Glycolysis Flashcards
Types of regulation
Thermodynamic (substrates inc NAD:NADH, ATP:ADP)
Kinetic (allostery, phos)
Hormonal (usu via kinetic, genetic)
Genetic (long term, transcription, expression)
Monosaccharides
Pentose - ribose, deoxyribose Hexose - glucose - mannose - galactose - fructose
Have transporters in epithelium of small intestine
Most cyclic in solution (aldehyde less reactive)
Disaccharides
- sucrose = glu a1-b2 fruc
- lactose = galac b1-a4 glu
- maltose = glu a1-a4 glu
Need enzymes in brush border for absorption
Polysaccharides
Cellulose = glu b1-4 glu - we can't break down Starch = glu a1-4 glu - need alpha-amylase Glycogen = glu a-4 glu with a1-6 branches - need amylase, isomaltase
Reducing sugars
“Benedict’s test”
Terminal aldehyde reduces cuprous citrate -> red
Also glycosylate amines of proteins (ex A1c in diabetes)
Glucose Galactose Lactose Maltose Fructose - only in aldehyde vs ketone isomer
Lactose intolerance
Usu acquired -> >50% of adults
No lactase -> lactose to colon -> fuel source for bacteria -> H2 gas, acetaldehyde, EtOH, toxins
Dx with H2 gas in breath, hyperglycemia from lactose
Glucose transport
Facilitated diffusion (reversible, driven by gradient) Regulated by expression and sequestration
ex GLUT 4 muscles, adipose = insulin dep
GLUT 1 RBCs = constitutive
Hexokinase
Glucose + ATP -> G6P + ADP
Irreversible, G6P now trapped
Low Km -> active at low concentrations
Direct inhibition by G6P
Glucokinase -
High Km -> predominant at high concentration
- liver -> metabolism
- pancreas -> insulin release
Glycolysis overview
Anaerobic - used in every cell
(exclusive in RBC bc no mitochondria)
Glucose + 2 ADP + 2P -> 2 Lactate + 2 ATP
requires input of 2 ATP -> net yield of 2
PFK1
Phospho-fructo-kinase 1
Fructose6P + ATP Fru1,6BisP + ADP
Allosteric regulation
(+) AMP, Fruc 2,6 bisP
(AMP from adenylyl kinase: 2 ADP -> ATP + AMP) (-) ATP, citrate
PFK2
Indirect regulator of PFK1
(Fruc2,6bisP stimulates PFK1
Bi-functional enzyme:
Fruc1P + ATP Fruc2,6bisP + ADP
(+) dephosphorylated -> PFK2 active
(+) insulin via protein phosphatase
(-) phosphorylated -> bisphos 2 active (reverse)
(-) glucagon via PKA
Pyruvate kinase
Phosphoenol purvate + ADP -> pyruvate + ATP
(final step of glycolysis)
(+) Fruc 1,6 bisP
(+) phosphorylation (hormonal)
(-) ATP
(-) cancer - expresses slower PKM-2
Lactate dehydrogenase
Pyruvate + NADH -> lactate + NAD+
(regenerates NAD+, lactate transported out for continued glycolysis)
Reversible:
(+) NADH
(-) lactate
Isoenzymes:
(+) M (muscle) -> forward
(-) H (heart, liver) -> captures lactate
Pentose phos pathway
Alternative for G6P
- makes ribose 5-P for nucleotides
- energy from 5-C sugars
- regenerates NADPH (necessary to detox reactive O2 species, ie via glutathione)
Glucose6P dehydrogenase
First step of pentose pathway
Necessary for oxidative stress (via glutathione)
- esp RBCs, no other source of NADPH
(+) NaDP+