Glycolysis Flashcards
describe the general glucose uptake by cells.
adipose and muscle are insulin dependent but rest are not
compare hexokinase and glucokinase
glucokinase - liver and pancreatic beta cells
hexokinase - all others
Km for glucokinase is much greater
Vmax for glucokinase is higher
hexokinase is inhibited by glucose 6 phosphate
insulin induces glucokinase
hexokinase in brain and RBCs always saturated, whereas pancreas and liver can sense changes
describe the role of glycolysis in different tissues
muscle: supply energy for muscle contraction
liver: glucose converted to fat or glycogen for storage in fed state, in fasted state, reversible reactions used for gluconeogenesis
RBC: derives all its ATP
Brain: glucose is primary fuel
Describe the regulation of glycolysis
availability of substrate: glucose, ADP, Pi, and NAD+
more anaerobic conditions, greater dependence on glycolysis for energy
regulatory enzymes: phosphofructokinase-1, pyruvate kinase
What is the purpose of galactose synthesis from glucose?
galactose needed for synthesis of glycoproteins and glycolipids in membranes and proteoglycans in extracellular matrix. UDP-galactose used by galactotransferase. In lactating mammary gland, UDPgalactose used for lactose synthesis. Specificity for galactotransferase is modified by alpha-lactalbumin, so D-glucose can be used as acceptor molecule to form lactose.
What are the consequences of high fructose intake?
enhanced fatty acid,triglyceride and VLDL synthesis by liver. Fructose is metabolized by liver more rapidly than glucose, because it bypasses the rate-limiting step. Metabolism is insulin independent. Can cause liver damage
What conditions promote the conversion of pyruvate to alanine?
a defect in either of hte major pathways of pyruvate utilization (conversion of acetyl coA to oxaloacetate which leads to accumulation of lactate and alanine
what are the functions of the pentose phosphate pathway?
major source of NADPH for biosynthetic reactions
Major source of ribose 5-P for nucleotide synthesis
Recycling of excess pentose phosphates back to glyceraldehyde 3-phosphate and glycolysis. (important in RBCs especially)
Describe the tissue distribution of the pentose phosphate pathway
Pathway is ubiquitous and enzymes are localized in the cytosol. Pathway especially active where cytochrome P45-dependent hydroxylation reactions occur and where fatty acids, cholesterol, bile acids, and steroid hormone synthesis occurs (liver and adrenal glands). RBCs and phagocytic cells have special requirement for NADPH, and are enriched in pentose phosphate pathway enzymes
Describe the two pathways of the pentose phosphate pathway
oxidative branch (irreversible): functions to generate NADPH and pentoses Non- oxidative branch (reversible): recycles excess pentose phosphates. It interconverts C6, C5, and C3 monosaccharides. The pentose phosphate pathway and glycolysis share: fructose 6 phosphate and glyceraldehyde 3 phosphate. When the need for NADPH is greater than need for pentoses, non oxidative phase allows excess pentose phosphates to be converted to glycolytic intermediates
Describe the effect of antimalarial drugs in people with G6P DH
antimalarial drugs precipitate oxidative stress by increasing the production fo toxic oxygen metabolites. In normal people, ROS are reduced in reactions requiring NADPH. In individuals deficient in glu-6-p DH, there may be an inadequate supply of NADPH, and anemia may occur if person is taking an antimalarial drug
Which vitamins have antioxidant activity?
Vitamin E, beta-carotene (Vitamin A precursosr) and Vit C can reduce toxic ROS to non-toxic products
Explain the effects of ROS in killing microbes and general effects
ROS trigger ionic flux across membrane of phagocytic vacuoles, creating a hypertonic environment and elevated pH, which result in release and activation of proteases that attack the phagocytized microbe
Effects can be prevented by Vitamin E.
