BIOCHEMISTRY- Processes Videos Flashcards
From where is energy extracted?
From food via oxidation
Which are the processes of energy extracted from food?
- Hydrolyzed in the GI tract to a diverse set of monomeric building blocks
- Building blocks are degraded to a common metabolic intermediate, acetyl CoA
- Citric acid cycle oxidizes acetyl CoA to CO2
- Extraction of energy from food is oxidative phosphorylation in which the energy of NADH and FADH2 is released via the ETC and used by an ATP synthase to produce ATP
Which cycle oxidizes acetyl CoA to CO2?
Citric acid cycle
What is increased every time metabolism is increased?
CO2
What is the first substrate of TCA cycle?
Acetyl CoA
Which are the products of TCA cycle?
2 CO2, 3 NADH and FADH2
What activates NADH and FADH?
Dehydrogenases
What do NADH and FADH2 produce?
Electrons
What happens to the electrons produced by NADH and FADH?
The electron transporter chain take them
Where does Electron Transporter chain work?
In the inner mitochondrial membrane
Who is the acceptor of electrons?
O2
Which is the most common cause of damage tissue?
Hypoxia–> Decrease the production of energy
Three main causes of hypoxia
Vessels
Heart/lung
Red blood cells
Which enzyme derives the energy of the electron transport chain?
ATP synthase
What is the function of ATP synthase?
Derives the energy of the E;ectron Transport chain to make ATP
Which is the process of how ATP is produced by ATP synthase?
By oxidative phosphorylation
What are the main sources of Acetyl CoA?
Carbohydrate → Glucose → Pyruvate
Fat → Fatty acids
Protein → Aminoacids
Which is the process where GLucose becomes Pyruvate?
Glycolysis
What else is produce in Glycolysis?
ATP (in the abscense of Oxygen)
From where is ATP produce in the abscense of Oxygen?
From anaerobic Glycolysis
Substrate Level phosphorylation
Which enzyme is required from pyruvate conversion to Acetyl CoA?
PDH
When do Carbohydrates produce Acetyl CoA?
After a meal
When do Fat produce Acetyl CoA?
Between meals
Process that leads from fatty acids to Acetyl CoA?
β oxidation
Which hormone is present after a meal?
Insulin
Which hormones are present between meals?
Glucagon, Cortisol, epinephrine
Who are the main source of Acetyl CoA when you are between meals?
Fatty acids
Which is the only organ that uses Fatty acids after a meal?
Heart
What is GLycogen?
Taking a lot of glucose and forming a large chain of glucose
Storage form of glucose
Which hormone forms glycogen?
Insulin
What controls the formation of glycogen?
Insulin
High levels of ATP from burning sugar
Which is the starting point of Gluconeogenesis?
In the liver starting from pyruvate
From where can we get pyruvate?
From aminoacids, alanine by alanine transmaminase
From lactate coming from Red blood cells by cori cycle
Which organ produces Ketone bodies?
Liver
Which organs use ketone bodies to make Acetyl CoA?
Heart, kidneys
Once ATP is high, what is the effect of insulin?
Make glycogen or make fat
Once ATP is high, what is the effect of Glucagon?
Make ketones
Make glucose thorugh gluconeogenesis
Release glucose from glycogen through gluconeogenesis
Which food are high carb meals?
Starch, sucrose, lactose
After digestion of starch, sucrose and lactose by amylase… What are the results?
Maltose, isomaltose, sucrose, lactose
Who breaks maltose, ismolatose, sucrose and lactose?
Brush border disaccharidases
What are the products of brush border disaccharidases?
Glc, Gal, Fru (Monosacharides)
Which forms of carbohydrates can’t be absorbed?
Disacharides, they have to be monosacharides
How are monosacharides absorbed in the intestinal lumen?
By active transport by Na+/ Gl symporter
Which are the insulin dependent tissues?
Liver, adipocytes anb muscle
Which GLUT is very associated with insulin?
GLUT 4
What is the effect of increased insulin related to GLUT 4?
Increases the number of plasma membrane GLUT 4 transporters
Where are GLUT 4 found?
In muscle and adipose tissue
What is the effect of GLUT 4?
Glucose removal out of Blood
How are GLUT 4 made?
Cytoplasmic vesicles with membrane bound GLUT 4 transporters
Which is the sign for GLUT 4?
Insulin effect, opening the vesicle to free GLUT 4
How is responsable of opening the vesicle who frees GLUT?
Insulin binds to the receptor → All the systems activated → PI3 kinase → Open vesicles
What is the effect of insulin in the adipose tissue?
↑ LPL (lipoproteinlipase) → break down tryglycerides and Fatty acids
Why do we require LPL?
Because Tryglycerides can’t go into the membrane; so membrane they break down to fatty acids pass thorugh the membrane and once again inside the adipocyte become tryglyceride and stored
Where do we find GLUT 1?
