Biochemistry 441 UMKC: Exam 3

what is metabolism?

a series of linked reactions that convert a specific reactant into a specific product

what is the universal currency of free energy?

ATP

the oxidation of what atom is an important source of cellular energy?

carbon

metabolic pathways contain many recurring ______________

motifs

what is catabolism?

reactions that transform fuels into cellular energy

catabolism is _______________ (biosynthetic/degradative)

degradative

fuels (carbohydrates, fats, protein) to CO2 + H2O + Energy is an example of what type of reaction? (catabolic/anabolic/amphibolic)

catabolic

what is anabolism?

reactions that require energy

anabolism is _____________ (biosynthetic/degradative)

biosynthetic

energy (ATP/GTP) + precursors to complex molecules is an example of what type of reaction (catabolic/anabolic/amphibolic)

anabolic

glycolysis and fatty acid beta-oxidation are examples of what type of reaction (catabolic/anabolic/amphibolic)

catabolic

DNA replication and protein synthesis are examples of what type of reaction (catabolic/anabolic/amphibolic)

anabolic

what are amphibolic pathways?

pathways that have dual nature as both catabolic and anabolic pathway

the TCA cycle is an example of what kind of reaction (catabolic/anabolic/amphibolic)

amphibolic

what are the two criteria for the construction of a metabolic pathways

1. the individual reactions must be specific

2. the pathway in total must be thermodynamically favorable

how can one make a thermodynamically unfavorable reaction favorable?

by coupling it to a favorable (more negative ∆G) reaction

what are activated carriers?

biomolecules that store energy in the form of transferable chemical groups

what is the most common activated carrier?

ATP

why is ATP the ideal currency for the cell?

because the phosphate groups are highly unstable and easy to hydrolyze, but the ∆G˚' isn't so negative that it can't hold on to the phosphate group

ATP hydrolysis is thermodynamically ______________ (favorable/unfavorable) but kinetically ___________________ (favorable/unfavorable)

favorable, unfavorable

the more _______________ (oxidized/reduced) a carbon atom is, the _________________ (more/less) free energy is released upon oxidation

reduced, more

fats are a ___________ (more/less) efficient food source than glucose because fats are more _______________ (oxidized/reduced)

more, reduced

which form is the oxidized and which is reduced between NAD+ and NADH?

NAD+ = oxidized

NADH = reduced

which form is the oxidized and which is reduced between FAD and FADH2?

FAD = oxidized

NADH = reduced

what is NADP+

an electron carrier

what is the difference between NADP+ and NAD+?

an additional phosphate group in NADP+

what is coenzyme A?

carrier of acyl groups

why is CoA a good carrier of acyl groups?

because the thiol-ester bond has such a negative ∆G˚' of hydrolysis value

what is homeostasis?

a stable biochemical environment that is maintained by careful regulation of biochemical processes

what is glycolysis?

the breakdown of glucose by enzymes, releasing 2 ATP, 2 pyruvate, and 2 NADH

Is glycolysis aerobic or anaerobic?

anaerobic

what is a general summary of stage one of glycolysis? is ATP required or produced?

stage one involves activating and trapping glucose in the cell to be cleaved into 2 3-carbon molecules

requires ATP

what is a general summary of stage two of glycolysis? is ATP required or produced?

oxidation of the two 3-carbon molecules

ATP produced

if there is an increase in ATP, what happens to the energy charge?

it increases as well

what is the formula for energy charge?

what is the formula for phosphorylation potential?

phosphorylation potential = [ATP] / [ADP] + [Pi]

how do cells regenerate NAD+ for glycolysis?

through further metabolism of pyruvate

what do the 2 anaerobic pathways for pyruvate result in?

ethanol and lactate

what is the intermediate for the transformation of pyruvate to ethanol?

acetaldehyde

how many steps are involved in the transformation of pyruvate to lactate?

1 step

what is the aerobic metabolic process for pyruvate called?

the TCA cycle

what does step one of converting pyruvate to ethanol involve? (what type of reaction)

decarboxylation to acetaldehyde

what does step two of converting pyruvate to ethanol involve? (what type of reaction)

reduction to ethanol

what type of reaction is the transformation of ethanol to lactate?

reduction

where does the transformation of ethanol to lactate usually occur?

in muscle tissue undergoing intense exercise

is there a net redox reaction in the conversion of glucose to ethanol? what about for glucose to lactate?

no net redox for either reaction

what enzyme is the aerobic regeneration of NAD+ catalyzed by?

enzyme pyruvate dehydrogenase

what are the 3 enzymes in glycolysis that catalyze the regulated steps?

hexokinase

phosphofructokinase

pyruvate kinase

what is the primary control in the regulation of glycolysis in muscle cells?

the energy charge of the cell (ATP/AMP ratio)

in glycolysis, what is the influence of ATP and AMP on phosphofructokinase? (muscle cells)

increased ATP/decreased AMP inhibits the enzyme, and the reverse activates it

what is the influence of pH on phosphofructokinase in glycolysis? (muscle cells)

low pH inhibits the enzyme from lactic acid generation

glucose-6-phosphate ______________ (activates/inhibits) hexokinase in glycolysis (muscle cells)

inhibits

what is the influence of ATP on pyruvate kinase in glycolysis (muscle cells)

increased ATP inhibits the enzyme

what is the influence of fructose-1,6-bisphosphate (from PFK) on pyruvate kinase in glycolysis? (muscle cells)

it activates pyruvate kinase

what does the liver do as it relates to glycolysis?

