glycolysis and TCA

Question 1

true or false:
-glucose and related sugars are important components of our diet eg. breakdown product of carbs such as starch
- the Boyd has to maintain constant glucose levels in circulation
- some tissues can only use glucose as a metabolic fuel as: brain erythrocytes renal medulla cornea testes excersising muscle

Answer 1

all true

Question 2

—- a common disorder caused by the disregualtion of glucose metabolism

Answer 2

diabetes

Question 3

glycolysis is the pathway that converts —- to —- which is the metabolic precursor of —-

Answer 3

• glucose
• pyruvate
• acetyl coA

Question 4

the map of metabolism :

Answer 4

1. glucose ( 6 carbon ) —> 2x pyruvate ( 3 carbon ) this step is glycolysis by which only one glucose gives 2 pyruvate
2. 2 pyruvate —> NADH , ATP generated , 2x acetyl coA carbon 2 ( done by pyruvate dehydrogenase )
3. 2 x c leaves the TCA cycle as C02 NADH FADH2 and GTP generated , this is the TCA cycle

Question 5

key enzyme reactions in energy generating pathways:
redox reactions catalysed by —– many are reversible reactions generate ——–

Answer 5

• dehydrogenase
• NADH , FADH2 , NADPH

Question 6

substrate level phosphorylation reaction catalysed by —- some reversible , generate —

Answer 6

• kinases
• GTP , ATP

Question 7

key mechanism regulating energy generating pathway:

Answer 7

1. usually a rate limiting step in biochemical pathways
2. feedback and allometric regulation of enzyme activity
   such as:
   - NADH can inhibit enzymes leading to its production
   - NAD+ can stimulate
3. hormonal regulation as:
   - insulin regulates glucose uptake to cells which increases GLUT4
4. activation and inactivation of enzymes by phosphorylation/dephosphorlation
5. avaliability of intermediate as:
   - availability of oxaloacetate affects the rate of citrate sythesis via citrate synthesis in TCA cycle
   - availability of oxygen by which oxygen is the finally acceptor of electrons entering the electron transpire chain from NADH/FADH2 generated during glycolysis and TCA cycle , hypoxia ( insuffiencet 02 ) or anoxia ( lack of 02 ) - failure of oxidative phosphorylation

Question 8

glucose enters most cell types by —— mediated by —– also —–

Answer 8

• facilitated diffusion mediated by GLUT protein
• sodium dependent co transport SLGT protein

Question 9

there are at least —- GLUT proteins transporters —– which differ in their tissue specific expression eg. ——adipose and skeletal tissue

Answer 9

• 14
  -isoforms
• GLUT4

Question 10

once inside the cell the glucose is —- by phosplhaton and the are no cell membrane transport systems for phosphorylated sugars

Answer 10

trapped

Question 11

1. glucose is converted to glucose-6-phosphate by —– which is most cell types of —- found in liver parachemyl cells and pancreatic islet cells

Answer 11

• hexokinase
• glucokinase

Question 12

-glucokinase helps — cells in the pancreas to sense —- of glucose concentration so it triggers —- release
- allows the —- to mop up the high concentration of glucose in the portal circulation after a meal
- high kn only kicks in at — concentration of glucose which —- the uptake of glucose by the liver during fasting so it prevents unnecessary synthesis of —- and the development of hypoglycaemia
- high kmax —> high —- allowing to handle the high glucose levels occurring post prandially

Answer 12

• b cells
• rise
• insulin
• liver
• high
• minimizes
• glycogen
• capacity

Question 13

hexokinase has — km which leads to — affinity for glucose even at — concentration , it allows glucose to enter the cell , specially cells in brain and rbc during fasting
- low kmax —> —- capacity

Answer 13

• low
• high
• low
• limited
  ( check slide 9 )

Question 14

lack of — promotes —- glycolysis resulting in —– synthesis from pyruvate , the end product of glycolysis instead of acetyl CoA ( which is formed under aerobic conditions ) , shuts down —– which results in reduction of —- sythesis

Answer 14

-02
-anarobic
-lactic acid
- oxidative phsophorlation
- atp sytehsis

Question 15

1.lactic acid accumulates in —- during vigours , extended exercise as cramp
2. —– refers to the elevated plasma levels of lactic acid secondary to > circulatory collapse ( MI,PE, haemorrhage ) > shock , and is potentially fatal