Most tissues (brain, red cells)
Where do we find GLUT-2?
Liver, Pancreatic β cells
Where do we find GLUT 3?
Most tissues
Where do we find GLUT 4?
Skeletal muscle
Adipose tissue
Which GLUT manage basal uptake of glucose?
GLUT-1 and GLUT-3
What is the function of GLUT-2?
Uptake and release of glucose by the liver; β cell glucose sensor
It’s function is insulin stimulated glucose uptake; stimualted by exercise in skeletal muslce
GLUT 4
Which are the normal glucose concentration?
4-6 mM (72-110 mg/ dL)
Which are the GLUT that transport GLucose at a constant rate regardless of blood GLucose?
GLUT 1 and GLUT 3 (1mM value)
km glucose levels of GLUT 2
15 mM
Which GLUT serves as a glucose sensor in the pancreas?
GLUT 2 in β pancreatic cells
What is the process of glucose once it gets to the pancreas?
- Enter β cell by GLUT 2
- GLucokinase phosphorylate GLucose
- Glucose phosphate enters glycolysis in Mitochondrion
- Oxidation is done making a lot of ATP
What is the effect of high ATP levels in β pancreatic cells?
Closes K ATP channel → Decreased membrane depolarization → Opens Ca2+ channel (calcium enters pancreatic cells) → Activates ATPases → COnversion of proinsulin to insulin → insulin is released out of the pancreas into blood stream
How is insulin secretion?
Biphasic:
- Preformed insulin (occurs within 10-15 minutes)
- Newly synthesized insulin (last up to 2 hours)
Which enzyme converts Glucose to Glucose 6 P?
Hexokinase
Who regulates Hexokinase?
The product which is Glucose 6P
Which enzyme is found in the liver and has the same activity as Hexokinase?
Glucokinase
What is the function of Kinase?
Phosphorylate the product = ATP → ADP
Who regulates Glucokinase?
Insulin
Which is one of the most important enzymes in glycolysis?
PFK-1 (Phosphofructokinase- 1 )
What is the effect of PFK 1?
Conversion of Fructose 6P to Fructose 1,6 bis P
What is the importance of PFK-1?
Is highly regulated by a lot of things but the main ones: AMP (+), ATP (-) and Citrate (remember this last one is pruduced during Kreb cycle)
From all the processes of glycolysis, how do we get to Pyruvate?
From Phosphoenolpyruvate, thanks to Pyruvate kinase effect it becomes pyruvate
Which enzyme makes Acetyl CoA from Pyruvate?
Pyruvate dehydrogenase
Which are the main pathway that Acetyl CoA can cause?
TCA of Fatty acid synthesis
Type of enzyme defect found with Pyruvate defect?
Partial defect
Pathologies associated with Pyruvate kinase
Hemolytic anemia
Increased BPG
NO HEINZ BODIES
What is the function of Pyruvate kinase?
It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding one molecule of pyruvate and one molecule of ATP
Second most common cause of Hemolytic anemia
Pyruvate kinase deficiency
Which are the only metabolic pathway remain in Erythrocytes?
Glycolysis
Hexomonophosphate shunt
Why do RBC require GLycolysis?
Because they require energy for the pumps of channels in the memebrane to maintain a gradient, of not the cells shape is lost which leads to hemolytic anemia
Why do erythrocytes require NADH?
Antioxidant
Conversion of Methemoglobin to hemoglobin. Remember that NADH gives electrons and those electrons are required for the conversion of Fe+3 (methemoglobin) to Fe2+ (normal hemoglobin)
What is the effect of 2,3 BPG in the RBC?
↓ O2 affinity for Hb
↑ O2 unloading
What is found in erythrocytes structure in G6P deficiency?
Heinz bodies
Most common cause of Hemolytic anemia
G6P deficiency
What are the effects after high carb meal?
↑ ATP
↓ PFK-1
↓ GLycolysis
Where is PFK-2 6-P found?
Liver
What is the result of PFK-2?
Fructose 6P → Fructore 2,6 P
What is the function of PFK-2?
Force PFK-1 to work in the liver to conclude forming fatty acids
Who regulates positively PFK-2?
Insulin
Who turns off PFK-2?
Glucagon
How many ATP are generated in anaerobic glycolysis?
2
Where does 2,3 BPG bind in the RBC?
To β subunits
?What is the function of 2,3 BPG
Kick out the oxygen of the erythrocyte in order to oxygenate tissues
Does 2,3 BPG bind to HbF?
NO
What is the function of Lactase?
Convert Lactose to Glucose and Galactose
Where does Galactose enters?
Liver and Brain
Which enzyme catabolizes Galactose?
