Week 2 Biochem Flashcards
rappaport-leubering Shunt
Happens only in mature erythrocytes.
It occurs in order to supply them with sufficient 2,3 BPG for unloading of oxygen under oxygen low conditions
accounts for 15-25% of all conversion to pyruvate
skips the atp producing step so produces less ATP, but the pay off for oxygen transport is worth this difference
ATP performs what functions in the RBC?
B. removal of intracellular potassium.
C. phosphorylation of glucose.
D. inhibition of pyruvate kinase.
E. removal of intracellular calcium.
A compensatory mechanism to allow adequate oxygen delivery to the tissues at high altitudes, where oxygen concentrations are low, would be which of the following?
increase in 2,3 BPG synthesis in the RBC
the net end products of glycolysis of 1 molecule of glucose are
(not including what happens after glycolysis)
- 2 ATP
- 2 NADH
- 2 Pyruvate molecules
how do you get from pyruvate to acetyl Co-A?
under anaerobic conditions pyruvate is converted to
Lactate
via lactate dehydrogenase (NADH is converted to NAD in the process)
exposure to which environmental toxin causes inhibition of GAPDH?
Arsenate/arsenic acid (H3AsO4)
in glycolisis, pyruvate kinase is used for?
removes the phosphate from the final intermediate PEP and converts it into pyruvate
excess lactate causes acidification of the muscles. what homeostatic process prevents this
lactate is transported to the liver where it enters the cori cycle where it is converted to pyruvate, then to glucose (gluconeogenesis) so that the glucose can be recycled back through the muscles or stored
3 fates of pyruvate
- conversion to lactate (regenerates NAD+ so that glycolysis can continue)
- conversion to alanine
- oxidation in mitochondria
hexokinase is inhibited by which glycolisis intermediate?
inhibited by its product: glucose 6 phosphate and by down stream product of rappaport-leubering shunt=2,6 BPG
protein Kinase A vs protein kinase C
- Protein Kinase C (PKC) is Ca2+-dependent (depends on IP3-mediated Ca2+ release!) and is activated by DAG (diacylglycerol). Mechanism of action: regulates the activity of various enzymes via phosphorylation of serine and threonine residues
-
Protein kinase A is ALSO a serine/threonine kinase but is activated by cAMP (cAMP leads to the release of catalytic subunits of PKA)
*
what type of cell signaling occurs to activate glycogenolysis
Example: Hypoglycemia → ↑ glucagon or adrenaline → GPCR activation → ↑ cAMP → activation of PKA:
→ Phosphorylation of glycogen phosphorylase → activation → increased mobilization of glucose from glycogen
→ Phosphorylation of glycogen synthase → inhibition→ decreased glycogen formation
*takes place in muscle and liver cells
Which amino acids (2) are the target of protein kinase A and protein kinase C?
serine and threonine
Which amino acids (3) are characterized by branched side chains?
branched chain amino acids (BCAA)doesn’t just mean an amino acid with any old branched chain. it refers to
Leucine, Isoleucine, Valine
MN: BCAA help you LIVe!
Which amino acid is the precursor to serotonin and niacin?
tryptophan
what is the PK-LR gene and what happens if there is a mutation causing deficiency of its product
codes for pyruvate kinase expression in the liver and red blood cells. mutation can cause pyruvate kinase deficiency (PKD). in RBCs, this can screw up the Na+/K+ pump (bc it requirers ATP) and cause water to diffuse out of the cell leading to abormal RBC shape and hemolysis (in the spleen)
This is a non-hemoglobin related hemolytic anemia
*the liver is less affected because it has organelles –> can create proteins to replace the low PK and has other means of producing ATP
what is the function of the mitochondrial pyruvate carrier and where is it located
it is embedded into the inner mitochondrial membrane and carries pyruvate to the matrix
For every 1 molecule of NADH that enters the ETC ______(#) protons are transported from the matrix to the intermembrane space
10
a leacteal is
a lymphatic capillary
*carries lipoproteins among other things
which elements in fatty acid metabolism don’t HAVE to be packaged into a micelle and repacked into a chylomichron in order to enter the blood stream
short chain free FAs
medium chain free FAs
glycerol
everything else is too big to pass right through to the blood stream
how do statins work?
- Statin medications inhibit HMG-CoA reductase (HMGCR), an enzyme required for hepatic cholesterol synthesis.