Answer 15

• muscles
• lactic. acidosis

Question 16

—– is the rate limiting step of glycolysis and the activity is highly regulated

Answer 16

phosphofructokinase 1 ( PFK1)

Question 17

feedback and allometric inhibition :
the PFK1 is inhibited by —-
the glucokinase is inhibited by —- substrate —-

Answer 17

• atp
• PFK1 susbatre fructose-6-phosphate

Question 18

hormonal regulation:
- PFK1 is activated by —— produced by PFK2 from —–
- insulin and glucagon control —- activity so it regulates the levels of —–
- F-2,6BP increases in response to —- after high carb meal , acting as the signal of high glucose increasing the rate of glycolysis by increasing —– activity
- F-2,6bp also inhibits —– to avoid unecessary synthesis of glucose ( one of the controls of blood glucose concentration )

Answer 18

• fructose-2,6 biphosphate
• fructose6-phosphate
• PFK2
• fructose-2,6 biphosphate
• insulin
  -PFK1
  -glucogenogensis
  ( check slide 13 +14 important )

Question 19

glycolysis occurs in —-
—– transports pyruvate into the matrix of mitochondrion when pyruvate dehydrogenase reaction takes place generating acetyl coA
TCA and electron transport chain are located in the ——

Answer 19

• cytosol
• pyruvate transporter
• mitochondrion

Question 20

PDH is a —– complex of —- enzymes and —- coenzymes which are;

Answer 20

• multi enzymes
• 3
• 5
• NAD+ , FAD , TPP , Lipoic acid , coA

Question 21

an — reaction when glucose can’t be made from —– as its allosterically inhibited by —–
the activity is also controlled ——-

Answer 21

• irreversible
• acetyl coA
• Acetyl coA and NADH
• ATP: ADP ratio high atp inhibits , low atp activates
  ( check slide 16 )

Question 22

the impaired activity of pyruvate dehydrogenase results in the inability to convert pyruvate to —– and therefore impaired tca activity and inability to make energy ( atp)
some diseases include:

Answer 22

• acetyl coA

[a] Pyruvate Dehydrogenase Deficiency
An inherited (X-linked) genetic defect which results in congenital lactic acidosis.
Pyruvate converted to Lactic-acid, NOT Acetyl-CoA
Symptoms:
- developmental defects (especially of the CNS)
- muscular spacticity
- early death
No effective therapy exists

[b] Arsenic poisoning
Arsenic inhibits enzymes that use lipoic-acid as a cofactor. Therefore, it will inhibit pyruvate dehydrogenase
Symptoms:
- neurological disturbances
Death
[c] Vitamin deficiencies
Coenzymes require vitamins for their synthesis:
CoA  Panthotenic acid (B5)
NAD  Niacin (B3)
FAD  Riboflavin (B2)
TPP  Thiamine (B1)

Deficiency in any of these vitamins impair pyruvate dehydrogenase function

Symptoms:
Pyruvate, lactate & alanine levels 
(pyruvate reduced to lactate or transaminated to alanine)
Severe lethargy & fatigue
Complications affecting the cardiovascular, nervous, muscular, & gastrointestinal systems

Question 23

energies of TCA cycle:

Answer 23

• 2C atoms enter the Cycle (as Acetyl-CoA) & leave as 2 x CO2

-One molecule of GTP is formed

-4 electron pairs are transferred during the Cycle,
three pairs to NAD+ & one pair to FAD

-Ultimately these will donate their electrons to the
Electron-transport Chain to make ATP

Question 24

in the TCA cycle:
-the energy is generated in the form of ——-
- the TCA cycle makes/provides poor of —– intermediates as: Oxaloacetate is used in Gluconeogenesis to make Glucose
- —– is aslo a substrate for biosynthetic reactions as:
synthesis of fatty acids, cholesterol &ketone bodies
- the TCA cycle is —- which means its involved in —- and —- pathway

Answer 24

• NADH , FADH2 , GTP
• metabolic
• acetyl coA
• amphilatic
• anabolic and catabolic