glycolysis and TCA Flashcards
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
all true
—- a common disorder caused by the disregualtion of glucose metabolism
diabetes
glycolysis is the pathway that converts —- to —- which is the metabolic precursor of —-
- glucose
- pyruvate
- acetyl coA
the map of metabolism :
- glucose ( 6 carbon ) —> 2x pyruvate ( 3 carbon ) this step is glycolysis by which only one glucose gives 2 pyruvate
- 2 pyruvate —> NADH , ATP generated , 2x acetyl coA carbon 2 ( done by pyruvate dehydrogenase )
- 2 x c leaves the TCA cycle as C02 NADH FADH2 and GTP generated , this is the TCA cycle
key enzyme reactions in energy generating pathways:
redox reactions catalysed by —– many are reversible reactions generate ——–
- dehydrogenase
- NADH , FADH2 , NADPH
substrate level phosphorylation reaction catalysed by —- some reversible , generate —
- kinases
- GTP , ATP
key mechanism regulating energy generating pathway:
- usually a rate limiting step in biochemical pathways
- feedback and allometric regulation of enzyme activity
such as:
- NADH can inhibit enzymes leading to its production
- NAD+ can stimulate - hormonal regulation as:
- insulin regulates glucose uptake to cells which increases GLUT4 - activation and inactivation of enzymes by phosphorylation/dephosphorlation
- 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
glucose enters most cell types by —— mediated by —– also —–
- facilitated diffusion mediated by GLUT protein
- sodium dependent co transport SLGT protein
there are at least —- GLUT proteins transporters —– which differ in their tissue specific expression eg. ——adipose and skeletal tissue
- 14
-isoforms - GLUT4
once inside the cell the glucose is —- by phosplhaton and the are no cell membrane transport systems for phosphorylated sugars
trapped
- glucose is converted to glucose-6-phosphate by —– which is most cell types of —- found in liver parachemyl cells and pancreatic islet cells
- hexokinase
- glucokinase
-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
- b cells
- rise
- insulin
- liver
- high
- minimizes
- glycogen
- capacity
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
- low
- high
- low
- limited
( check slide 9 )
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
-02
-anarobic
-lactic acid
- oxidative phsophorlation
- atp sytehsis
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
- muscles
- lactic. acidosis
—– is the rate limiting step of glycolysis and the activity is highly regulated
phosphofructokinase 1 ( PFK1)
feedback and allometric inhibition :
the PFK1 is inhibited by —-
the glucokinase is inhibited by —- substrate —-
- atp
- PFK1 susbatre fructose-6-phosphate
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 )
- fructose-2,6 biphosphate
- fructose6-phosphate
- PFK2
- fructose-2,6 biphosphate
- insulin
-PFK1
-glucogenogensis
( check slide 13 +14 important )
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 ——
- cytosol
- pyruvate transporter
- mitochondrion
PDH is a —– complex of —- enzymes and —- coenzymes which are;
- multi enzymes
- 3
- 5
- NAD+ , FAD , TPP , Lipoic acid , coA
an — reaction when glucose can’t be made from —– as its allosterically inhibited by —–
the activity is also controlled ——-
- irreversible
- acetyl coA
- Acetyl coA and NADH
- ATP: ADP ratio high atp inhibits , low atp activates
( check slide 16 )
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:
- 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
energies of TCA cycle:
- 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
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
- NADH , FADH2 , GTP
- metabolic
- acetyl coA
- amphilatic
- anabolic and catabolic
