has Fe-S at the center.
What is complex 2 of the ETC
Succinate dehydrogenase. Electrons go to FADH2 to Fe-S to CoQ. Does not pump protons.
What is CoQ of the ETC
Ubiquonone. Accepts H+ from Complex 1 and 2 and deliver them to complex 3 (cytochorme bc1)
Complex 3 of ETC
cytochrome bc1 moves electrons to cytochorme c and pumps protons
cytochrome c
between complex 3 and 4. in the intermembrane space.
complex 4
cyt a +a3, cytochrome oxidase. Contains Cu, Reduces O2 to H2O
complex 5 of ETC
F0 domain pumps protons where F1 domain converts ADP to ATP
what does the incomplete reduction of oxygen make? ex: due to block of ETC
reactive oxygen species
How does Amytal ROtenone, Antimycin A, CN-, CO and SOdium Azide affect metabolism
They block the ETC at different points of electron transfer. Amytal ROtenon blocks transfer between FMN and CoA, Antmycin A blocks between ct bc1 and cyt c, the rest block between cyt a +a3 to O2
How are reducing equivalents taken through the inner mitochondrial membrane
- Glycerophophate shuttle 2. Malate Aspartate Shuttle
How does the glycerophophate shuttle work? How many atps are made for every NADH
The electrons are converted to G-3P in the cytosol from DHAP. In the matrix. G3P goes back to DHAP but only FADH2 is made so only 2 ATPS are created.
How does the malate aspartate shuttle work?
Is able to produce NADH in the mt matric so 3 ATPs can be produced. Malate dehydrogenase.
How does the body deal with H2O2
G-SH Reduced Glutathione. G-S-S-G is mad eby glutathione peroxidase and converted to G-SH by NADPH
Superoxidase Dismutase. What is one disease caused by a defect in this.
Turns O2- into H2O2. ALS
Where is the PPP most active
RBC (For glutathione synthesis)
Adrenal gland, liver, testes, adipose tissue, ovary for steroid/fa synthesis
p450 in the liver
where does PPP take place
cytosol
Do phagolysosomes need NADPH
Yes. At least WBC in some phagocytosis used NADPH oxidase to make O2 radical to destroy microogranism
Which neurotransmitter synthesis requires NADPH
Nitric Oxide (NO). It is a relaxing factor, prevents platelet aggregation, mediates bacteriocidal things. It is created when Arginine is converted to Citrulline.
What are the two phases of the PPP
Oxidative (makes NADPH)
Non-oxidative
Wha tis the enzyme of the oxidative portion of PPP. What does it make?
Glucose 6 Phosphate Dehydrogenase. Turns glucose 6 phosphate to Ribulose 5 Phophate . Releases Co2, 2 NADPH
What happens in Glucose 6 phophate dehydrogenase deficiency
It impairs the RBC ability to make NADPH and you end up accumulating free radicals. Leads to hemolysis.
Usually not a problem until cretain drugs/infections/diet trigger oxidant stress.
There might be some protection for malaria bc red cells die faster
Is ATP used or made in the PPP
No
What are the enzymes of the non-oxidative portion of PPP
transketolase (uses TPP) 2C units
transaldolase 3C units
In order to make one glucose molecule from 2 pyruvate how many ATP are required? For which enzymes?
6 ATP. 2 for pyruvate carboxylase, 2 for PEP carboxylase, 2 for phosphoglycerate kinase
How do you convert pyruvate to PEP in gluconeogensis
two enzymes (unlike glycolysis).
- Pyruvate carboxylase -needs biotin, 2 ATP makes OAA
- PEP caboxylase- needs 2 GTP
Which enzyme in gluconeogenesis requires biotin
pyruvate carboxylase
Which two enzymes in end part of gluconeogeneisis are different than glycolysis
Fructose 1,6 bisphosphatase, glucose 6 phosphotase
Are lactate and alanine used in gluconeogenesis?
Yes they are both converted to pyruvate and used. By lactate dehydrogenase and alanine aminotransferase
Where is pyruvate carboxylase? Why is this important
In the mitochondria. If there is no lactate made and pyruvate is made into OAA first in the mt there needs to be additional steps to get reducing equivalents in the cytosol to be used in the G3P step.
How do cells without lactate get reducing equivalents in the cytosol for gluconeogenesis
OAA in the mt is converted to malate (requires NADH) and then shuttled outside of the mt. malate dehydrogenase in the cytosol reconverts it to OAA making NADH that can be used fpr G3P step.
Acetyl CoA affects gluconeogenisis by targeting which enzyme?
It activates pyruvate carboxylase
Which hormones stimulate PEP Carboxykinase in LIVER
glucagon/epi increase activity
insulin decreases activity
In the liver how are PFK-1 and F16phophatase affected by F26P
F26P stimulates PFK1 and inhibits F16Pase\
When glucagon is high in liver protein kinase A is activated which phosphorylates the PFK2/FBP2 enzyme inactivating PFK2. This means less F26BP because it is converted to F6P by the FBP2ase .
When PFK2/FBP2 is not phosphorylated there is more F,26BP and glycolysis is activated
How is the phophorylation of the PFK2/FBP2 enzyme different in muscle?
It leads to more F26BP. So when epi activates cAMP glycolysis is activated.
When glucose is low (insulin low, epi/glucagon high) do we increase glycolysis?
In liver no. in muscle yes
What is the main purpose of the Cori Cycle
Reconversion of lactate to glucose by liver. Each cycle requires 4 ATPs
It prevents lactic acidosis in anaerobic conditions.
