TBL 10 Krebs cycle Flashcards
Glucogenic amino acids
Alanine, Cysteine, Glutamic acid, Glycine, Serine, Threonine, Tryptophan
Seri, Alan, Theo tryped Con Glue glyrilla
Glucogenic amino acids (from protein metabolism) and Glycerol (from fat metabolism)→
Pyruvate (cytosol)
how many ATP is produced during Anaerobic glycolysis?
2 ATP per glucose
Excessive accumulation of lactate can result in-
Excessive accumulation of lactate can result in– Lactic acidosis, which can manifest as generalized muscle fatigue/weakness (e.g, during walking) and convulsions
Gluconeogenesis is the pathway by which glucose is formed from non-hexose precursors such as ______
glycerol, lactate, pyruvate, and glucogenic amino acids
precursors involved in hepatic gluconeogenesis:
– Lactate (Anaerobic conditions)
– Alanine, Cysteine, Glutamic acid, Glycine, Serine, Threonine, Tryptophan, etc
(Glucogenic amino acids)
– Oxaloacetate (cytosolic)
– Triglycerides– Glycerol
Pyruvate (c/o Pyruvate dehydrogenase complex)→ converted into
Acetyl CoA (mitochondrial matrix)
Ketogenic Amino acids and Fatty acids→ can form ______
Acetyl CoA
fates of Acetyl CoA
i. primarily relate carbohydrate, protein, and lipid metabolisms to each other
ii. enter the Tricarboxylic acid (TCA, Citric acid) cycle
ii. be involved in the synthesis of– Acetylcholine, Cholesterol, Fatty acids, and Ketone bodies (Ketogenesis– common in type I diabetic patients)
krebs cycle inputs and outputs
– takes place in mitochondrial matrix
starts with Acetyl CoA, release stored energy through the ‘Acetyl CoA oxidation’
consumes acetate (as Acetyl CoA) and 2 H2O
generates 3 NADH molecules, 1 FADH2 molecule, and 1 GTP molecule– net yield of 12 ATP per each TCA cycle
– generates ‘Oxaloacetate’ at the end of the cycle
NADH– fed into_____
NADH– fed into ‘Oxidative phosphorylation’ during the Electron transport chain (ETC) pathway
– NADH and FADH2 are essential for oxidative phosphorylation
FADH2– transferred into the_______
– covalently attached to _______________
– facilitates ‘transfer of electrons to Coenzyme Q (Co-Q/ Ubiquinone
– Coenzyme Q (Ubiquinone), QH2 (Ubiquinol, Antioxidant)– substrate of Electron
transport chain (ETC)___
transferred into the Electron transport chain (ETC) pathway
– covalently attached to ‘succinate dehydrogenase’
– facilitates ‘transfer of electrons to Coenzyme Q (Co-Q/ Ubiquinone
– Coenzyme Q (Ubiquinone), QH2 (Ubiquinol, Antioxidant)– substrate of Electron
transport chain (ETC)
TCA cycle intermediates and related substances serve as substrates for many metabolic reactions: Acetyl coA can be converted into_____
Acetyl CoA can be converted into Aminoacids, Fatty acids, Cholesterol, Ketone bodies (acetoacetate, 3-beta-hydroxybutyrate, and acetone– Ketoacids)
Ketone bodies
Ketone bodies (acetoacetate, 3-beta-hydroxybutyrate, and acetone– Ketoacids)
Ketone bodies are produced from fatty acids in the liver and are then converted into____which is an alternative_____
. Ketone bodies are readily transported into tissues outside liver, where they are re-converted into acetyl-CoA
alternative source of energy in place of glucose during prolonged fasting, especially for brain— abnormally increased levels of ketone bodies can cause “Ketoacidosis”
intermediate in the krebs cycle ______ is directly/specifically utilized in formation of Amino acids (e.g, Glutamate [forms gamma aminobutyric acid [GABA], which is a excitatory neurotransmitter], Glutamine, Proline, Arginine)
α-Ketoglutarate
what amino acids are formed by α-Ketoglutarate
Glutamate [forms gamma aminobutyric acid [GABA], which is a excitatory neurotransmitter], Glutamine, Proline, Arginine)
Glu, Gln Arginine, Proline
angie pro glu glutamine
Succinyl CoA + Glycine→ utilized in formation of ________
Porphyrin/ Heme part of blood Hemoglobin
Stimulation of conversion of succinyl CoA into succinate lead to ↑ formation _______
of GTP
Protons (H+) are generated during formation of _____
NADH, which are later used in mitochondrial intermembrane space to power ATP synthesis during the ‘Oxidative phosphorylation (ETC)’
