A 14 yo breast fead neonate fails to gain weight during infancy but mother continues ot breastfeed , the infant developes catarics an enlarged liver and a very funny retardation, galactosemia, and has high levels of galactose in the urine
What enzyme is defficent?
What food stuff is causing this for the baby?
Galactokinase defficency is causing galactose to build up in the urine
The lactose in the breast milk is beind degraded to glucose and galactose which is contributing to the problem
God forgive me for the retard joke
4 month old w hepatomegaly jaundice hypoglycemia and septic infection
What enzyme is deffective?
Galactose 1 phosphate udriyltransferase. These are classical symptoms of galactosemia
1. Jaundice is due to the livers inability to produce bilirubin
2. Galactose 1 phosphate inactivation of phosphoglucomutase contributes to hypoglycemia
3. Septic infection is common with G6P-UDT
An east african presents with jaundice and splenomegaly after eating flava beans, a blood smear reveals hemolysis,
What is the inactive enzyme and explain the symptoms
G6PDH catalyzes the oxidatie portion of the pentos phosphate pathway generating NADPH.
NADPH is required to mantain a reduced store of Glutathione which prevents oxidative damage to the red blood cells. (hemolysis)
Jaundice is from excess heme from the lysis of RBC's being converted to bilirubin and overwhelming the liver
Otherwise healthy child with 3x glucose in urine on a dipstick test
What hexose metabolism enzyme could be defective?
Fructose Kinase defficency results in fructose buildup in the urine which will make a glucose urine dipstick test show positive.
Healthy male has cataracts and galactosemia?
What is-a this?
Galactokinase defficency will result in galactose buildup in the blood and is converted in the eye developing cataracts.
Healthy patient is put on Primaquine (a drug known for inducing oxidative stress) he then developes sevire fatigue and experiences hemolysis. What is the problem?
He has defficent G6P UDT which prevents NADPH generation to mantain a stock of reduced glutathionine to combat oxidative stress.
What enzyme converts glucose to sorbitol?
34 year old with central obesity blood gluose is 258 mg/dl on OGTT and she has excess cortisol in her blood, what is causing her hyperglycemia?
PEPCK is transcriptionally regulated so increased circulating glucocorticoids will result in increased PEPCK gene expression. This will cause an increase in the conversion of OAA to PEP.
This is the commitment step of gluconeogenesis.
Which of the following would be indacitative of diabetes?
1. single random glucose level of 190mg/dl
2. Presence of reduced sugar in the urine
3. A fasting blood glucose level of 160mg/dl
4. A 2 hour oral glucose tolerance test of 210 mg/dl
5. A single fasting blood glucose level of 110 mg/dl
The only one that renders a diagnosis fo diabetes in a single episode is a 2 hour OGTT yielding blood glucose of 200mg/dl
Fasting glucose levels over 126 have to be observed atleast more than once for a diagnosis
Two fasting levels between 100- 125 indicate impared glucose tolerance.
Which gluconeogenesis enzyme requires biotin?
Pyruvate -----> Oxaloacetate
When does insulin level peak after an injection?
Peaks at 4 hours and is absent after 8 hours
After 12 hours of not eating describe the body's metabolic state
We will be in Glycogenolysis because the liver glycogen stores will not yet be depleated.
Glucagon will be circulating and levels of cAMP and PKA will be elevated phosphorylating glycogen synthase (inactivating it) phosphorylase kinase (activating it) and glycogen phosphorylase (activating it)
What are the two unique steps of the glyoxylate cycle?
Give an example of a futile cycle
After the pyruvate carboxylase and PEPCK reactions if Pyruvate kinase is not inactivated the PEP will be turned into pyruvate and form a futile cycle.
Presence of glucagon will increase cAMP and cause the phosphorylation of Pyruvate kinase inactivating it to prevent this shit show
What inhibits PFK-1
Low levels of F23BP, presence of ATP and Citrate
What inhibits pyruvate dehydrogenase?
Acetyl CoA from FA oxidation
Caffine inhibits cAMP phosphodiestrase. If caffine and glucagon are administered together what will be the result?
A large increase in cAMP with no way to degrade it. This will initiate the Gluconeogenesis cascade
Pyruvate Kinase will be phosphorylated and inhibited
Glycogen synthase will the +Pi and inhibited
Phosphorylase Kinase will be +Pi and activated
Glycogen Phosphorylase will be +Pi and activated.
After an overnight fast the patient has glycogen in the urine with short branches (4 units) what enzyme is defficent?
What if the branches were one glucose unit long?