What happens to ethanol after consuming alcohol
Converted to acetyl aldehyde by ethanol dehydrogenase. Produces NADH- leads to NADH build up in liver cytosol. This favors pyruvate to go to lactate, and OAA to malate.
less gluconeogeneiss intermediates.
Where are the glycogen stores that help maintain blood glucose levels
Kidney and Liver
What are the glyocgen bonds for branched and not branched
alpha 1,4 glycosidic mostly excpet branched alpha 1,6
where is glycogenesis
cytosol
What is glyocgenin?
Enzyme protein that is backbone of glycogen. It has a tyrosine residue where first glucosyl reidue is attached. It self catalyzes the first few glucosyl reides.
What is the source of every glucosyl residue added to growing glycogen? What enzyme makes theis
UDP-glucose. Made from Glc-1-Phosphate and UTP with UDP glucose phophorylase. It si very energetically favorable
After the first few glucosyl residues are added which enzyme does the rest
glycogen synthase
What enzyme creates branches in growing glycogen chain? about how often is there a branch
Branching Enzyme. it removes 6-8 residues and reattaches them. Occurs about every 8 residues
How do you get Glc 1 P
From G6P and phosphoglucomutase
FOr glycogen degradation which enzyme cleaves 1-4 bonds and which does 1-6 bonds
Glycogen phophorylase cleaves alpha 1-4 bonds creating Glu-1P
Debranching Enzyme removes the last 3 residues and puts them on main chain. A single 1-6 residue is attached and relased as free glucose.
Is glycogen elongation on reducing ends or non-reducing ends
non-reducing ends
What is glycosidase? what disease is caused by a lack of it
Hydrolyses glycosidic bond in lysosyme. Pompe Disease- leads to accumulation of glycogen in lysosome. Affects the heart, Liver, muscle. usually die before age 2 from cardiorespitory failure.
Type 2 GSD. Glycogen looks normal.
What is Von Gierke
Type 1 GSD. affects liver and kidney. Due to glucose 6 phosphotase deficiency (or transport). Increased glycogen levels. Severe hypoglycemia, progressive renal disease. liver/hepato/renomegaly
What is Cori Disease
Type 3 GSD. A debranching enzyme deficiency. Muscle and liver have increased glycogen. Similar to Von Gierke but less severe. Hypoglycemia
Anderson Disease
Branching enzyme deficiency. Affects the liver and spleen. Glycogen has long outer branches.
Cirrhosis of the liver and death by age 2.
McArdle Disease
Type 5 GSD. Defective glycogen phosphorylase in MUSCLE. Cannot do anaerobic excercise.
Hers Disease
Defective glycogen phosphorylase in LIVER. Type 6 GSD>.
Like type 1 but milder because you can still do gluconeogenesis.
How does cAMP dependent protein kinase A affect gluconeogensis/degradation
It phophorylates glycogen phophorylase kinase which phophsorylates glycogen phophorylase leading to glycogen degradation.
(insulin does opposite)
How does Calcium affect glycogen phophorylase
In muscle it is realeased during contractin and activates glycogen phophorylase kinase —- glycogen degradation
In the liver it is relased during psychiatric stress and epinephrine signals for blood glucose– signaling for glycogen degradation
How can AMP affect glycogendegradation
under extreme conditions it can activate glycogen phophorylases without phophorylation.
Is glycogen synthase active when it is phosphorylated?
No, it is active when it is dephosphorylated. It is deactivated by cAMP PKA by phophorylating it.
What allosterically activates glycogen synthase
glucose 6 phosphate.
Where is fructokinase
Liver
When is fructose metabolism initiated? What happens to the fructose for it to enter the cycle
When metabolic pathways are not over satruated with glucose. It is phosphoylated to either F1P or F6p to enter
Which enzyme converts fructose to F1P and which to F6P
Fructokinase converts it to F1P in the liver and hexokinase converts it to F6P
What causes Essential Fructosria
A lack of fructokinase. Fructose is found in the urine but it is benign.
What causes Hereditary Fructose Intolerance
no Aldolase B which cleave F1P into glyeraldehye and dihydroxyacetonephophate.
Build up of F1P which ties up inorganic phophate
Severe hypoglycemia, liver and kidney damage. Cannot do gluconeogenesis and regenerate ATP
Sorbitol
Glucose can become sorbitol from aldose reductase (uses NADPH)
sorbitol then reduced to fructose from sorbitol dehydrogenase (NADH) in the liver and seminal vessicles
How is galactose metabolized
it is phophorylated first before it is metbolized. done by galactokinase, so it G1P
How is galactose-1-phosphate turned to glucose 1 Phosphate
Galactose 1 P Uridylytransferase (GALT)
deficiency: Classic Galactosemia
What are the symptoms of Galactokinase Deficicency
Cannot be made into galactose 1 P instead aldose reductase make glactical. Galactical build up causes cataracts
Classical Galactosemia
GALT deficiency cause a build up or gal1p and galacticol. Very severe, tie up of phosphate, jaundice, they do prenatal testing
What are glycoproteins and what are they used for?
Cell surface recognition, antigenicity, ECM, mucins.
they are proteins with oligosaccharides.
can have no or o glycosidic links.
What happens to sorbitol levels in diabetes
Increase which leas to cell swelling
Where are glycosaminoglycans commonly found
joints because of the structure. GAGs
What is the general structure of proteoglycans/mucopolysaccharides
GAGs attached to core protein and make bottlbrush shape, these are attached to hyaluronic to form long linear strucutres. GAGs are negatively charges so they repel each other
What is the cause of lysosomal storage diseases related to glycoproteins
Can be due to the degradation of mucopolysaccharides because GAGs are degraded in lysosomes.
What is the glucose transporter for Muscle and Adipose tissue
GLUT 4