Oxaloacetate can be converted into ________(Gluconeogenesis– which is a pathway by which glucose is formed from non-hexose precursors during decrease availability of glucose inside the cells, e.g during severe hypoglycemia)
Phosphoenolpyruvate (PEP)
Krebs cycle activators
glutamine
glutathione
Fe
NADH
Carnosine
Physical execise
krebs cycle inhibitors
aconite inhibition: Zn excess
metals, excess Fe
metformin
Vit B12 Deficiency
how does Iron (↑ Fe+2) affect the krebs cycle
↑ conversion of Citrate into Cis-aconitate in TCA cycle
↑ conversion of Cis- aconitate into Isocitrate in the TCA by increasing the activity of mitochondrial Aconitase
Aconitase enzyme in the cells with abundant mitochondria (e.g, skeletal muscle cells) is stimulated by the iron supplementation to improve the muscular energy
_________ enzyme in the cells with abundant mitochondria (e.g, skeletal muscle cells) is stimulated by the iron supplementation to improve the muscular energy
Aconitase enzyme
↑ Fluoroacetate causes ________in TCA cyle
↑ Fluoroacetate→ ↓ conversion of Citrate into Cis-aconitate in TCA cycle
arsenic poisoning____
signs
. Arsenic poisoning leads to inhibition of pyruvate dehydrogenase complex (which can cause decrease conversion of pyruvate into acetyl CoA)
signs: Mees’s lines
The most common reason for long-term exposure is contaminated drinking water.
Malonate cause ______ in TCA
Malonate–→ ↓ conversion of Succinate into Fumarate
flores decrease certain mal sundays
flouroacetate decrease citrate (conversion), malonate decrease succinate conversion
insulin increases TCA
how does lipolysis affect
→ β-oxidation of Fatty acids (Skeletal and Cardiac muscles)→acetyl Coa—> TCA
Excessive caloric intake with food can result in obesity because _______
mt imbalance, an increase in oxidative stress, production of reactive oxygen species, inflammation, and apoptosis
Pyruvate dehydrogenase complex (PDHC) deficiency– Neurodegenerative disorder ( excess accumulation of pyruvate) leads to ________
fatal metabolic acidosis, neonatal-onset lethargy, hypotonicity, muscle spasticity, and neurodegeneration
because of conversion of excess pyruvate by lactate dehydrogenase into lactate l
__________ characterized by inability to perform motor skills previously acquired, loss of head control, poor suckling, recurrent vomiting, and loss of appetite
Leigh syndrome–
neurological disorder due to mutations encoding proteins of the PDHC )
viejito with a tilted head wearing a lei and cant suck on his drink in hawaii siting at dinner table with no appetite starts so vomit
Fumarase deficiency–
Fumarase deficiency– affected children
may have severe developmental delay, microcephaly, hypotonia, encephalopathy, seizures, psychomotor retardation, and failure to thrive
Mutations of isoCitrate dehydrogenase (IDH)–
several types of cancers (e.g, including leukemia, gliomas, and sarcomas)
what happens during the ETC
happens in Inner mitochondrial membrane contain series of protein complexes that transfer electrons from electron donors to electron acceptors via reduction and oxidation, and couples this electron transfer with the transfer of protons (H+) across the mitochondrial membrane
b) Mediates reactions (electron transfer) between NADH and FADH2 (generated in the TCA cycle) and O2 to power ATP synthase during oxidative phosphorylation– NADH and FADH2 (intermediate products of TCA cycle pathway) are essential most for the process of oxidative phosphorylation
basic principle of ETC
Each electron donor pass electrons to an electron acceptor of a higher redox potential, until final proton acceptor O2 (terminal electron acceptor in the ETC)
Each reaction releases energy because a higher-energy donor and acceptor convert to lower-energy products
↓
This entire process is termed as ‘Oxidative phosphorylation’
Electron acceptor (final) in aerobic conditions is _____
Electron acceptor in anaerobic conditions is____
o2
Sulphate
what happens in the first complex of ETC
complex 1: NADH dehydrogensase (NADH-ubiquinone/coenzyme Q oxido-reducatase )
accepts 2 protons from NADH and then goves it to coenzyme Q which then become reduced (coenzyme QH2) Ubiquinol
where does premature electron leakage occur?