4:4 Transferase is the debranching enzyme and its inhibition will leave 4 glucose unit branches on glycogen
If they were 1 glucose branches then 1:6 Glucosidase would be inhibited
What is the energy gain from dietary carbs versus carbs generated from glycogen stores In anaerobic conditions
In anaerobic conditions we are creating lactate
2 ATP from Pyruvate to Lactate
Remember when glycogen is broken down to glucose 1 Phosphate you do not need Hexokinase to begin glycolysis so you will invest one less ATP to utilize glycogen.
What causes F23BP release from the liver?
F23BP's objective is to cause glycolysis in the liver for the synthesis of FA. So high blood glucose will cause its release. Glucagon and Epinephrine will inhibit its release.
What are the 4 different pyruvate metabolic pathways
1. (Alanine) carries amino groups to the liver from muscle
2. (Oxaloacetate) can replenish TCA cycle or be used for gluconeogenesis
3. (Acetyl CoA) Transition from glycolysis to the TCA cycle
4. (Lactate) End of anaerobic glycolysis
Which ONE of the following statements about the third of the three stages involved in the extraction of energy from foodstuffs is correct?
A. It involves the breakdown of fuel molecules into smaller units such as amino acids, fatty acids and glucose
B. It involves the degradation of amino acids, fatty acids and sugar into a few common metabolites.
C. It releases comparatively little energy compared to the first and the second stages of catabolism.
D. It is common to the oxidation of all fuel molecules and produces most of the ATP and CO2 in cells.
E. It is a major source of reducing equivalents during anaerobic respiration.
Compartmentation of the reactions of anabolic and catabolic pathways:
A. prevents them from occurring simultaneously.
B. forces the reactions in these pathways to occur even if the metabolic intermediates are lacking.
C. precludes the utilization of metabolic intermediates from other metabolic pathways.
D. minimizes the operation of a substrate cycle and the wasteful expenditure of energy.
E. permits a cell to switch easily from the anabolic mode to the catabolic mode and vice versa.
In the regulation of metabolic pathways, which of the following reactions is most likely to be modulated by allosteric effectors?
A. The fastest reaction in the pathway.
B. The first reversible reaction in the pathway.
C. The initial reaction of the pathway.
D. The reaction which synthesizes the final product of the pathway.
E. The reaction which follows a branch point in the pathway.
The biochemical pathway for the catabolism of a molecule is almost never the same as the pathway for the biosynthesis of that molecule because:
A. enzyme-catalyzed reactions are usually irreversible.
B. biochemical systems are usually at equilibrium.
C. catabolic and anabolic reactions seldom take place in the same cell.
D. metabolic intermediates are specific for either catabolic or anabolic pathways, but not both pathways.
E. the regulation of the pathway would be extremely difficult if it served both functions.
A regulatory cascade results in:
A. the operation of a substrate cycle.
B. an increase in the energy charge of a cell.
C. the amplification of a metabolic signal.
D. a cell switching from catabolism to anabolism.
E. an increase in the storage of fuel molecules in tissues.
Which of the following represents the reversible covalent modification of an enzyme?
A. allosteric modification
B. change in enzyme activity with pH
C. competitive inhibition
D. phosphorylation (of the side chain of serine)
E. proenzyme (zymogen) activation
The generation of metabolic energy from glucose requires a pathway known as glycolysis. Based on the principles of metabolic regulation, the most likely mechanism of regulation for this pathway is inhibition of the:
A. first irreversible step by glucose.
B. last irreversible step by ADP.
C. first irreversible step by ADP.
D. last irreversible stp by ATP.
E. first irreversible step by ATP.
Consider a typical metabolic pathway in which the rate of utilization of the substrate of the first enzyme in the pathway is regulated by the product of the last enzyme in the pathway. Which of the following statements is least likely to be correct for this pathway?
A. The first enzyme in the pathway shows cooperativity.
B. The last enzyme in the pathway obeys Michaelis-Menten kinetics.
C. All of the enzymes in the pathway are allosteric enzymes.
D. The product of the final enzyme reaction is a negative regulator of the first enzyme in the pathway.
E. Overall, an unfavorable reaction is made to occur by coupling it to a favorable reaction.
Each of the following statements about the energy charge of a cell is correct except:
A. It has a value ranging from zero to one.
B. It is buffered in that its value is maintained within rather narrow limits.
C. A high energy charge stimulates ATP-generating pathways.
D. A low energy charge inhibits ATP-utilizing pathways.
Listed below are a group of metabolic pathways (or reactions) and their subcellular location. Which one of the paired items is INCORRECT?
A. lactate dehydrogenase - cytosol
B. phosphogluconate pathway - cytosol
C. glycogenolysis - mitochondria
D. pyruvate carboxylase - mitochondria
Which of the following metabolic intermediates is considered to be a high energy compound?
