Metabolism I Flashcards
What are converted to high energy ATPs to provide energy for cells and tissues?
- glucose
- FA
- AA
Sources of ATP
- Adenylate kinase
- Creatine phosphokinase/phosphocreatine (CPK)
- Anaerobic metabolism
- Aerobic metabolism
Glycolysis
breakdown of 1 molecule of glucose (6C) into 2 molecules of pyruvate (3C)
Where does glycolysis occur?
Cytoplasm
How many steps are there in glycolysis?
10 steps
Major points in glycolysis
glucose –> C6P –> pyruvate –> acetyl CoA
Three enzymes of glycolysis
- hexokinase (HK)
- PFK
- PK
Where does pyruvate go after glycolysis
- Lactate (PDH pathway)
- acetyl CoA –> TCA cycle (PDH pathway)
How many stages is glycolysis broken into?
3
Where does the formation of acetyl CoA occur?
mitochondria
What enzyme is responsible for pyruvate conversion to acetyl CoA?
Pyruvate dehydrogenase complex
How many ATP are generated when converting pyruvate into acetyl CoA?
2 ATP
Where does the Kreb’s cycle occur?
Mitochondria
What does the Kreb’s cycle depend on?
availability of substrates and cofactors
How many ATP molecules are produced from glucose by aerobic respiration?
36 ATP
What is the net energy of ATP from glycolysis?
2 ATP
What is the net energy of ATP from Kreb’s cycle
32 ATP
What regulates glycolysis?
- Hexokinase
- Glucokinase
How many isoforms of hexokinase are present?
4
I, II, III and IV
What is HK IV called?
glucokinase
Where are HK I - III found?
in most tissues
HK I - III Km
Low Km for glucose relative to its concentration in blood
What is HK I - III inhibited by?
Strongly inhibited by G6P
Where is HK IV found?
liver and pancreas
HK IV and Km
high KM for glucose
HK IV inhibition
less sensitive to inhibition by G6P
What is glucokinase regulated by?
- F6P
- fructose
GK inhibitory protein
- GK-RP
- sequesters GK as an inactive complex in nucleus
Where is GK-RP found?
nucleus of liver cells
What promotes the binding of GK to GK-RP?
F6P
What inhibits GK?
F6P
How is F6P inhibition of GK overcome?
by large increase in glucose concentration
Fructose and GK
- fruits
- vegetables
- high fructose corn syrup
What does fructose get converted to?
F1P
What activates GK?
F1P
Role of F1P
- promotes hepatic glucose utilization
- partly responsible for adverse effects of fructose consumption (lipogenesis, hypertriglyceridemia etc)
GK as an enzyme
inducible
What stimulates GK transcription?
Insulin
What can a mutation in GK lead to?
a form of MODY
What does PFK1 catalyze?
the first committed step in glycolysis
What are the negative effectors of PFK1?
ATP
Low pH
Citrate
What are the positive effectors of PFK1?
AMP (cAMP)
F2,6BP
What inhibits PFK1?
ATP (negative allosteric effector)
What promotes PFK1 activity?
AMP (positive allosteric effector)
What does F1,6 BP’ase catalyze?
an irreversible reaction opposite to that catalyzed by PFK1
What doe PFK1 and F1-6BP’ase together catalyze?
futile cycle
What inhibits F1,6 P’ase?
AMP
What does the inhibition of F1,6 P’ase lead to?
- increased F1, 6BP
- glycolytic flux
What is PFK1 regulated by?
- intracellular pH
- citrate
- H + ions
What is PFK1 not regulated by?
Lactic acid (the end product of glycolysis)
What do some tissues prefer as fuels instead of glucose?
FA and ketone bodies
Why do some tissues prefer FA and ketone bodies over glucose?
to spare glucose for use by organs which specifically require glucose for energy (brain)
What does citrate inhibit?
PFK1
- thus glucose utilization
Where does citrate accumulate?
in cytosol
What inhibits glycolysis?
Glycogen
Epinephrine
What is a positive allosteric effector of PFK1?
F2,6P
What happens if there if no F2, 6P?
glycolysis cannot occur in liver
What triggers adenylate cyclase through cAMP?
binding of glucagon to its receptor triggers
What does adenylate cyclase through cAMP cause?
decrease in F2, 6P
What does a decrease in F2, 6P lead to?
- reduces PFK1
- activates F1, 6BPase
- inhibit glycolysis
F1, 6P and glycolysis
intermediate via PFK1
F2, 6P and glycolysis
side product via PFK2
What does F2,6BPase oppose?
PFK2 bi-functional enzyme - same protein
What inactivates kinase?
Phosphorylation
What activates phosphatase activity?
phosphorylation
What activates kinase?
dephosphorylation
What inactivates phosphatase activity?
dephosphorylation
What regulates glycolysis?
- PK
What inhibits PK?
physiological concentration of ATP
What activates PK?
F1, 6BP
Is PK active or inactive in the phosphorylated state?
inactive
Is PK active or inactive in the dephosphorylated state?
active
What causes a change in activity of PK?
covalent modification by PKA
What is PK induced by?
- high carbohydrate intake
- high insulin levels
- in liver
Glycogen synthase
- converts glucose to glycogen
- insulin promotes glycogen synthesis
- fed state
Glycogen phosphorylase
- breakdown glycogen to glucose
- glucagon promotes glycogen breakdown
- fasted state
When is glycogen synthase active?
fed state
When is glycogen phosphorylase active?
fasted state
Gluconeogenesis
formation of new sugar
When is gluconeogeneis activated?
- fasting condition
- during exercise
What promotes gluconeogenesis?
Glucagon to protect against hypoglycemia
What does gluconeogenesis provide glucose for?
brain
muscles
erythrocytes
Where does gluconeogenesis take place?
- mainly in liver
- small extent renal cortex
What are the precursors for gluconeogensis?
- pyruvate
- lactate
- glycerol
- certain AA (alanine, aspartate)
When is the Cori cycle active?
after exercise
Cori cycle
muscles get glucose from stored glycogen
What is glucose converted to in the Cori cycle?
lactic acid
What happens to the lactic acid in the Cori
redirected to liver for gluconeogensis
Where is the glucose released in the Cori cycle?
into blood
Where is glucose taken up in the Cori cycle?
- muscle
- used for energy and stored as glycogen