Complex I is one of the main sites at which premature electron leakage to O2 occurs– one of main sites of ‘toxic free radicals (e.g superoxide)’ formation
what inhibits complex one?
Rotenone (Pesticide, fish poison)– inhibits Complex
Piericidin A (antibiotic agent→ inhibits NADH-Ubiquinone oxidoreducuctase)
Complex II–
Succinate dehydrogenase (Succinate Coenzyme Q reductase):
where doe the elctrons from FADH2 go?
do we gain any other electrons from anywhere else in the quinone pool?
In complex II, additional electrons are delivered into the quinone pool (Q) originating from succinate and transferred via FADH2 to Ubiquinone (Co-enzyme Q)-
fatty acids and glycerol-3-phosphate
Unlike complex I, no protons are transported to the intermembrane space in the complex II pathway
less energy to the overall ETC process
complex III
ubiquinol Cytochrome C oxidoreductase
or (coenzyme QH2 -cytochrome Creducatase)
complex III get electrons from coenzyme Q and pass then to cytochrome C
electrochemical gradient in the intermembrane is also formed here
Complex IV
Complex IV contain coordinated copper ions (Cu+) and several heme groups– cytochrome C oxidase uses copper ions while transporting the electrons
electrons are removed from cytochrome C and are transferred to O2 and protons (H+), producing of H2O
inhibitors of complex III
dimercaprol
naphthoquinone - by comp inhibition at the active site
antimycin A : causes complex III to prematurely leak electrons to O2, resulting in the formation of toxic ‘free radicals (e.g superoxide/O2-)’–
______highest redox potential
Oxygen (O2) has highest redox potential in human mitochondrial electron transport chain (ETC)
Carbon monoxide (CO), inhibits
cytochrome C oxidase (complex 4)
acute carbon monoxide poisoning (during fires)
cyanide inhibits
Complex 4
Chemiosmostic coupling hypothesis-
ETC and Oxidative phosphorylation are coupled by an electrochemical proton gradient across inner mitochondrial membrane
ETC pathway generates potential energy in form of an electrical potential across mitochondrial membrane. This store of energy is tapped when protons flow back across the membrane and down potential energy gradient, through ATP synthase in a process termed as ‘Chemiosmosis’. The ATP synthase uses this energy to generate ATP from ADP and Pi
ATP synthase system (Complex V),
Chemiosmotic hypothesis involves:
i. a membrane impermeable to protons
ii. electron transport by cellular respiratory chain pumps protons out of the mitochondria
iii. proton flow into the mitochondria depends on the presence of ADP and Pi inside the mitochondria
iv. reversible ATPase activity
Transport of electrons from redox pair NAD/NADH to the final redox pair of ½ O2 can be summarized as—
NADH + 2H+ + ½ O2→ H2O + NAD
how many ATP are produced per glucose
38
Blockage of mitochondrial ATPase activity can lead to ______
stimulation of neuronal apoptosis (programmed cell death)
Thermogenin
uncoupler of ETC and Oxidative phos
alternative flow of electron leads to to thermogenesis
Oxidative phosphorylation also produces reactive oxygen species (ROSs, e.g, superoxide and hydrogen peroxide)
Oligomycin A (antibiotic)–
selectively inhibits ATP synthase by blocking its proton pump,
2, 4-Dinitrophenol (antiseptic, non-selective bioaccumulating pesticide)
inhibit oxidative phosphorylation