buffers blood glucose concentration

in glycolysis, what is the influence of ATP and AMP on phosphofructokinase? (liver cells)

increased ATP/decreased AMP inhibits the enzyme, and the reverse activates it

what is the influence of pH on phosphofructokinase in glycolysis? (liver cells)

not a factor (no lactate)

what is the influence of citrate on phosphofructokinase in glycolysis? (liver cells)

inhibits PFK

feed forward stimulation by glucose (via F-2,6-BP) __________________ (inhibits/activates) phosphofructokinase

activates

what is the enzyme similar to hexokinase in the liver?

glucokinase

when is glucokinase active?

when glucose levels are high

what is the influence of alanine on pyruvate kinase in glycolysis? (liver cells)

it inhibits pyruvate kinase

Where is the major site of gluconeogenesis? where else can it occur?

liver

kidneys

what is the fate of fructose in the liver?

it is metabolized by the fructose-1-phosphate pathway

where in the cell does the first step of gluconeogenesis occur?

mitochondria

where in the cell does most of gluconeogenesis occur?

cytosol

where does the 11th step of gluconeogenesis occur?

endoplasmic reticulum

what are the enzymes in gluconeogenesis that catalyze the bypassing of the irreversible steps in gycolysis? (Hint: there are 4)

pyruvate carboxylase

pep carboxykinase

fructose-1,6-bisphosphatase

glucose-6-phosphatase

how and where is pyruvate converted to pep?

pyruvate is carboxylated to oxaloacetate (oaa) in the mitochondrial matrix, then oaa is reduced to malate by NADH and shuttled across to the cytoplasm. from there it is oxidized back into oaa. oaa is decarboxylated into pep.

what is glucose-6-phosphate usually converted to (when not creating glucose)?

glycogen

when energy is needed, what happens to the ATP/AMP ratio?

it is lowered

glucagon levels _______________ (rise/fall) as blood glucose concentrations fall. what does this process result in?

rise. results in formation of cAMP

what is the purpose of cAMP?

activates protein kinase A, the enzyme that phosphorylates the bifunctional enzyme that regulates fructose-2,6-bisphosphate

what enzymes are regulated in order to buffer blood glucose concentrations? (Hint: One is from glycolysis and one is from gluconeogenesis)

PFK & Fructose-1,6-Bisphosphatase

What is fructose 2,6-bisphosphate? what does it do?

an allosteric regulator

-activates phosphofructokinase

-inhibits fructose 1,6-biphosphatase

what is the production of fructose-2,6-bisphosphate catalyzed by?

PFK2

what is the degradation of fructose-2,6-bisphosphate catalyzed by?

fructose-2,6-bisphosphatase

where can PFK2 and F-2,6-BPase be found?

on the same protein

how does the bifunctional enzyme that includes PFK2 and F-2,6-BPase get regulated?

it regulates itself via phosphorylation of a key serine residue in response to the hormone glucagon that tracks blood glucose concentrations

what stimulates phosphoprotein phosphatase?

rising levels of fructose-6-phosphate and insulin

what does phosphoprotein phosphatase do?

removes phosphorylation from the bifunctional enzyme, thereby activating PFK2 and activating PFK/inhibiting F-1,6-BPase

what happens to lactate in highly oxygenated cells such as cardiac muscle?

it is oxidized to pyruvate and metabolized through the TCA cycle

what is the Cori cycle?

A process in the liver that regenerates glucose from lactate released by muscles

what happens to lactate in the liver?

oxidized back to pyruvate as a precursor for gluconeogenesis

what amino acid is a precursor for liver gluconeogenesis?

alanine

what molecule links glycolysis to the citric acid cycle?

pyruvate dehydrogenase

how many steps are in the TCA cycle?

8

Is the TCA cycle aerobic or anaerobic?

aerobic

Does the TCA cycle require oxygen?

yes, indirectly

how many GTP are produced in the TCA cycle?

1

how many NADH molecules are produced in the TCA cycle?

3

how many FADH2 molecules are produced in the TCA cycle?

1

what is required to convert pyruvate to acetyl-coA?

3 enzymes and 5 cofactors

what are the 3 enzymes catalyzing the conversion of pyruvate to acetyl-coA collectively called?

the pyruvate dehydrogenase complex

true/false - pyruvate can be made from acetyl coA

false. the reaction converting pyruvate to acetyl coA is irreversible

what are the two fates of acetyl coA

metabolism in the TCA cycle

incorporation into fatty acids

what is a synthase?

an enzyme that catalyzes a synthetic reaction in which two units are joined usually without the direct participation of any NTPs

what is a synthetase?

utilizes NTP(s) to conduct synthesis

How many ATP equivalent molecules are formed for each acetyl-coA oxidized? where do they come from?

10

2.5 from NADH (x3)

1.5 from FADH2

1 from GTP

what are the enzymes that mark the key regulation steps in the TCA cycle (Hint: there are 3)

pyruvate dehydrogenase

isocitrate dehydrogenase

ketoglutarate dehydrogenase