Question

or perform normal tasks because she became rapidly fatigued. She was 5 feet 4 inches tall,

and weighed only 82 pounds although her daily calorie intake was 3,000 to 3,500 calories. Her

intestinal function and absorption appeared normal. Her blood glucose, blood CO

2

, and red

blood cell counts were normal, but her breathing rate and heart rate were increased. On

average, her temperature was elevated a degree. She drank large amounts of water and

perspired profusely with no increase in urine output.

The combination of her caloric intake, her abnormally low level of physical exertion and her low

body mass led the physicians to test her basal metabolism. Her fasting, resting basal metabolic

rate (BMR) was 3 times normal. BMR is determined by oxygen consumption measured over a

period of time and represents energy used for housekeeping functions of tissues and organs

under basal conditions.

A muscle biopsy was taken from the patient and her mitochondria were isolated to determine

how many moles of ATP were formed per atom (1/2 mole) of oxygen consumed. This is called

the P/O ratio. Simply, this assay involves putting mitochondria in a buffer containing ADP, Pi,

TCA substrates and other reagents. The results are shown below.

Saturating [ADP]

	substrate	P/O
Control	pyruvate-malate	3.0
Control	alpha-ketoglutarate	2.7
Patient	pyruvate-malate	2.6
Patient	alpha-ketoglutarate	2.4

The assay from above was repeated using low levels of ADP (not saturating as above). In control mitochondria, oxygen consumption was extremely low. However, in the patient’s mitochondria, the oxygen consumption was similar to that in the presence of ADP, indicating a high rate of electron transport in when ADP levels are low.

Low [ADP]

	substrate	P/O
Control	pyruvate-malate	0.2
Control	alpha-ketoglutarate	0.1
Patient	pyruvate-malate	2.7
Patient	alpha-ketoglutarate	2.5

6. Since the P/O ratio is near normal in the presence of ADP, where is the proton leak likely

occurring? Explain your reasoning.

7. When ADP levels are low, how does flux through glycolysis and the TCA cycle differ in the

patient and the control? (in other words, how is glycolytic and TCA enzyme activity changed and

how does it happen?) Explain your reasoning.

8. How does this defect affect the patient’s food intake, body weight, body temperature, and

water intake?

Answer 1

Q.6.Proton leak is across the mitochondrial membrane, and there is synthesis of ATP. This will increase oxygen consumption. It is dissipation of P in presence of ATP synthase.

Q.7. Glycolytic and TCA cycle changed its all because of the availablity of Decrease in oxygen level. The major source of Glycolytic pathway is energy, from which 2 ATP and 2 pyruvate.

The citric acid is regulated by ATP and NADH concentration. The enzymes isocitrate dehydrogenase, and Alpha- ketoglutarate dehydrogenase, stimulate ADP.

2 ATP produced in glycolysis and krebs cycle 1ATP .

Phosphofructokinase enzyme control Glycolysis in control element in mammal for Glycolytic pathway.it lowers affinity for fructose6 phosphate.there is prevention of formation of Lactic acid, by inhibition of phosphofructokinase.

Both inside and outside of the cell Glycolytic pathway Flux is adjusted . There is two major cellular needs:- 1. There is degradation of glucose by ATP production. 2. Formation of Fatty acids.

There must be irreversible reaction , and the reaction is controlled by hexokinase, pyruvate kinase, phosphofructokinase.

Q.8. Body weight is reduced by using sodium/ glucose co-transporter .

The use of canagliflozin, dapagliflozin, reduced risk of heart failure, cardiovascular death.

There is production of heat , when energy is dissipated.