Galactose kinase and the product is Galactose 1-P in the liver and the brain
What enzyme is required for galactose1-P to become Glucose 1-P?
Gal 1- P Uridyl transferase
Which enzymes might be deficient in Galactosemia?
Galactokinase
Gal 1- P Uridyl transferase
Clinical findings of Glacatokinase deficiency
Cataracts early in life
Clinical findings of Gal 1- P Uridyl transferase deficiency
Cataracts early in life Vomiting, diarrhea after lactose ingestion Letharghy Liver damage, hyperbilirubinemia Mental retardation
If galactose accumulate where does it go?
To the lens
Once galactose goes to the lens what happens?
Aldose reductase catabolizes it, becoming Galactiol (Polyol)
What is the effect of Galactiol in the lens?
It gets trapped causing cataracts and swelling
What explains cataracts in diabetics?
Glucose accumulate in the lens becoming sorbitol thanks to aldolase reductase
What are the components of Sucrose?
Glucose+ Fructose catalized by sucrase
Where does Fructose go?
Liver and kidney
In fructose metabolism which are the main enzymes?
Fructokinase and aldolase B
What does Fructokinase catalize?
Fructose to Fructose 1-P (phosphorylates)
What does Aldolase B catalize?
Fructose 1P → Glyceraldehyde or DHAP
Alternative name for fructokinase deficiency
Essential fructosuria
Findings of Aldolase B deficiency
Lethargy, vomiting Liver damage, hyperbilirubinemia Hypoglycemia Hyperuricemia Renal proximal tubule defect (Fanconi)
Alternative name for Aldolase B deficiency
Hereditary Fructose Intolerance
Which enzyme catalizes the conversion of Pyruvate to Acetyl CoA?
Pyruvate dehydrogenase
Where is Pyruvate dehydrogenase located?
In the Mitochondria
What does Pyruvate dehydrogenase do?
Two paths:
Take the electrons of Pyruvate; from NAD form NADH and generate 3 ATP and CO2
Becomes Acetyl CoA enters TCA cycle and form more ATP
Which is the main characteristic of Pyruvate Dehydrogenase?
Highly regulated
Who regulates Pyruvate dehydrogenase?
Acetyl CoA (the product- negatively)
What does Pyruvate Dehydrogenase need to work?
Tender Loving Care For Nancy Thiamine pyrophosphate (TPP) form vitamin Thiamine Lipioc acid Coenzyme A (CoA) from panthothenic FAD (H2) from riboflavin NAD (H) from niacin
Which enzymes require the mnemonic “Tender Loving Care For Nancy”?
Pyruvate Dehydrogenase
α ketoglutarate
Branched-chain ketoacid dehydrogenase
Why can IV glucose solution kill alcoholic patients?
Because of Lactic acidosis
Why IV solution cause lactic acidosis in alcoholic patients?
Thiamine deficiency → Bad function of Pyruvate dehydrogenase → Pyruvate not becoming Acetyl CoA → Pyruvate accummulate out of mitochoncria in the cytoplasm → Lactic dehydrogenase start working on accumulated Pyruvate → Lactic Acidosis → Dead
How many ATPs are generated by Acetyl CoA in Kreb Cycle?
12 ATP per Acetyl CoA, but glucose generate 2 acetyl CoA so 24 ATP total
In TCA cycle what is the function of α ketoglutarate dehydrogenase?
Catabolize α ketoglutarate to Succinyl CoA producing CO2 and NADPH
What does α ketoglutarate need to work?
Tender Loving Care For Nancy Thiamine pyrophosphate (TPP) form vitamin Thiamine Lipioc acid Coenzyme A (CoA) from panthothenic FAD (H2) from riboflavin NAD (H) from niacin
Which is the most important enzyme of Kreb cycle?
Isocitrate dehydrogenase
What regulates Isocitrate dehydrogenase?
ATP, NADH (low ATP, NADH → ↑ Isocitrate dehydrogenase; High ATP, NADH → ↓ Isocitrate dehydrogenase)
Once Isocitrate dehydrogenase is inhibited what is the effect?
Isocitrate accummulates in the mitochondria → Citrate spills out to cytoplasm → Citrate accumulation on cytoplasm → Inhibition of PFK 1 (Top regulator of glycolysis)
Alternative names for Coenzyme Q
Ubiquinone
CoQ
CoQ10
What is Coenzyme Q?
A lipid
In oxidative Phosphorylation pathway in electron chain reaction which are the bypass reaction for Ubiquinone?
Succinate dehydrogenase FADH2 Complex II (krebs cycle)
Fatty Acyl CoA dehydrogenase FADH2 (β oxidation)
GLycerol-P shuttle FADH2 (Glycolysis)
NADH dehydrogenase Comple I
Which enzyme does β oxidation?