A, D, and E are correct
The ATP/ADP cycle plays a central role in cellular metabolism and the oxidation of food. Which ONE of the following statements about the ATP/ADP cycle is INCORRECT?
A. The ATP/ADP cycle involved in the oxidation of carbohydrates and fats.
B. Energy-requiring reactions in cells only occur when ATP is being synthesized from ADP.
C. ATP provides energy that drives the energy-utilizing processes in the cell.
D. The formation of most of the ATP in cells is coupled to the reduction of oxygen.
E. The complete oxidation of carbohydrate, protein, and fat results in the formation of CO2.
The pyruvate dehydrogenase complex has three enzymes. What essential role does the E3 subunit (dihdrolipoyl dehydrogenase) serve in PDH function?
Takes high energy electrons off FADH2 and transfers them to NADH
There are several branchpoints in the TCA cycle where intermediates can be used for more than one purpose. Pick one intermediate and tell what another use is for that intermediate.
Citrate is the most important one. This molecule inhigits PFK-1 in glycolysis thus halting the cycle and is necessary for FA synthesis.
A-Ketoglutarate can be converted to glycerol and used for amino acid synthesis.
Odd chain fatty acids can be shunted into the system through Propaniol CoA in the conversion through Succinyl CoA.
What are the two important steps that are missing in the glyoxylate cycle compared to the TCA cycle? Why does that make the glyoxylate cycle so useful for the organisms that have it?
What happens to the electrons removed from acetyl-CoA in the TCA cycle?
What molecules do they end up on?
They End up reducing O2 to H20 in the electron transport chain and generating a proton gradient that drives ATP synthesis.
How is the oxidation reduction potential (redox potential) related to how electrons flow in the electron transport complexes?
NADH and FADH2 have a very Negative reduction potential
There are four flavoproteins that we discussed in the lecture on electron transport. What molecule receives electrons from all four flavoproteins?
How many Protons are pumped per pair of e-
Succinate Q Reductase
Electron Transfer Flavoprotein Dehydrogenase
4sn-Glycerol Phosphate Dehydrogenase
10H+ when the e- enter at NADH-Q Oxidoreductase
6H+ when the e- enter at Succinate Q Oxidoreducatse
Peter Mitchell predicted the Q-cycle of the bc1 complex (complex III). In the Q-cycle, only one of the ubiquinone electrons goes on to reduce oxygen at complex IV. Where does the second electron go?
It gets transferred to Cytochrome b1 then gets returned to the Q pool
Incomplete reduction of oxygen at cytochrome c oxidase (complex IV) can produce toxic reactive oxygen species (ROS). Name one of these partially reduced oxygen species and describe why it is dangerous.
Superoxide is converted to hydrogen peroxide, which is less toxic. If superoxide dismutase is deffective you get Lou Gehrigs disease
The E2 subunit of pyruvate dehydrogenase complex has lipoic acid as a cofactor. What does the lipoic acid do in the complex?
The alpha-ketoglutarate dehydrogenase complex decarboxylates a five carbon alpha-keto acid to form a four carbon CoA product, succinyl-CoA. What other complex that we studied does a similar reaction?
The TCA cycle has two decarboxylation steps that remove two carbons as CO2 for every acetyl-CoA that enters the pathway. Acetyl-CoA is the product made by oxidizing fatty acids. What is the metabolic consequence/result of these decarboxylation steps for humans? How do plants, bacteria and fungi get around this problem?
In Haemophilus influenza, three enzymes (citrate synthase, aconitase and isocitrate dehydrogenase) are missing. How does that explain the need for high concentrations of glutamate in the media for growing this bacterium?
How does the 110 angstrom long helix HL help to explain the mechanism of proton pumping in complex I?
What is the role of ubiquinone in electron transport?
In the Q cycle in complex III, what eventually happens to the ubiquinone that binds to the n-center (near the matrix)? You may want to say what happens at the n-center in the first part of the Q-cycle and then the second part of the Q cycle.
Cytochrome c oxidase (complex IV) is the enzyme that reduces oxygen to water. If this process is incomplete, reactive oxygen species (ROS) may be released into the mitochondrial environment. How does the mitochondria protect itself from these ROS?
If you could engineer disulfide bonds between all the Fo c subunits so they made a covalently connected ring, would this stop ATP synthesis? Why or why not?
If a drug could be found that could activate uncoupling protein 2 (UCP2) to reduce the proton gradient by 5%, would this be a good drug to induce weight loss? Why or why not?
The binding change mechanism says that the three beta subunit structures are interconvertible. What interconverts them to make the ATP synthesis work?
What keeps the F1 ball of the ATP synthase from turning when the gamma subunit turns?