Biochemistry Flashcards
Adipose and muscle glucose transporter (more specific and highly regulated uptake of glucose, not basal)
GLUT4
Normal affinity - BG little higher than 5.6 mM
Insulin activates the assembling of GLUT4 at the membrane
Type 2 - defect in GLUT 4 assembly
Hexokinase and glucokinase
- where are they each found
- what’s hexokinase inhibited and activated by?
- function
- reversibility
- affinity to glucose
- Hexokinase in all cells, glucokinase in liver and pancreatic
- hexokinase inhibited by it’s own product G6P, and activated by insulin (similar with glucokinase)
- function to trap the glucose in the cell for glycolysis
- irreversible
- Hexokinase has high affinity and glucokinase has low affinity
PFK 1
- function
- regulation
- reversibility
- function of regulation tied to PFK2
Main control point, rate limiting step
- inhibited by ATP, citrate, low F-2,6-BP; activated by AMP, high F-2,6-BP
- insulin and glucagon indirectly affects PFK1 by directly affecting PFK2. PFK2’s product, F-2,6-BP regulates PFK1, the main control point. Purpose: to override the inhibition caused by ATP
Pyruvate Kinase
- function
- regulation
- reversibility
Production of ATP from PEP –> Pyruvate
Regulated by F-1,6-BP, a product from PFK1 reaction
Feed forward reaction, reaction depends on production of F-1,6-BP
Irreversible
Lactate dehydrogenase
- function
- regulation
- reversibility
Reduction of Pyruvate to lactate to oxidize NADH –> NAD+
Availability of O2
- reversible
DHAP
Fatty acid synthesis
Isomerization to G3P –> glycerol –> fatty acid
PEP and 1,3-BPG
High energy intermediates in glycolysis used to make ATP
Glycolysis in RBC
Mutase switches phosphate to another carbon.
Production of 2,3-BPG which reduces affinity of oxygen to HbA but not HbF (fetal), unloading oxygen to the tissues
2,3-BPG binds to the beta chains of HbA
Gal-1-P uridyltransferase
Epimerase that converts Gal-1-P to Glucose-1-P.
Diastereomer differing in one C
Fructose metabolism
Fructose broken down to DHAP and glyceraldehyde which are downstream from PFK1, the main control/rate limiting reaction, so fructose is a quick source of energy for both aerobic and anaerobic conditions
Pyruvate dehydrogenase
- Reduction of NAD+ to NADH, Pyruvate to AcetylcoA
- Inhibited by AcetylcoA, a lot of AcetylcoA then OAO for gluconeogenesis
- Irreversible: very very -∆G, spontaneous
- multi complex, many coenzymes like thiamine needed
- Activated by insulin in most tissues except for the nervous system
Indicated a well-fed state for storage into fatty acids
Glycogenesis
- enzymes involved
- how to add glucose
- regulation
- maximum rate
Glycogen synthase - rate limiting, extending 1,4-å chain.
Branching enzyme - hydrolysis a part of 1,4-chain then paste at 1,6-branch. Glycogen synthase works from there. Both working together reaches the maximum rate.
Glucose + UTP –> glucose-UDP –> added to glycogen
Positive feedback: G6P, insulin, ATP (a lot of energy -> build)
Negative feedback: epinephrine, glucagon, AMP (need glucose in the blood)
Glycogenolysis
- enzymes, rate limiting step
- how the enzymes debranch and release glucose
- positive and negative feedback
- Glycogen phosphorylase (alpha 1,4 dechain), and debranching enzyme.
- glycogen phosphorylase is rate limiting, a cycle based on demands
- debranching: remove the branch, reattach to the chain, and remove the last single 1,6-linkage glucose; a single glucose released
- positive feedback: AMP, epinephrine, glucagon
- negative feedback: ATP, insulin
How is G-6-phosphatase, an irreversible process in glycolysis made reversible back to glucose in glycogenolysis in the liver?
Depends on the location of G6Pase. G6Pase in the liver is in the lumen of ER so it’s reversible. Hexokinase in glycolysis in the cytoplasm is irrversible
Source of gluconeogenesis
Lactate
G3P (from TAG)
Glucogenic amino acids (all except lysine and leucine, alanine is a common glucogenic amino acid)
Gluconeogensis
- positive and negative feedback
- can fatty acids be converted to glucose?
- glucagon, epinephrine, ATP increase gluconeogenesis
- inhibited by insulin, and AMP
- mostly no, but only the odd number ones
Pyruvate to glucose
First converted to OAA in mitochondrial matrix to cross it.
Need malate-aspartate shuttle to cross to cytoplasm; converted to OAA then malate to use the shuttle
Activated by Pyruvate carboxylase (biotin) and inhibited by Pyruvate dehydrogenase (makes AcetylcoA).
Alanine and lactate conversion to glucose
First converted to Pyruvate then has to cross into mitochondria, then converted to OAA then malate to cross back out to cytoplasm through the malate-aspartate shuttle. Upon crossing, OAA becomes PEP to become G3P then on the path to become glucose.
Pyruvate to OAA in gluconeogenesis in the mitochondria
Inhibited by Pyruvate dehydrogenase (to make AcetylcoA)
Activated by biotin, Pyruvate carboxylase
AcetylcoA feedback on Pyruvate dehydrogenase and Pyruvate carboxylase (biotin)
Stop burning glucose; don’t go to CAC
Source comes from FA; FA burned for energy to stop the forward movement to CAC and allow gluconeogenesis in the liver. N
Positive on Pyruvate carboxylase and negative on Pyruvate dehydrogenase. Dehydrogenase wants to make AcetylcoA and Pyruvate carboxylase wants to convert Pyruvate to OAA –> malate –> shuttle to cytoplasm
PPP
- main products
- how different intermediates can be fed into and out of PPP
- 2 NADPH and ribose sugar –> nucleotide, RNA synthesis
- NADPH synthesis steps are irreversible.
- intermediates like G3P, F6P from glycolysis can enter and converted to 4, 5, 7- C sugars then to ribose-5-P by transaldolase and transketolases.
- reversible so glycolysis intermediates and PPP intermediates can go in and out of each other
Functions of NADPH
FA and cholesterol synthesis
Bleaching in WBC
Antioxidant - glutathione (reducing agent, reduce the free radicals)
Hepatic and pancreatic glucose transporter (more specific and highly regulated form of transport, not basal)
GLUT 2
Low affinity - needs excess glucose to be activated
Function is to uptake glucose for storage
B/c of low affinity, serves as a glucose sensor like G6K