Fatty Acyl CoA dehydrogenase FADH2
During Oxidative phosphorylation on the mitochondria which drugs inhibit NADH dehydrogenase Complex I?
Barbiturates Rotenone (an insecticide)
How do Barbiturates and Rotenone inhibit the production of ATP?
Stop electron flow from NADH dehydrogenase Complex I to Coenzyme Q (Ubiquinone)
In oxidative Phosphorylation who affects complex IV cytochrome oxidase?
Cyanide
How does cyanide kill?
Because it binds Fe in its Fe3+ form in Complex IV, then when electrons come down in electron transport when they get in complex IV, electrons can’t go to complex IV in the Fe3+ because there is cyanide, so electrons back up (electrons flow stop) so no ATP is made
What are the antidotes for cyanide poisoning?
1) Nitrite
2) Thiosulfate
How does Nitrite work as antidote for Cyanide poisoning?
1) Nitrite (oxidative agent, removes electrons) → making Methemoglobin
Hb (Fe2+) + Nitrite → Hb (Fe3+)
Once Methemoglobin is formed (thanks to nitrite), cyanide will look for Fe3+ and bind to it, instead of binding to the Fe3+ of the Complex IV
How does Thiosulfate work as antidote for Cyanide poisoning?
Will convert cyanide to thiocyanate (less toxic)
What does CO bind to?
To Fe2+ form
How does CO affect Complex IV?
Because it binds to Fe2+ form of the complex IV, preventing the electron to bind to Fe2+, so no ATP generated
What is the function of the F0 channel?
Transportation of protons to the F1 compartment in the phosphorylation of ADP to ATP
How does Oligomycin inhibit ATP formation?
By inhibiting F0 channel, so no proton transportation to F1 compartment, so no ADP Phosphorylation to ATP
Which drug inhibits F0 channel in Mitochondrioa in ATP formation?
Olygomycin
Which antiporter system moves ATP out of the mitochondrioa?
ATP/ ADP translocase
What is the function of ATP/ADP translocase?
Works as Antiporter moving ATP out of the mitochondria and introducing ADP once again into the mitochondria
Who regulates Oxidative phosphorylation?
ADP (controls rate- respiratory control)
In the oxidative phosphorylation process who works as an uncoupler?
2,4 DNP
What is the effect of 2,4 DNP?
Weak base which allows H+ back in matrix, so no ATP production, because protons do not reach F1 compartment
Which drugs are consider uncouplers?
Aspirin (High dose)
Thermogenin
How is glycogen formed?
By α 1, 4 glucose attachment to another α 1,4 glucose, thanks to glycogen synthase
After 12-13 glucose residues, a branching enzyme make it α 1,6 glucose linkage
Who positively regulates glycogen synthase? Where?
Insulin, in the liver and muscle
Who turns off glycogen synthase?
Glucagon
Which enzyme breaks down Glycogen in order to form Glucose 1 P?
Glycogen Phosphorylase
What is the function of Glycogen Phosphorylase?
Adds inorganic phosphate to cleave sugar bonds converting Glycogen to Glucose 1-P
Which are the two most important phosphorylases?
Glycogen phosphorylase
Purin Nucleoside Phosphorylase
Which is the accesory enzyme that helps Glycogen Phosphorylase?
Debranching enzyme, which debranch the α 1,6 Glucose, depolarizing
Who regulates Glycogen Phosphorylase?
Glucagon (Liver)
Epinephrine (liver, muscle)
AMP (muscle)
Who inhibits or dephosphorylates Glycogen Phosphorylase?
Insulin
Which enzyme catabolizes the conversion of Glucose 6 P to Glucose?
Glucose 6 Phosphatase
Where can we find glucose 6 Phosphatase?
In the liver
In the muscle what happens to GLucose 6 P?
Enters glycolysis, becoming pyruvate in the end generating Lactate or ATP, CO2 + H20
Where is glycolysis made?
In the muscle
What is purpose of glucose 6- Phosphatase found only in the liver?
Because it maintains glucose in the body
Glycogen storage diseases
von Gierke
Pompe
Cori disease
Andersen disease
Which pathology is associated to GLucose 6 phosphatase deficiency?
von Gierke disease (GLycogen storage disease)
Cardinal clinical features of von Gierke disease
Severe hypoglycemia, lactic acidosis, hepatomegaly, hyperlipidemia, hyperuricemia, short stature, doll like facies, protruding abdomen, emanciated extremities
How is glycogen synthesis in von Gierke disease?
Normal
Deficient enzyme in Pompe disease
Lysosomal α 1,4 glucosidase
Cardinal clinical features Pompe disease
Cardiomegaly, muscle weakness, death by 2 year
How is glycogen synthesis in Pompe disease?
Glycogen like material in inclusions bodies
Deficient enzyme in Cori disease
Glycogen debranching enzyme