- When cholesterol synthesis is inhibited, the liver upregulates LDL receptors on cells in order to get cholesterol from the LDL in the blood (dietary cholesterol).
- As a result, LDL is removed from the blood and LDL levels are lowered.
*The major apolipoprotein on LDL is ApoB-100. ApoB-100 is found on VLDL, IDL, and LDL. ApoB-100 binds the LDL receptor and mediates endocytosis of LDL.
____________promotes both HMG-CoA reductase transcription and activation by dephosphorylation, while ____________ promotes inactivation by phosphorylation
Insulin promotes both HMG-CoA reductase transcription and activation by dephosphorylation while glucagon promots inactivation by phosphorylation
Diabetics taking exogenous insulin would be expected to have elevated levels of ___________ activity in their hepatocytes.
HMG-CoA reductase activity
this enzyme converts HMG-CoA to mevalonate (and ultimately to cholesterol)
PPP (pentose phosphate pathway)
aka HMP shunt (hexose monophosphate)
what is it for?
The pentose phosphate pathway (also called the hexose monophosphate (HMP) shunt) is a two-phase pathway consisting of an oxidative phase and nonoxidative phase that uses glucose-6-phosphate to produce NADPH and ribose-5-phosphate.
2 NADPH are used
Ribose-5-phosphate is used as a precursor for nucleotide synthesis. The reaction also produces fructose-6-phosphate and glyceraldehyde-3-phosphate, which are used as substrates for glycolysis in the fed state, and for intermediates in gluconeogenesis in the fasting state.
glucose-6-phosphate dehydrogenase (G6PD) -what pathway?
pentose phosphate pathway - converts the 2nd intermediate in glycolysis to
6 -phosphogluconolactone (aka glucono 1,5 lactone-6 phosphate) thereby shunting it to the pentose phosphate pathway aka HMP shunt
what is the last intermediate in common in the PPP before it branches off into two different offshoots of the pathway?
what are the 2 offshoots of the pathway?
- ribulose 5 phosphate
- The two offshoots are
- –> back into glcolysis by prroducing fructose 6 phosphate (the intermediate after G6P)
- –> synthesis of purine and pyrimidine
Collagen is synthesized as a _________
pre-pro-protein, which means it’s not ready for use until it’s modified.
True or False:
Collagen has an alpha helix structure
In collagen, the collagen helix, or type-2 helix, is a major shape in secondary structure. … Due to the high abundance of glycine and proline contents, collagen fails to form a regular α-helix and β-sheet structure. Three left-handed helical strands twist to form a right-handed triple helix.
Describe the biochemistry and clinical features of I-cell disease
- Under normal circumstances GlcNAc phosphotransferase phosphorylates mannose on N-linked glycoproteins, aligning them to the lysosomes. If this enzyme is impaired, the glycoproteins are not targeted to the lysosomes; instead, they are excreted by the cell and into the serum. Lysosomes are then deprived of essential enzymes, and products destined for lysosomal degradation accumulate intracellularly. This causes inclusion-cell disease or I-cell disease.
- Symptoms include motor and developmental delay, coarse facial features, hepatomegaly, immune deficiency, skeletal pathology, hernias, and diastasis recti. The diagnosis can be confirmed by blood tests for lysosomal enzymes (which are elevated) as well as the level of GlcNAc phosphotransferase in leukocytes and in cultured fibroblasts.
Describe the biochemical and clinical signs of chronic hypercorticism
Glucocorticoids (GC) are used to treat different chronic inflammatory and autoimmune disorders, but their prolonged intake can cause hypercorticism with characteristic symptoms, which include weight gain, mood changes, muscle weakness, memory dysfunction, osteoporosis, hyperglycemia, hypertension, immunosuppression, hair loss, and hirsutism. All of these changes are due to a chain of molecular interactions that involve the GC molecule, GC receptors, GC responsive elements, and transcription of target genes (stimulated by GC dimer). Classic GC receptors are intracellular receptors consisting of the hormone-binding domain, variable region, hinge region, and DNA-binding domain, which consists of 2 non-repetitive zinc finger motifs.
*This is the iatrogenic etiology of Cushing Syndrome
what is the MPC
mitochondrial pyruvate carrier
The graph labeled #5 in this diagram is demonstrating what kind of inhibition
substrate excess inhibition