There are single strand breaks in DNA
Depolymerization of proteoglycans in connective tissue
Peroxidation of membrane lipid
Source of precursors for other biosynthetic pathways.
succinyl COA --> heme synthesis oxaloacetate --> glucose synthesis citrate --> fatty acid synthesis alpha ketoacids --> nonessential aminoa acid synthesis malate --> gluconeogenesis
What is the overall reaction for the citric acid cycle?
acetyl CoA + 3NAD+ + FAD –> GDP + Pi + 2H2O –> 2CO2 + 3NADH + FADH2 + GTP + 2h+ + CoASH
What is the role of vitamins, coenzymes in the TCA
niacin = NAD
thiamin (vit B1) = TPP = decarboxylation of alpha-keto acids
riboflavin = (Vit B2) = FAD, FMN
pantothenic acid = CoASH = activation of acyl groups
lipoic acid = lipoamide = carrier of electrons and acyl groups
Describe respiratory control in the TCA cycle
oxygen is required for cycle to run because TCA is tightly couples to ETC. Therefore electron carriers cannot be regenerated without the presence of oxygen
the rate of the cycle is dependent on the supply of oxidized cofactors (NAD+ and FAD) which are dependent on availablity of O2 and ADP
What are the anapleurotic reactions?
these reactions replenish TCA intermediates
pyruvate carboxylase reaction - the major reaction: pyruvate –> OAA
trasaminase reactions: pyruvate + aspartate –> alanine + OAA
pyruvate + glutamate –> alanine + alpha ketoglutarate
malic enzyme reaction: pyruvate –> malate
describe the hypoglycemia (fatal, neonatal and alcoholic)
fasting - overnight fast –> gluconeogenesis
neonatal –> within first few hours neonates start carrying out gluconeogenesis
alcoholic –> consumption of a large amount of ethanol depletes pyruvate. oxidation of alcohol produces large amounts of NADH. The electrons transferred from pyruvate to lactate to restore and regenerate NAD+
What tissues carry out gluconeogenesis?
liver and kidney
Describe the cori cycle
it is an interorgan cycle that operates between the liver and either the rbc or anaerobic skeletal muscle
lactate made in skeletal muscle or RBC can be extracted by liver and used for gluconeogenesis
enzyme: LDH
no net glucose synthesis
What are the gluconeogenic amino acids?
give rise to intermediates in glycolysis or TCA
all amino acids, except leucine and lysine
major glucogenic amino acids: alanine
Describe the alanine cycle.
interorgan xycle that operates between liver and skeletal muscle. Skeletal muscle derived from glucose, acts as an acceptor for amino groups from many of the individual amino acids. Alanine carries the amino group from muscle to liver, where they can be incorporated into urea for excretion. When alanine is in the liver it is reconverted to pyruvate.
This cycle is important because free ammonia is extremely toxic and most detox occurs in liver where it is converted to urea
where does the gluconeogenic pathway take place?
the first step where oxaloacetate is converted to oxaloacetate is done in the mitochondria, but the other steps occur in the cytosol.
Where does the energy for gluconeogenesis come from?
fatty acid oxidation
Describe the malate-oxaloacetate shuttle
oxaloacetat is impermeable to the inner mitochondrial membrane. so it is converted to malate to leave mitochondria.
Describe the energy requirements of concerting OAA to PEP
atp used in pyruvate carboxylase reaction
gtp used in PEPCK reaction
Describe the regulation of the glucogenic pathway
its repressed after carb feeding, induced in starvation, stress and diabetes
covalent modification is induced by glucagon and mediated by cAMP-dependent protein kinase
two enzymes are phosphorylated: pyruvate kinase and bifunctional enzyme
pyruvate kinase: activity decreased by phosphorylation: slows conversion of PEP to pyruvate, more PEP for gluconeogenesis
bifunctional enzyme: 2phosphatase is activated when phosphorylated, level of fructose 2,6 bisphosphate decreased, increasing FBPase 1 activity and decrease in PFK1
