Biochemistry - Metabolism Flashcards
Pathways with metabolism site occurring in the mitochondria
Fatty acid oxidation (b-ox)
Acetyl CoA production
TCA cycle
Oxidative phosphorylation
Pathways with metabolism site occurring in the cytoplasm
Glycolysis FA synthesis HMP shunt Protein synthesis (RER) Steroid synthesis (SER) Cholesterol synthesis
Pathways where metabolism occurs in both mitochondria and cytoplasm
HUGs take TWO (i.e., both)
Heme synthesis
Urea cycle
Gluconeogenesis
Hexokinase
all tissues other than liver and b-cells of pancreas
Km and Vmax - lower (increased affinity, decreased capacity)
Not induced by insulin
Feedback inhibited by glucose 6-P
Glucokinase
Liver and b-cells in pancreas
Km and Vmas - higher (decreased affinity, increased capacity)
Induced by insulin
Feedback inhibited by fructose 6-P
First step of glycolysis?
Glucose to glucose 6-P
Where is glucose stored at low concentrations? high concentrations?
Tissue (low) and liver (high)
Rate limiting step of glycolysis?
PFK 1
What is occurring in the fed state during regulation by F2,6BP?
Increase insulin, decreased cAMP, decreased protein kinase A, decreased FBPase 2, increased PFK 2, more glycolysis, less gluconeogenesis
What is occurring in the fasting state during regulation by F2,6BP?
Increased glucagon, increased cAMP, increased protein kinase A, decreased PFK 2, increased FBPase 2, more gluconeogensis, less glycolysis
What are the enzymes in the pyruvate dehydrogenase complex? what are their cofactors?
Pyruvate dehydrogenase - TPP (B1 thiamin)
Dihydrolipoyl transacetylase - lipoate, CoA
Dihydrolipoyl dehygrogenase - NAD+, FAD
What happened when there is a pyruvate dehydrogenase complex deficiency?
Causes a buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT)
What is the conversion that the pyruvate dehydrogenase complex is apart of?
Pyruvate -> Acetly CoA
How do you treat pyruvate dehydrogenase complex deficiency?
Increase intake of ketogenic nutrients (high fat content or increase lysine and leucine)
Lysine and Leucine - the onLy pureLy ketogenic amino acids
Findings in pyruvate dehydrogenase complex deficiency?
neurologic defects, lactic acidosis, Increased serum alanine starting in infancy
Pyruvate -> Acetyl CoA produces what products? and how many?
1 NADH
1 CO2
Where do TCA cycle rxns occur?
Mitochondria
What products and how many of each are produced by the TCA cycle?
3 NADH, 1FADH2, 2 CO2, 1 GTP per acetyl CoA = 10 ATP/acetyl CoA (2x everything per glucose)
What substrates are in the Krebs cycle?
Citrate Is Kreb’s Starting Substrate For Making Oxaloacetate
Citrate Isocitrate alpha-Ketoglutarate Succinyl-CoA Succinate Fumarate Malate Oxaloacetate
NADH electrons from glycolysis enter the mitochondria via what shuttle?
Malate-aspartate shuttle or glycerol 3-P shuttle
How many reactions occur in the Kreb’s cycle?
8 reactions
Where does the electron transport chain occur?
Inner membrane of the mitochondrion
How many types of electron carriers comprise the ETC?
4 FMN Fe-S clusters CoQ10 Cytochromes
Which of the electron carriers in the ETC are mobile?
CoQ10 and Cytochrome C
What occurs in Complex I: NADH Dehydrogenase of the ETC?
NADH transfers ions and electrons to FMN. The reduced FMNH2 forms, while NADH is deoxidized to NAD+, which returns to oxidative pathways such as TCA cycle oxidize more substrates
Within complex I, the electrons are transferred to the Fe-S clusters and then to CoQ10
What occurs in Complex II: Succinate Dehydrogenase of the ETC?
Used when FADH2 is generated from the conversion of succinate -> fumarate in the TCA cycle
Electrons from FADH2 are transferred to CoQ10 to yield QH2
This complex has a lower energy level than Complex I so FADH2 enters at a lower energy level here then NADH in complex I
What occurs in Complex III: Coenzyme Q10-Cytochrome c Reductase of the ETC?
The mobile carrier QH2 transfers electrons it has collected from NADH and FADH2 to an Fe-S cluster and then to cytochrome b, the first cytochrome in complex III
From cut b, the electron is transferred to an Fe-S cluster and then to cut c1 and tgeb ti cut c. Each time an Fe3+ ion accepts an electron, it is reduced to Fe2+ and then oxidized back to Fe3+ as the electron is passed on along the chain. Cyt c is another mobile carrier, it moves the electron from complex III to complex IV
What occurs in Complex IV: Cytochrome c Oxidase of the ETC?
electrons are transferred from cytochrome c to cytochrome a, and then to cytochrome a3, the last cytochrome. In the final step of electron transport, electrons and hydrogen ions combine with oxygen (O2) to form water
4H+ + 4e- + O2 -> 2H20
What enzyme converts pyruvate to oxaloacetate in gluconeogenesis? Where does this occur?
Pyruvate carboxylase
Occurs in the mitochondria
What enzyme converts oxaloacetate to phosphoenolpyruvate (PEP)? Where does this occur?
PEP carboxykinase
Occurs in the cytosol
What enzyme converts fructose-1,6-BP to fructose 6-P in gluconeogenesis? Where does this occur?
Fructose 1,6-Bisphosphatase
Occurs in the cytosol
What enzyme converts Glucose 6-P to Glucose in gluconeogenesis? Where does this occur?
Glucose 6-phosphatase
What organ does gluconeogensis primarily occur in?
Liver
From what substrate to substrate is repeated in gluconeogenesis from glycolysis?
PEP to fructose 1,6-P
Odd-chain vs even-chain FAs as a glucose source
odd chain FAs cab enter TCA cycle, undergo gluconeogenesis and serve as a glucose source
even chain FAs cannot produce new glucose, since they yield only acetyl CoA equivalents
What tissue cannot participate in gluconeogenesis and why?
Muscle bc it lacks glucose 6-phosphatase
What is the enzyme responsible for the oxidative reaction for the HMP shunt (pentose phosphate pathway)?
glucose 6-P dehydrogenase
What does the HMP shunt provide a source of?
NADPH from abundantly available glucose 6-P and ribose for nucleotide synthesis and glycolytic intermediates
Where does the HMP shunt occur?
Cytoplasm
What is NADPH necessary for?
It keeps glutathione reduced, which in turn detoxifies free radicles and peroxides
What does decreased NADPH in RBCs lead to?
Hemolytic anemia due to poor RBC defence against oxidizing agents
Essential fructosuria
defect in fructokinase
autosomal recessive
benign, asxs since fructose is not trapped in the cells
fructose appears in blood and urine
Fructose intolerance
hereditary deficiency of aldolase B
autosomal recessive
Fructose-1-P accumulates, causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis
Symptoms present following consumption of fruit, juice, or honey
Sxs: hypoglycemia, jaundice, cirrhosis, vomiting
Tx: decrease intake of both fructose and sucrose (glucose + fructose)
Galactokinase Deficiency
Hereditary deficiency of galactokinase
Galactitol accumulates if galactose is present in diet
Relatively mild condition
autosomal recessive, metabolic dz
Sxs: galactose appears in blood and urine, infantile cataracts. May initially present as failure to track objects or to develop a social smile
